PMID- 30926528 OWN - NLM STAT- In-Data-Review LR - 20190420 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 143 DP - 2019 May TI - Cardiovascular events with PCSK9 inhibitors: an updated meta-analysis of randomised controlled trials. PG - 143-150 LID - S1043-6618(18)31849-8 [pii] LID - 10.1016/j.phrs.2019.03.021 [doi] AB - The therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors efficiently reduces plasma cholesterol levels, which has been recently associated with improvement in cardiovascular outcomes. This meta-analysis aimed at investigating the safety and efficacy of treatment with the clinically available anti-PCSK9 monoclonal antibodies (mAbs) in all published randomized clinical trials (RCTs), updating the available results with the recently published ODYSSEY OUTCOMES trial. Data search was carried out using PubMed/MEDLINE and EMBASE (inception - January 2019). Inclusion criteria were: (1) phase 2 or 3 RCTs; (2) comparing anti-PCSK9 mAbs (specifically evolocumab and alirocumab) with placebo; (3) with effects on outcomes reported; (4) with treatment duration longer than 8 weeks. Odds ratios (ORs) with 95% CIs were used as summary statistics. We pooled the estimates by using both the DerSimonian & Laird method (random-effects model). Between-study heterogeneity was tested by Cochrane's Q test and measured with the I2 statistics. Twenty-eight RCTs comprising 62,281 participants (33,204 in the mAb arm, 29,077 in the placebo arm) were included in the meta-analysis. The treatment follow-up ranged from 8 weeks up to 208 weeks. Overall, no significant difference in all-cause mortality was observed between the two groups (OR 0.93 [95% CI, 0.85-1.03]). The treatment with an anti-PCSK9 mAb was associated with a significant reduction of CV events compared with placebo (OR 0.83 [95% CI, 0.78-0.87]), being the FOURIER and ODYSSEY OUTCOMES studies the major contributors. Both myocardial infarction and stroke were significantly reduced following the treatment with an anti-PCSK9 mAb. No significant difference was observed in cardiovascular mortality (OR 0.94 [95% CI, 0.83-1.07]). The incidence of serious adverse events was similar in the two groups (OR: 0.95, [95% CI, 0.91-0.99]). Thus, the pharmacological approach with anti-PCSK9 mAbs significantly and safely improves cardiovascular outcomes. Despite that, the pooled analysis failed to show a significant cardiovascular mortality benefit with anti-PCSK9 mAb treatment, suggesting that specific longer-term studies are warranted to address this issue. We suggest that the observed delay between the rapid effect on plasma cholesterol levels and the emergence of the clinical benefit, observed both in FOURIER and ODYSSEY OUTCOMES trials, might explain this finding. CI - Copyright (c) 2019. Published by Elsevier Ltd. FAU - Casula, Manuela AU - Casula M AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Olmastroni, Elena AU - Olmastroni E AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Boccalari, Mezio T AU - Boccalari MT AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article DEP - 20190326 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 OTO - NOTNLM OT - Cardiovascular events OT - Cardiovascular mortality OT - Monoclonal antibodies OT - PCSK9 EDAT- 2019/03/31 06:00 MHDA- 2019/03/31 06:00 CRDT- 2019/03/31 06:00 PHST- 2018/11/23 00:00 [received] PHST- 2019/02/15 00:00 [revised] PHST- 2019/03/25 00:00 [accepted] PHST- 2019/03/31 06:00 [pubmed] PHST- 2019/03/31 06:00 [medline] PHST- 2019/03/31 06:00 [entrez] AID - S1043-6618(18)31849-8 [pii] AID - 10.1016/j.phrs.2019.03.021 [doi] PST - ppublish SO - Pharmacol Res. 2019 May;143:143-150. doi: 10.1016/j.phrs.2019.03.021. Epub 2019 Mar 26. PMID- 30972066 OWN - NLM STAT- In-Data-Review LR - 20190414 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Identification of AnnexinA1 as an Endogenous Regulator of RhoA, and Its Role in the Pathophysiology and Experimental Therapy of Type-2 Diabetes. PG - 571 LID - 10.3389/fimmu.2019.00571 [doi] AB - Annexin A1 (ANXA1) is an endogenously produced anti-inflammatory protein, which plays an important role in the pathophysiology of diseases associated with chronic inflammation. We demonstrate that patients with type-2 diabetes have increased plasma levels of ANXA1 when compared to normoglycemic subjects. Plasma ANXA1 positively correlated with fatty liver index and elevated plasma cholesterol in patients with type-2 diabetes, suggesting a link between aberrant lipid handling, and ANXA1. Using a murine model of high fat diet (HFD)-induced insulin resistance, we then investigated (a) the role of endogenous ANXA1 in the pathophysiology of HFD-induced insulin resistance using ANXA1(-/-) mice, and (b) the potential use of hrANXA1 as a new therapeutic approach for experimental diabetes and its microvascular complications. We demonstrate that: (1) ANXA1(-/-) mice fed a HFD have a more severe diabetic phenotype (e.g., more severe dyslipidemia, insulin resistance, hepatosteatosis, and proteinuria) compared to WT mice fed a HFD; (2) treatment of WT-mice fed a HFD with hrANXA1 attenuated the development of insulin resistance, hepatosteatosis and proteinuria. We demonstrate here for the first time that ANXA1(-/-) mice have constitutively activated RhoA. Interestingly, diabetic mice, which have reduced tissue expression of ANXA1, also have activated RhoA. Treatment of HFD-mice with hrANXA1 restored tissue levels of ANXA1 and inhibited RhoA activity, which, in turn, resulted in restoration of the activities of Akt, GSK-3beta and endothelial nitric oxide synthase (eNOS) secondary to re-sensitization of IRS-1 signaling. We further demonstrate in human hepatocytes that ANXA1 protects against excessive mitochondrial proton leak by activating FPR2 under hyperglycaemic conditions. In summary, our data suggest that (a) ANXA1 is a key regulator of RhoA activity, which restores IRS-1 signal transduction and (b) recombinant human ANXA1 may represent a novel candidate for the treatment of T2D and/or its complications. FAU - Purvis, Gareth S D AU - Purvis GSD AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. FAU - Collino, Massimo AU - Collino M AD - Department of Drug Science and Technology, University of Turin, Turin, Italy. FAU - Loiola, Rodrigo A AU - Loiola RA AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, Milan, Italy. FAU - Chiazza, Fausto AU - Chiazza F AD - Department of Drug Science and Technology, University of Turin, Turin, Italy. FAU - Brovelli, Martina AU - Brovelli M AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, Milan, Italy. AD - Centro SISA per lo studio del'Aterosclerosi, Bassini Hospital, Lombardy, Italy. FAU - Sheikh, Madeeha H AU - Sheikh MH AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. FAU - Collotta, Debora AU - Collotta D AD - Department of Drug Science and Technology, University of Turin, Turin, Italy. FAU - Cento, Alessia AU - Cento A AD - Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. FAU - Mastrocola, Raffaella AU - Mastrocola R AD - Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. FAU - Aragno, Manuela AU - Aragno M AD - Department of Molecular Biotechnology and Sciences for the Health, University of Turin, Turin, Italy. FAU - Cutrin, Juan C AU - Cutrin JC AD - Department of Molecular Biotechnology and Sciences for the Health, University of Turin, Turin, Italy. FAU - Reutelingsperger, Chris AU - Reutelingsperger C AD - Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, Maastricht, Netherlands. FAU - Grigore, Liliana AU - Grigore L AD - Centro SISA per lo studio del'Aterosclerosi, Bassini Hospital, Lombardy, Italy. AD - IRCCS Multimedica, Lombardy, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, Milan, Italy. FAU - Yaqoob, Magdi M AU - Yaqoob MM AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, Milan, Italy. AD - Centro SISA per lo studio del'Aterosclerosi, Bassini Hospital, Lombardy, Italy. FAU - Solito, Egle AU - Solito E AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. AD - Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita Degli Studi di Napoli "Federico II", Naples, Italy. FAU - Thiemermann, Christoph AU - Thiemermann C AD - Department of Translational Medicine and Therapeutics, Bart's and The London School of Medicine and Dentistry, The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. LA - eng PT - Journal Article DEP - 20190327 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC6446914 OTO - NOTNLM OT - Annexin A1 OT - Rho A OT - hepatosteatosis OT - metabolism OT - nephropathy OT - type-2 diabetes EDAT- 2019/04/12 06:00 MHDA- 2019/04/12 06:00 CRDT- 2019/04/12 06:00 PHST- 2019/01/11 00:00 [received] PHST- 2019/03/04 00:00 [accepted] PHST- 2019/04/12 06:00 [entrez] PHST- 2019/04/12 06:00 [pubmed] PHST- 2019/04/12 06:00 [medline] AID - 10.3389/fimmu.2019.00571 [doi] PST - epublish SO - Front Immunol. 2019 Mar 27;10:571. doi: 10.3389/fimmu.2019.00571. eCollection 2019. PMID- 30888513 OWN - NLM STAT- In-Data-Review LR - 20190329 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 19 IP - 5 DP - 2019 Mar 19 TI - The Interconnection Between Immuno-Metabolism, Diabetes, and CKD. PG - 21 LID - 10.1007/s11892-019-1143-4 [doi] AB - PURPOSE OF REVIEW: Metabolic reprogramming is increasingly recognized as an essential trait of functional activation of immune cells. Here, we describe the link between immuno-metabolism, diabetes, and diabetic nephropathy. RECENT FINDINGS: Crosstalk between cellular metabolic functions and immune activation occurs when plasma levels of glucose, triglycerides, and free fatty acids increase, thus promoting systemic low-grade inflammation that further boosts the development of metabolic complications. In the long run, this settles an "apparent paradox," where, despite excessive inflammation, the immune system is suppressed, further promoting progression to end-stage renal disease (ESRD) and predisposing to premature deaths from infections and cardiovascular diseases. Reviewing the effects of diabetes treatments on immuno-inflammatory responses suggests that the benefit of these drugs might extend beyond the simple control of glucose homeostasis. Hyperglycemia and dyslipidemia correlate with enhancement of the immuno-inflammatory response that can promote and worsen metabolic diseases and support the progression toward ESRD. The identification of cellular checkpoints that modulate the immuno-metabolic machinery of immune cells opens new venues for metabolic drugs. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. AD - SISA Centre, Bassini Hospital, 20092, Cinisello Balsamo, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. AD - IRCSS Multimedica, 20138, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. danilo.norata@unimi.it. AD - SISA Centre, Bassini Hospital, 20092, Cinisello Balsamo, Italy. danilo.norata@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20190319 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 OTO - NOTNLM OT - Diabetes OT - Immune response OT - Kidney disease OT - Metabolism EDAT- 2019/03/20 06:00 MHDA- 2019/03/20 06:00 CRDT- 2019/03/20 06:00 PHST- 2019/03/20 06:00 [entrez] PHST- 2019/03/20 06:00 [pubmed] PHST- 2019/03/20 06:00 [medline] AID - 10.1007/s11892-019-1143-4 [doi] AID - 10.1007/s11892-019-1143-4 [pii] PST - epublish SO - Curr Diab Rep. 2019 Mar 19;19(5):21. doi: 10.1007/s11892-019-1143-4. PMID- 30865797 OWN - NLM STAT- MEDLINE DCOM- 20190325 LR - 20190325 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 380 IP - 11 DP - 2019 Mar 14 TI - Mendelian Randomization Study of ACLY and Cardiovascular Disease. PG - 1033-1042 LID - 10.1056/NEJMoa1806747 [doi] AB - BACKGROUND: ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear. METHODS: We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (ACLY) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer. RESULTS: A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The ACLY and HMGCR scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confidence interval [CI], 0.78 to 0.87; P = 4.0x10(-14)) for the ACLY score and 0.836 (95% CI, 0.81 to 0.87; P = 3.9x10(-19)) for the HMGCR score. Neither lifelong genetic inhibition of ATP citrate lyase nor lifelong genetic inhibition of HMGCR was associated with an increased risk of cancer. CONCLUSIONS: Genetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.). CI - Copyright (c) 2019 Massachusetts Medical Society. FAU - Ference, Brian A AU - Ference BA AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Ray, Kausik K AU - Ray KK AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Catapano, Alberico L AU - Catapano AL AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Ference, Thatcher B AU - Ference TB AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Burgess, Stephen AU - Burgess S AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Neff, David R AU - Neff DR AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Oliver-Williams, Clare AU - Oliver-Williams C AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Wood, Angela M AU - Wood AM AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Butterworth, Adam S AU - Butterworth AS AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Di Angelantonio, Emanuele AU - Di Angelantonio E AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Danesh, John AU - Danesh J AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Kastelein, John J P AU - Kastelein JJP AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). FAU - Nicholls, Stephen J AU - Nicholls SJ AD - From the Centre for Naturally Randomized Trials (B.A.F., T.B.F.), Medical Research Council, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care (B.A.F., S.B., C.O.-W., A.M.W., A.S.B., E.D.A., J.D.), Medical Research Council Biostatistics Unit (S.B.), and NIHR Blood and Transplant Research Unit in Donor Health and Genomics (A.S.B., E.D.A., J.D.), University of Cambridge, Cambridge, and Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London (K.K.R.) - all in the United Kingdom; the Department of Pharmacologic and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milan (A.L.C.); Michigan State University, East Lansing (D.R.N.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); and Monash University, Clayton, VIC, Australia (S.J.N.). LA - eng GR - Investigator Initiated Grant Award/NIHR Cambridge Biomedical Research Centre/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Cholesterol, LDL) RN - 0 (Dicarboxylic Acids) RN - 0 (Fatty Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoproteins) RN - 0 (Membrane Proteins) RN - 0 (NPC1L1 protein, human) RN - 0 (Triglycerides) RN - 1EJ6Z6Q368 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) RN - EC 1.1.1.- (HMGCR protein, human) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) RN - EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase) SB - AIM SB - IM MH - ATP Citrate (pro-S)-Lyase/antagonists & inhibitors/*genetics MH - Cardiovascular Diseases/*genetics MH - Cholesterol, LDL/*blood MH - Diabetes Mellitus/genetics MH - Dicarboxylic Acids/pharmacology/therapeutic use MH - Fatty Acids/pharmacology/therapeutic use MH - Female MH - *Genetic Predisposition to Disease MH - Humans MH - Hydroxymethylglutaryl CoA Reductases/*genetics MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use MH - Hypercholesterolemia/drug therapy MH - Hypolipidemic Agents/pharmacology/therapeutic use MH - Lipoproteins/blood MH - Male MH - Membrane Proteins/genetics MH - *Mendelian Randomization Analysis MH - Middle Aged MH - Neoplasms/genetics MH - Odds Ratio MH - Risk MH - Triglycerides/blood EDAT- 2019/03/14 06:00 MHDA- 2019/03/26 06:00 CRDT- 2019/03/14 06:00 PHST- 2019/03/14 06:00 [entrez] PHST- 2019/03/14 06:00 [pubmed] PHST- 2019/03/26 06:00 [medline] AID - 10.1056/NEJMoa1806747 [doi] PST - ppublish SO - N Engl J Med. 2019 Mar 14;380(11):1033-1042. doi: 10.1056/NEJMoa1806747. PMID- 30865796 OWN - NLM STAT- MEDLINE DCOM- 20190325 LR - 20190325 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 380 IP - 11 DP - 2019 Mar 14 TI - Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. PG - 1022-1032 LID - 10.1056/NEJMoa1803917 [doi] AB - BACKGROUND: Short-term studies have shown that bempedoic acid, an inhibitor of ATP citrate lyase, reduces levels of low-density lipoprotein (LDL) cholesterol. Data are limited regarding the safety and efficacy of bempedoic acid treatment in long-term studies involving patients with hypercholesterolemia who are receiving guideline-recommended statin therapy. METHODS: We conducted a randomized, controlled trial involving patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. Patients had to have an LDL cholesterol level of at least 70 mg per deciliter while they were receiving maximally tolerated statin therapy with or without additional lipid-lowering therapy. (Maximally tolerated statin therapy was defined as the highest intensity statin regimen that a patient was able to maintain, as determined by the investigator.) Patients were randomly assigned in a 2:1 ratio to receive bempedoic acid or placebo. The primary end point was safety, and the principal secondary end point (principal efficacy end point) was the percentage change in the LDL cholesterol level at week 12 of 52 weeks. RESULTS: The trial involved 2230 patients, of whom 1488 were assigned to receive bempedoic acid and 742 to receive placebo. The mean (+/-SD) LDL cholesterol level at baseline was 103.2+/-29.4 mg per deciliter. The incidence of adverse events (1167 of 1487 patients [78.5%] in the bempedoic acid group and 584 of 742 [78.7%] in the placebo group) and serious adverse events (216 patients [14.5%] and 104 [14.0%], respectively) did not differ substantially between the two groups during the intervention period, but the incidence of adverse events leading to discontinuation of the regimen was higher in the bempedoic acid group than in the placebo group (162 patients [10.9%] vs. 53 [7.1%]), as was the incidence of gout (18 patients [1.2%] vs. 2 [0.3%]). At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter, representing a change of -16.5% from baseline (difference vs. placebo in change from baseline, -18.1 percentage points; 95% confidence interval, -20.0 to -16.1; P<0.001). Safety and efficacy findings were consistent, regardless of the intensity of background statin therapy. CONCLUSIONS: In this 52-week trial, bempedoic acid added to maximally tolerated statin therapy did not lead to a higher incidence of overall adverse events than placebo and led to significantly lower LDL cholesterol levels. (Funded by Esperion Therapeutics; CLEAR Harmony ClinicalTrials.gov number, NCT02666664.). CI - Copyright (c) 2019 Massachusetts Medical Society. FAU - Ray, Kausik K AU - Ray KK AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Bays, Harold E AU - Bays HE AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Catapano, Alberico L AU - Catapano AL AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Lalwani, Narendra D AU - Lalwani ND AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Bloedon, LeAnne T AU - Bloedon LT AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Sterling, Lulu R AU - Sterling LR AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Robinson, Paula L AU - Robinson PL AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). FAU - Ballantyne, Christie M AU - Ballantyne CM AD - From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). CN - CLEAR Harmony Trial LA - eng SI - ClinicalTrials.gov/NCT02666664 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Apolipoproteins B) RN - 0 (Cholesterol, LDL) RN - 0 (Dicarboxylic Acids) RN - 0 (Fatty Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptide Fragments) RN - 0 (apolipoprotein B (3304-3317)) RN - 1EJ6Z6Q368 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) RN - 9007-41-4 (C-Reactive Protein) RN - 97C5T2UQ7J (Cholesterol) RN - EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase) SB - AIM SB - IM CIN - N Engl J Med. 2019 Mar 14;380(11):1076-1079. PMID: 30865805 MH - ATP Citrate (pro-S)-Lyase/antagonists & inhibitors MH - Aged MH - Apolipoproteins B/blood MH - C-Reactive Protein/analysis MH - Cholesterol/blood MH - Cholesterol, LDL/*blood MH - Dicarboxylic Acids/adverse effects/*therapeutic use MH - Drug Therapy, Combination MH - Fatty Acids/adverse effects/*therapeutic use MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypercholesterolemia/blood/*drug therapy MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Peptide Fragments/blood MH - Treatment Outcome IR - Aazami H FIR - Aazami, Hessam IR - Akhtar A FIR - Akhtar, Asif IR - Ballantyne CM FIR - Ballantyne, Christie Mitchell IR - Baum S FIR - Baum, Seth IR - Bays HE FIR - Bays, Harold E IR - Bertolet B FIR - Bertolet, Barry IR - Bloom SA FIR - Bloom, Stephen A IR - Boffetti PF FIR - Boffetti, Paul F IR - Brown A FIR - Brown, Alan IR - Butman SM FIR - Butman, Samuel M IR - Cannon KD FIR - Cannon, Kevin D IR - Case C FIR - Case, Christopher IR - Claxton E Jr FIR - Claxton, Edmund Jr IR - Collins JF FIR - Collins, John F IR - Dahl CF FIR - Dahl, Charles F IR - Desai PV FIR - Desai, Pratik V IR - Doyle TP FIR - Doyle, Timothy P IR - Eilerman BS FIR - Eilerman, Bradley S IR - Erickson BR FIR - Erickson, Bernard R IR - Gessler CJ Jr FIR - Gessler, Carl J Jr IR - Halpern SW FIR - Halpern, Stephen W IR - Henderson DA FIR - Henderson, David A IR - Karim AH FIR - Karim, Amin Haji IR - Lederman SN FIR - Lederman, Samuel N IR - Lieber IH FIR - Lieber, Ira H IR - Lillo JL FIR - Lillo, Joseph Leonard IR - Mahal SS FIR - Mahal, Sharan S IR - Malhotra V FIR - Malhotra, Vinay IR - Malik AZ FIR - Malik, Amir Z IR - Maniscalco B FIR - Maniscalco, Benedict IR - McGuinn WP 2nd FIR - McGuinn, William P 2nd IR - McKenney JM FIR - McKenney, James M IR - Melvin EJ FIR - Melvin, Eric J IR - Prasad Potu R FIR - Prasad Potu, Ranganatha IR - Prasada S FIR - Prasada, Sudhir IR - Pritchard JC FIR - Pritchard, James C IR - Reyna J FIR - Reyna, Javier IR - Rizk MM FIR - Rizk, Maged M IR - Robinson JG FIR - Robinson, Jennifer G IR - Rozeman P FIR - Rozeman, Phillip IR - Rubino J FIR - Rubino, John IR - Sampognaro GC FIR - Sampognaro, Gregory C IR - Suneja R FIR - Suneja, Randeep IR - Thompson PD FIR - Thompson, Paul D IR - Weinstein DL FIR - Weinstein, Debra L IR - Woolf K FIR - Woolf, Kevin IR - Zarate JC FIR - Zarate, Juan C IR - Zhang W FIR - Zhang, Wenwu IR - Bakbak A FIR - Bakbak, Asaad IR - Cha J FIR - Cha, James IR - Cheema A FIR - Cheema, Asim IR - Constance C FIR - Constance, Christian IR - Deslongchamps F FIR - Deslongchamps, Francois IR - Gaudet D FIR - Gaudet, Daniel IR - Hartleib MC FIR - Hartleib, Michael C IR - Kouz S FIR - Kouz, Simon IR - Ricci JA FIR - Ricci, Joseph A IR - Robinson S FIR - Robinson, Simon IR - Savard D FIR - Savard, Daniel IR - St-Amour E FIR - St-Amour, Eric IR - Tardif JC FIR - Tardif, Jean-Claude IR - Banach M FIR - Banach, Maciej IR - Blach E FIR - Blach, Elzbieta IR - Bryniarski L FIR - Bryniarski, Leszek IR - Cesarz M FIR - Cesarz, Marek IR - Chmielak Z FIR - Chmielak, Zbigniew IR - Czernecka E FIR - Czernecka, Ewa IR - Konieczny M FIR - Konieczny, Marek IR - Krzykowska J FIR - Krzykowska, Jolanta IR - Krzyzagorska E FIR - Krzyzagorska, Ewa IR - Leksycka A FIR - Leksycka, Agata IR - Lysek R FIR - Lysek, Roman IR - Mordaka R FIR - Mordaka, Robert IR - Rozpondek P FIR - Rozpondek, Piotr IR - Sidorowicz-Bialynicka A FIR - Sidorowicz-Bialynicka, Anna IR - Wojewoda P FIR - Wojewoda, Pawel IR - Woznicka-Leskiewicz L FIR - Woznicka-Leskiewicz, Lucyna IR - Ross H FIR - Ross, Holly IR - Blagden MD FIR - Blagden, Mark D IR - Huong Y FIR - Huong, Yieng IR - Fiore G FIR - Fiore, Gieseppe IR - Ivan P FIR - Ivan, Paul IR - Kondagunta VH FIR - Kondagunta, Venkata H IR - Poterajilo A FIR - Poterajilo, Anton IR - Rayman G FIR - Rayman, Gerry IR - Sathyapalan T FIR - Sathyapalan, Thozhukat IR - Sharma R FIR - Sharma, Rajiv IR - Thomas H FIR - Thomas, Hawys IR - Wong YK FIR - Wong, Yuk-Ki IR - Wright AT FIR - Wright, Anthony T IR - Amoroso G FIR - Amoroso, Giovanni IR - Bartels GL FIR - Bartels, Gerard L IR - Hermans WR FIR - Hermans, Walter R IR - Karalis I FIR - Karalis, Ioannis IR - Nawaz A FIR - Nawaz, Aneqqa IR - Rojas Lingan GM FIR - Rojas Lingan, Gloria M IR - Smits PC FIR - Smits, Peter C IR - Stroes E FIR - Stroes, Erik IR - Troquay RP FIR - Troquay, Roel P IR - van Bemmel BM FIR - van Bemmel, Bastiaan M IR - van Kempen WW FIR - van Kempen, Willem W IR - van Kesteren HAM FIR - van Kesteren, Henricus Arnoldus M IR - Axthelm C FIR - Axthelm, Christoph IR - Becker B FIR - Becker, Bernd IR - Birkenfeld AL FIR - Birkenfeld, Andreas L IR - Contzen C FIR - Contzen, Christel IR - Hartard M FIR - Hartard, Manfred IR - Konig HJ FIR - Konig, Hans-Joachim IR - Rinke A FIR - Rinke, Andrea IR - Schiefke I FIR - Schiefke, Ingolf IR - Sigal H FIR - Sigal, Helena IR - Taeschner H FIR - Taeschner, Heidrun IR - Vismane L FIR - Vismane, Liana EDAT- 2019/03/14 06:00 MHDA- 2019/03/26 06:00 CRDT- 2019/03/14 06:00 PHST- 2019/03/14 06:00 [entrez] PHST- 2019/03/14 06:00 [pubmed] PHST- 2019/03/26 06:00 [medline] AID - 10.1056/NEJMoa1803917 [doi] PST - ppublish SO - N Engl J Med. 2019 Mar 14;380(11):1022-1032. doi: 10.1056/NEJMoa1803917. PMID- 30859179 OWN - NLM STAT- Publisher LR - 20190312 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) DP - 2019 Mar 12 TI - Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity. LID - cvz068 [pii] LID - 10.1093/cvr/cvz068 [doi] AB - AIM: Low-grade chronic inflammation characterizes obesity and metabolic syndrome. Here we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity. METHODS AND RESULTS: PTX3 deficiency in mice fed a high fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with the improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared to non-carriers. CONCLUSIONS: Our results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author(s) 2019. For permissions please email: journals.permissions@oup.com. FAU - Bonacina, F AU - Bonacina F AD - Department of Excellence of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Moregola, A AU - Moregola A AD - Department of Excellence of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Porte, R AU - Porte R AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. FAU - Baragetti, A AU - Baragetti A AD - Department of Excellence of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - Centro SISA per lo Studio dell'Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy. FAU - Bonavita, E AU - Bonavita E AD - Cancer Inflammation and Immunity Group, CRUK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK. FAU - Salatin, A AU - Salatin A AD - Department of Excellence of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Grigore, L AU - Grigore L AD - Centro SISA per lo Studio dell'Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy. AD - IRCSS Multimedica, Milan, Italy. FAU - Pellegatta, F AU - Pellegatta F AD - Centro SISA per lo Studio dell'Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy. AD - IRCSS Multimedica, Milan, Italy. FAU - Molgora, M AU - Molgora M AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. FAU - Sironi, M AU - Sironi M AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. FAU - Barbati, E AU - Barbati E AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. FAU - Mantovani, A AU - Mantovani A AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. AD - Humanitas University Rozzano, Italy. FAU - Bottazzi, B AU - Bottazzi B AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. FAU - Catapano, A L AU - Catapano AL AD - Department of Excellence of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - IRCSS Multimedica, Milan, Italy. FAU - Garlanda, C AU - Garlanda C AD - IRCC Humanitas Clinical and Research Center, Rozzano, Italy. AD - Humanitas University Rozzano, Italy. FAU - Norata, G D AU - Norata GD AD - Department of Excellence of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - Centro SISA per lo Studio dell'Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy. LA - eng PT - Journal Article DEP - 20190312 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 EDAT- 2019/03/13 06:00 MHDA- 2019/03/13 06:00 CRDT- 2019/03/13 06:00 PHST- 2018/08/01 00:00 [received] PHST- 2019/02/25 00:00 [revised] PHST- 2019/01/23 00:00 [revised] PHST- 2019/03/04 00:00 [accepted] PHST- 2019/03/13 06:00 [entrez] PHST- 2019/03/13 06:00 [pubmed] PHST- 2019/03/13 06:00 [medline] AID - 5374872 [pii] AID - 10.1093/cvr/cvz068 [doi] PST - aheadofprint SO - Cardiovasc Res. 2019 Mar 12. pii: 5374872. doi: 10.1093/cvr/cvz068. PMID- 30629143 OWN - NLM STAT- In-Data-Review LR - 20190226 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 115 IP - 3 DP - 2019 Mar 1 TI - Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies. PG - 510-518 LID - 10.1093/cvr/cvz003 [doi] AB - Since the discovery of the role of proprotein convertase subtilisin kexin 9 (PCSK9) in the regulation of low-density lipoprotein cholesterol (LDL-C) in 2003, a paradigm shift in the treatment of hypercholesterolaemia has occurred. The PCSK9 secreted into the circulation is a major downregulator of the low-density lipoprotein receptor (LDLR) protein, as it chaperones it to endosomes/lysosomes for degradation. Humans with loss-of-function of PCSK9 exhibit exceedingly low levels of LDL-C and are protected from atherosclerosis. As a consequence, innovative strategies to modulate the levels of PCSK9 have been developed. Since 2015 inhibitory monoclonal antibodies (evolocumab and alirocumab) are commercially available. When subcutaneously injected every 2-4 weeks, they trigger a approximately 60% LDL-C lowering and a 15% reduction in the risk of cardiovascular events. Another promising approach consists of a liver-targetable specific PCSK9 siRNA which results in approximately 50-60% LDL-C lowering that lasts up to 6 months (Phases II-III clinical trials). Other strategies under consideration include: (i) antibodies targeting the C-terminal domain of PCSK9, thereby inhibiting the trafficking of PCSK9-LDLR to lysosomes; (ii) small molecules that either prevent PCSK9 binding to the LDLR, its trafficking to lysosomes or its secretion from cells; (iii) complete silencing of PCSK9 by CRISPR-Cas9 strategies; (iv) PCSK9 vaccines that inhibit the activity of circulating PCSK9. Time will tell whether other strategies can be as potent and safe as monoclonal antibodies to lower LDL-C levels. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author(s) 2019. For permissions, please email: journals.permissions@oup.com. FAU - Seidah, Nabil G AU - Seidah NG AD - Laboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute (IRCM; Affiliated to the University of Montreal), Montreal, QC H2W1R7, Canada. FAU - Prat, Annik AU - Prat A AD - Laboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute (IRCM; Affiliated to the University of Montreal), Montreal, QC H2W1R7, Canada. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - IRCCS MultiMedica, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS MultiMedica, Milan, Italy. AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 PMC - PMC6383053 OTO - NOTNLM OT - Gene silencing OT - LDL-C OT - Monoclonal antibodies OT - PCSK9 EDAT- 2019/01/11 06:00 MHDA- 2019/01/11 06:00 CRDT- 2019/01/11 06:00 PMCR- 2020/03/01 00:00 PHST- 2018/10/31 00:00 [received] PHST- 2018/12/06 00:00 [revised] PHST- 2019/01/05 00:00 [accepted] PHST- 2020/03/01 00:00 [pmc-release] PHST- 2019/01/11 06:00 [pubmed] PHST- 2019/01/11 06:00 [medline] PHST- 2019/01/11 06:00 [entrez] AID - 5284912 [pii] AID - 10.1093/cvr/cvz003 [doi] PST - ppublish SO - Cardiovasc Res. 2019 Mar 1;115(3):510-518. doi: 10.1093/cvr/cvz003. PMID- 30545250 OWN - NLM STAT- In-Data-Review LR - 20190318 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 26 IP - 5 DP - 2019 Mar TI - Increasing high-density lipoprotein cholesterol levels for cardiovascular benefit: The end of a dream? PG - 531-532 LID - 10.1177/2047487318820976 [doi] FAU - Pirillo, Angela AU - Pirillo A AD - 1 Center for the Study of Atherosclerosis, E. Bassini Hospital, Italy. AD - 2 IRCCS MultiMedica, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - 2 IRCCS MultiMedica, Italy. AD - 3 Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy. LA - eng PT - Journal Article DEP - 20181213 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 EDAT- 2018/12/14 06:00 MHDA- 2018/12/14 06:00 CRDT- 2018/12/15 06:00 PHST- 2018/12/14 06:00 [pubmed] PHST- 2018/12/14 06:00 [medline] PHST- 2018/12/15 06:00 [entrez] AID - 10.1177/2047487318820976 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2019 Mar;26(5):531-532. doi: 10.1177/2047487318820976. Epub 2018 Dec 13. PMID- 30520012 OWN - NLM STAT- In-Data-Review LR - 20190131 IS - 1532-6535 (Electronic) IS - 0009-9236 (Linking) VI - 105 IP - 2 DP - 2019 Feb TI - Lipid Lowering and Incidence of Cataract, a Role for Fibrates. PG - 318-319 LID - 10.1002/cpt.1269 [doi] FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AUID- ORCID: http://orcid.org/0000-0002-7593-2094 AD - Epidemiology and Preventive Pharmacology Centre, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. AD - IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. LA - eng GR - 2015-0524/Fondazione Cariplo GR - 2015-0564/Fondazione Cariplo GR - PHC-03-2015/667837-2/H2020 REPROGRAM PT - Journal Article DEP - 20181205 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 EDAT- 2018/12/07 06:00 MHDA- 2018/12/07 06:00 CRDT- 2018/12/07 06:00 PHST- 2018/10/12 00:00 [received] PHST- 2018/10/13 00:00 [accepted] PHST- 2018/12/07 06:00 [pubmed] PHST- 2018/12/07 06:00 [medline] PHST- 2018/12/07 06:00 [entrez] AID - 10.1002/cpt.1269 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2019 Feb;105(2):318-319. doi: 10.1002/cpt.1269. Epub 2018 Dec 5. PMID- 30694319 OWN - NLM STAT- MEDLINE DCOM- 20190219 LR - 20190320 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 321 IP - 4 DP - 2019 Jan 29 TI - Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. PG - 364-373 LID - 10.1001/jama.2018.20045 [doi] AB - Importance: Triglycerides and cholesterol are both carried in plasma by apolipoprotein B (ApoB)-containing lipoprotein particles. It is unknown whether lowering plasma triglyceride levels reduces the risk of cardiovascular events to the same extent as lowering low-density lipoprotein cholesterol (LDL-C) levels. Objective: To compare the association of triglyceride-lowering variants in the lipoprotein lipase (LPL) gene and LDL-C-lowering variants in the LDL receptor gene (LDLR) with the risk of cardiovascular disease per unit change in ApoB. Design, Setting, and Participants: Mendelian randomization analyses evaluating the associations of genetic scores composed of triglyceride-lowering variants in the LPL gene and LDL-C-lowering variants in the LDLR gene, respectively, with the risk of cardiovascular events among participants enrolled in 63 cohort or case-control studies conducted in North America or Europe between 1948 and 2017. Exposures: Differences in plasma triglyceride, LDL-C, and ApoB levels associated with the LPL and LDLR genetic scores. Main Outcomes and Measures: Odds ratio (OR) for coronary heart disease (CHD)-defined as coronary death, myocardial infarction, or coronary revascularization-per 10-mg/dL lower concentration of ApoB-containing lipoproteins. Results: A total of 654783 participants, including 91129 cases of CHD, were included (mean age, 62.7 years; 51.4% women). For each 10-mg/dL lower level of ApoB-containing lipoproteins, the LPL score was associated with 69.9-mg/dL (95% CI, 68.1-71.6; P = 7.1 x 10-1363) lower triglyceride levels and 0.7-mg/dL (95% CI, 0.03-1.4; P = .04) higher LDL-C levels; while the LDLR score was associated with 14.2-mg/dL (95% CI, 13.6-14.8; P = 1.4 x 10-465) lower LDL-C and 1.9-mg/dL (95% CI, 0.1-3.9; P = .04) lower triglyceride levels. Despite these differences in associated lipid levels, the LPL and LDLR scores were associated with similar lower risk of CHD per 10-mg/dL lower level of ApoB-containing lipoproteins (OR, 0.771 [95% CI, 0.741-0.802], P = 3.9 x 10-38 and OR, 0.773 [95% CI, 0.747-0.801], P = 1.1 x 10-46, respectively). In multivariable mendelian randomization analyses, the associations between triglyceride and LDL-C levels with the risk of CHD became null after adjusting for differences in ApoB (triglycerides: OR, 1.014 [95% CI, 0.965-1.065], P = .19; LDL-C: OR, 1.010 [95% CI, 0.967-1.055], P = .19; ApoB: OR, 0.761 [95% CI, 0.723-0.798], P = 7.51 x 10-20). Conclusions and Relevance: Triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants were associated with similar lower risk of CHD per unit difference in ApoB. Therefore, the clinical benefit of lowering triglyceride and LDL-C levels may be proportional to the absolute change in ApoB. FAU - Ference, Brian A AU - Ference BA AD - Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, United Kingdom. AD - Institute for Advanced Studies, University of Bristol, Bristol, United Kingdom. AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Kastelein, John J P AU - Kastelein JJP AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Irving Institute for Clinical and Translational Research, Columbia University Vagelos College of Physicians and Surgeons, New York, New York. FAU - Chapman, M John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), Pitie-Salpetriere University Hospital, Paris, France. FAU - Packard, Chris J AU - Packard CJ AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. FAU - Laufs, Ulrich AU - Laufs U AD - Department of Cardiology, University of Leipzig, Leipzig, Germany. FAU - Oliver-Williams, Clare AU - Oliver-Williams C AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Wood, Angela M AU - Wood AM AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Butterworth, Adam S AU - Butterworth AS AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Di Angelantonio, Emanuele AU - Di Angelantonio E AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Danesh, John AU - Danesh J AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Nicholls, Stephen J AU - Nicholls SJ AD - Monash Cardiovascular Research Centre, University, Melbourne, Australia. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Sabatine, Marc S AU - Sabatine MS AD - Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Multimedica IRCCS, Milano, Italy. LA - eng GR - Medical Research Council/United Kingdom GR - European Research Council/International GR - British Heart Foundation/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Apolipoproteins B) RN - 0 (Cholesterol, LDL) RN - 0 (Receptors, LDL) RN - 0 (Triglycerides) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - AIM SB - IM CIN - JAMA. 2019 Jan 29;321(4):347-349. PMID: 30694301 MH - Apolipoproteins B/*blood MH - Case-Control Studies MH - Cholesterol, LDL/*blood MH - Coronary Disease/blood/*genetics MH - Female MH - *Genetic Predisposition to Disease MH - *Genetic Variation MH - Humans MH - Lipoprotein Lipase/*genetics/metabolism MH - Loss of Function Mutation MH - Male MH - Mendelian Randomization Analysis MH - Metabolic Networks and Pathways MH - Middle Aged MH - Prospective Studies MH - Receptors, LDL/*genetics MH - Risk Factors MH - Triglycerides/*blood EDAT- 2019/01/30 06:00 MHDA- 2019/03/21 06:00 CRDT- 2019/01/30 06:00 PHST- 2019/01/30 06:00 [entrez] PHST- 2019/01/30 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] AID - 2722770 [pii] AID - 10.1001/jama.2018.20045 [doi] PST - ppublish SO - JAMA. 2019 Jan 29;321(4):364-373. doi: 10.1001/jama.2018.20045. PMID- 29982592 OWN - NLM STAT- In-Data-Review LR - 20190122 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 40 IP - 4 DP - 2019 Jan 21 TI - PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor. PG - 357-368 LID - 10.1093/eurheartj/ehy357 [doi] AB - Aims: PCSK9 loss of function genetic variants are associated with lower low-density lipoprotein cholesterol but also with higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Here, we investigated the molecular mechanisms underlying this association. Methods and results: Pcsk9 KO, WT, Pcsk9/Ldlr double KO (DKO), Ldlr KO, albumin AlbCre+/Pcsk9LoxP/LoxP (liver-selective Pcsk9 knock-out mice), and AlbCre-/Pcsk9LoxP/LoxP mice were used. GTT, ITT, insulin and C-peptide plasma levels, pancreas morphology, and cholesterol accumulation in pancreatic islets were studied in the different animal models. Glucose clearance was significantly impaired in Pcsk9 KO mice fed with a standard or a high-fat diet for 20 weeks compared with WT animals; insulin sensitivity, however, was not affected. A detailed analysis of pancreas morphology of Pcsk9 KO mice vs. controls revealed larger islets with increased accumulation of cholesteryl esters, paralleled by increased insulin intracellular levels and decreased plasma insulin, and C-peptide levels. This phenotype was completely reverted in Pcsk9/Ldlr DKO mice implying the low-density lipoprotein receptor (LDLR) as the proprotein convertase subtilisin/kexin Type 9 (PCSK9) target responsible for the phenotype observed. Further studies in albumin AlbCre+/Pcsk9LoxP/LoxP mice, which lack detectable circulating PCSK9, also showed a complete recovery of the phenotype, thus indicating that circulating, liver-derived PCSK9, the principal target of monoclonal antibodies, does not impact beta-cell function and insulin secretion. Conclusion: PCSK9 critically controls LDLR expression in pancreas perhaps contributing to the maintenance of a proper physiological balance to limit cholesterol overload in beta cells. This effect is independent of circulating PCSK9 and is probably related to locally produced PCSK9. FAU - Da Dalt, Lorenzo AU - Da Dalt L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Balzarotti, Gloria AU - Balzarotti G AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Dhyani, Ashish AU - Dhyani A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Di Cairano, Eliana AU - Di Cairano E AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. AD - Centro SISA per lo studio dell'Aterosclerosi, Ospedale Bassini, Via Massimo Gorki, 50, Cinisello Balsamo, Italy. FAU - Arnaboldi, Lorenzo AU - Arnaboldi L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - De Metrio, Simona AU - De Metrio S AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Pellegatta, Fabio AU - Pellegatta F AD - Centro SISA per lo studio dell'Aterosclerosi, Ospedale Bassini, Via Massimo Gorki, 50, Cinisello Balsamo, Italy. FAU - Grigore, Liliana AU - Grigore L AD - Centro SISA per lo studio dell'Aterosclerosi, Ospedale Bassini, Via Massimo Gorki, 50, Cinisello Balsamo, Italy. AD - IRCCS Multimedica Hospital, Via Milanese, 300, Sesto San Giovanni, Italy. FAU - Botta, Margherita AU - Botta M AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Uboldi, Patrizia AU - Uboldi P AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Perego, Carla AU - Perego C AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. AD - IRCCS Multimedica Hospital, Via Milanese, 300, Sesto San Giovanni, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via balzaretti,9, Milan, Italy. AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Science, Curtin University, Kent Street, Bentley, Perth 6102, Western Australia, Australia. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 EDAT- 2018/07/10 06:00 MHDA- 2018/07/10 06:00 CRDT- 2018/07/09 06:00 PHST- 2017/09/13 00:00 [received] PHST- 2018/06/04 00:00 [accepted] PHST- 2018/07/10 06:00 [pubmed] PHST- 2018/07/10 06:00 [medline] PHST- 2018/07/09 06:00 [entrez] AID - 5047864 [pii] AID - 10.1093/eurheartj/ehy357 [doi] PST - ppublish SO - Eur Heart J. 2019 Jan 21;40(4):357-368. doi: 10.1093/eurheartj/ehy357. PMID- 30500603 OWN - NLM STAT- In-Data-Review LR - 20190127 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 280 DP - 2019 Jan TI - Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia. PG - 109-117 LID - S0021-9150(18)31472-2 [pii] LID - 10.1016/j.atherosclerosis.2018.11.017 [doi] AB - BACKGROUND AND AIMS: Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased cardiovascular disease risk. Despite multiple LDL-C-lowering therapies, many HeFH patients do not reach LDL-C targets. Mipomersen, an antisense oligonucleotide against apolipoprotein B (apoB), might further lower LDL-C in HeFH patients. We assessed the efficacy and safety of two mipomersen dosing regimens in HeFH patients and explored whether thrice-weekly dosing improves the benefit-risk profile. METHODS: In this double-blind trial, HeFH patients (LDL-C >160mg/dL) on maximal tolerated LDL-lowering therapy were randomized to mipomersen 200mg once weekly (n=104), mipomersen 70mg thrice weekly (n=102), or placebo in matching frequency (n=103) for 60 weeks. Main outcomes were LDL-C, apoB, and lipoprotein(a) levels after 60 weeks of treatment. RESULTS: Mipomersen 200mg once weekly and mipomersen 70mg thrice weekly significantly lowered LDL-C compared with placebo by 21.0% and 18.8%, respectively, and apoB by 22.1% and 21.7% (all p<0.001). Lipoprotein(a) was significantly lowered by 27.7% (p<0.001) with thrice-weekly dosing. Injection-site reactions and flu-like symptoms led to discontinuation in 21.2% (200mg), 17.6% (70mg), and 5.8% (placebo) of participants. Alanine transaminase was elevated (>/=3x upper limit of normal at least once) in 21.2%, 21.6%, and 1.0% of subjects, respectively. CONCLUSIONS: Mipomersen 200mg once weekly and 70mg thrice weekly are effective in lowering apoB-containing lipoproteins in HeFH patients. This is counterbalanced by limited tolerability and increased hepatic transaminase levels in about 21% of patients. The thrice-weekly dosing regimen was associated with lower frequency of flu-like symptoms, which might help avert discontinuation in some patients, but otherwise had no major benefits. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Reeskamp, Laurens F AU - Reeskamp LF AD - Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: l.f.reeskamp@amc.uva.nl. FAU - Kastelein, John J P AU - Kastelein JJP AD - Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. FAU - Moriarty, Patrick M AU - Moriarty PM AD - Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA. FAU - Duell, P Barton AU - Duell PB AD - Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Dipartimento Dieccellenza Scienze Farmacologiche e Biomolecolari, Milano, Italy; IRCCS Multimedica, Milano, Italy. FAU - Santos, Raul D AU - Santos RD AD - Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School, University of Sao Paulo, Sao Paulo, Brazil; Hospital Israelita Albert Einstein, Sao Paulo, Brazil. FAU - Ballantyne, Christie M AU - Ballantyne CM AD - Sections of Cardiology and Cardiovascular Research, Baylor College of Medicine, Houston, TX, USA. LA - eng PT - Journal Article DEP - 20181110 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 OTO - NOTNLM OT - Antisense oligonucleotide OT - Heterozygous familial hypercholesterolemia OT - Lipoproteins OT - Mipomersen OT - Randomized controlled trial OT - apoB EDAT- 2018/12/01 06:00 MHDA- 2018/12/01 06:00 CRDT- 2018/12/01 06:00 PHST- 2018/09/20 00:00 [received] PHST- 2018/10/22 00:00 [revised] PHST- 2018/11/08 00:00 [accepted] PHST- 2018/12/01 06:00 [pubmed] PHST- 2018/12/01 06:00 [medline] PHST- 2018/12/01 06:00 [entrez] AID - S0021-9150(18)31472-2 [pii] AID - 10.1016/j.atherosclerosis.2018.11.017 [doi] PST - ppublish SO - Atherosclerosis. 2019 Jan;280:109-117. doi: 10.1016/j.atherosclerosis.2018.11.017. Epub 2018 Nov 10. PMID- 30340914 OWN - NLM STAT- In-Data-Review LR - 20181121 IS - 1879-260X (Electronic) IS - 0925-4439 (Linking) VI - 1865 IP - 1 DP - 2019 Jan TI - Corrigendum to "Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation" [Biochim. Biophys. Acta, 1862 (2016) 1182-1190]. PG - 262 LID - S0925-4439(18)30352-1 [pii] LID - 10.1016/j.bbadis.2018.09.017 [doi] FAU - Bonacina, F AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Barbieri, S S AU - Barbieri SS AD - IRCCS, Centro Cardiologico Monzino, Milan, Italy. FAU - Cutuli, L AU - Cutuli L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Amadi, P AU - Amadi P AD - IRCCS, Centro Cardiologico Monzino, Milan, Italy. FAU - Don, A AU - Don A AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Sironi, M AU - Sironi M AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Tartari, S AU - Tartari S AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Mantovani, A AU - Mantovani A AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Bottazzi, B AU - Bottazzi B AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Garlanda, C AU - Garlanda C AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Tremoli, E AU - Tremoli E AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS, Centro Cardiologico Monzino, Milan, Italy. FAU - Catapano, A L AU - Catapano AL AD - IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Milan, Italy; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: danilo.norata@unimi.it. LA - eng PT - Published Erratum DEP - 20181016 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 EFR - Biochem Biophys Res Commun. 2018 Sep 26;504(1):270-276. PMID: 30172372 EDAT- 2018/10/21 06:00 MHDA- 2018/10/21 06:00 CRDT- 2018/10/21 06:00 PHST- 2018/10/21 06:00 [pubmed] PHST- 2018/10/21 06:00 [medline] PHST- 2018/10/21 06:00 [entrez] AID - S0925-4439(18)30352-1 [pii] AID - 10.1016/j.bbadis.2018.09.017 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2019 Jan;1865(1):262. doi: 10.1016/j.bbadis.2018.09.017. Epub 2018 Oct 16. PMID- 30295742 OWN - NLM STAT- In-Data-Review LR - 20181221 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 115 IP - 1 DP - 2019 Jan 1 TI - High-density lipoprotein cholesterol levels, cardiovascular disease risk, and cancer: a relation which does not apply to all? PG - 6-7 LID - 10.1093/cvr/cvy247 [doi] FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti, 9 - Milan, Italy. AD - IRCCS MultiMedica, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - IRCCS MultiMedica, Milan, Italy. AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti, 9 - Milan, Italy. AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 EDAT- 2018/10/09 06:00 MHDA- 2018/10/09 06:00 CRDT- 2018/10/09 06:00 PHST- 2018/10/09 06:00 [pubmed] PHST- 2018/10/09 06:00 [medline] PHST- 2018/10/09 06:00 [entrez] AID - 5115992 [pii] AID - 10.1093/cvr/cvy247 [doi] PST - ppublish SO - Cardiovasc Res. 2019 Jan 1;115(1):6-7. doi: 10.1093/cvr/cvy247. PMID- 30522632 OWN - NLM STAT- In-Data-Review LR - 20181207 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 72 IP - 23 Pt B DP - 2018 Dec 11 TI - Reprint of: Impact of Lipids on Cardiovascular Health: JACC Health Promotion Series. PG - 2980-2995 LID - S0735-1097(18)38853-3 [pii] LID - 10.1016/j.jacc.2018.10.021 [doi] AB - People who maintain ideal cardiovascular heath have a low lifetime risk of cardiovascular disease. Therefore, encouraging people to achieve ideal cardiovascular health represents an important opportunity to improve the prevention of cardiovascular disease. However, preventing cardiovascular disease by promoting ideal cardiovascular health requires shifting the focus from treating disease after it develops to preventing cardiovascular events before they happen by slowing the progression of atherosclerosis. Because atherogenic lipoproteins play a central causal role in the initiation and progression of atherosclerosis, maintaining optimal lipid levels is necessary to achieve ideal cardiovascular health. This review describes the cumulative effect of lipid-carrying lipoproteins on the risk of cardiovascular disease, estimates the magnitude of the clinical benefit that can be achieved by maintaining optimal lipid levels, identifies the most effective timing for implementing strategies designed to achieve optimal lipid levels, and provides a clinical pathway to help people achieve the lipid levels necessary for ideal cardiovascular health. CI - Copyright (c) 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Ference, Brian A AU - Ference BA AD - Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, United Kingdom. FAU - Graham, Ian AU - Graham I AD - School of Medicine, Trinity College, Dublin, Ireland. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Department of Cardiology, Hacettepe University, Ankara, Turkey. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 OTO - NOTNLM OT - apolipoproteins OT - cholesterol OT - low-density lipoproteins OT - population OT - risk OT - total burden EDAT- 2018/12/14 06:00 MHDA- 2018/12/14 06:00 CRDT- 2018/12/08 06:00 PHST- 2018/02/19 00:00 [received] PHST- 2018/06/03 00:00 [revised] PHST- 2018/06/26 00:00 [accepted] PHST- 2018/12/08 06:00 [entrez] PHST- 2018/12/14 06:00 [pubmed] PHST- 2018/12/14 06:00 [medline] AID - S0735-1097(18)38853-3 [pii] AID - 10.1016/j.jacc.2018.10.021 [doi] PST - ppublish SO - J Am Coll Cardiol. 2018 Dec 11;72(23 Pt B):2980-2995. doi: 10.1016/j.jacc.2018.10.021. PMID- 30165636 OWN - NLM STAT- In-Data-Review LR - 20190125 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 40 DP - 2018 Oct 21 TI - Associations between very low concentrations of low density lipoprotein cholesterol, high sensitivity C-reactive protein, and health outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study. PG - 3641-3653 LID - 10.1093/eurheartj/ehy533 [doi] AB - Aims: Recent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hs-CRP), and clinical outcomes in a free-living US population. Methods and results: We used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at 'high risk' for coronary events with a Framingham Coronary Risk Score of >/=10% or atherosclerotic cardiovascular disease (ASCVD) risk >/=7.5% in order to explore relationships between low LDL-C [<70 mg/dL (1.8 mmol/L) in comparison to >/=70 mg/dL (1.8 mmol/L)]; hs-CRP <2 compared with >/=2 mg/L and clinical outcomes [all-cause mortality, incident coronary heart disease (CHD), and incident stroke]. To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE). In this analysis, 6136 REGARDS high-risk participants were included. In the MICE analysis, participants with high LDL-C (>/=70 mg/dL) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke [hazard ratio (HR) 0.69, 0.47-0.997], incident CHD (HR 0.71, 0.53-0.95), and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs-CRP (>/=2 mg/L). In participants with high hs-CRP (>/=2 mg/dL), low LDL-C [<70 mg/dL (1.8 mmol/L)] was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74). Conclusions: In this high-risk population, we found that low hs-CRP (<2 mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD, and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD. FAU - Penson, Peter E AU - Penson PE AD - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, UK. FAU - Long, D Leann AU - Long DL AD - Department of Biostatistics, University of Alabama at Birmingham School of Public Health, 1665 University Boulevard, Birmingham, AL, USA. FAU - Howard, George AU - Howard G AD - Department of Biostatistics, University of Alabama at Birmingham School of Public Health, 1665 University Boulevard, Birmingham, AL, USA. FAU - Toth, Peter P AU - Toth PP AD - The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, MD, USA. AD - Preventive Cardiology, CGH Medical Center, 01 East Miller Road, Sterling, IL, USA. FAU - Muntner, Paul AU - Muntner P AD - Department of Epidemiology, University of Alabama at Birmingham, 700 University Boulevard, Suite LHL 450, Birmingham, AL, USA. FAU - Howard, Virginia J AU - Howard VJ AD - Department of Epidemiology, University of Alabama at Birmingham, 700 University Boulevard, Suite LHL 450, Birmingham, AL, USA. FAU - Safford, Monica M AU - Safford MM AD - Department of Medicine, Weill Cornell Medicine, 1320 York Avenue, HT-621 New York, NY, USA. FAU - Jones, Steven R AU - Jones SR AD - The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, MD, USA. FAU - Martin, Seth S AU - Martin SS AD - The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 600 N. Wolfe St, Carnegie 565-G, Baltimore, MD, USA. FAU - Mazidi, Mohsen AU - Mazidi M AD - Department of Biology and Biological Engineering, Food and Nutrition Science, Chalmers University of Technology, Kemigarden 4, SE-412 96 Gothenburg, Sweden. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti 9, Milan, Italy. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Zeromskiego 113, Lodz, Poland. AD - Polish Mother's Memorial Hospital Research Institute, Rzgowska 281/288; Lodz, Poland. AD - Cardiovascular Research Centre, University of Zielona Gora, Zyty 28; Zielona Gora, Poland. LA - eng GR - R01 HL080477/HL/NHLBI NIH HHS/United States PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 PMC - PMC6195947 EDAT- 2018/08/31 06:00 MHDA- 2018/08/31 06:00 CRDT- 2018/08/31 06:00 PMCR- 2019/10/21 00:00 PHST- 2018/07/12 00:00 [received] PHST- 2018/08/09 00:00 [accepted] PHST- 2019/10/21 00:00 [pmc-release] PHST- 2018/08/31 06:00 [pubmed] PHST- 2018/08/31 06:00 [medline] PHST- 2018/08/31 06:00 [entrez] AID - 5077833 [pii] AID - 10.1093/eurheartj/ehy533 [doi] PST - ppublish SO - Eur Heart J. 2018 Oct 21;39(40):3641-3653. doi: 10.1093/eurheartj/ehy533. PMID- 29069365 OWN - NLM STAT- In-Data-Review LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 38 DP - 2018 Oct 7 TI - Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases. PG - 3521-3527 LID - 10.1093/eurheartj/ehx581 [doi] AB - A large number of cardiovascular events are not prevented by current therapeutic regimens. In search for additional, innovative strategies, immune cells have been recognized as key players contributing to atherosclerotic plaque progression and destabilization. Particularly the role of innate immune cells is of major interest, following the recent paradigm shift that innate immunity, long considered to be incapable of learning, does exhibit immunological memory mediated via epigenetic reprogramming. Compelling evidence shows that atherosclerotic risk factors promote immune cell migration by pre-activation of circulating innate immune cells. Innate immune cell activation via metabolic and epigenetic reprogramming perpetuates a systemic low-grade inflammatory state in cardiovascular disease (CVD) that is also common in other chronic inflammatory disorders. This opens a new therapeutic area in which metabolic or epigenetic modulation of innate immune cells may result in decreased systemic chronic inflammation, alleviating CVD, and its co-morbidities. FAU - Hoogeveen, Renate M AU - Hoogeveen RM AD - Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands. FAU - Nahrendorf, Matthias AU - Nahrendorf M AD - Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, 55 Fruit Street Boston, MA, USA. FAU - Riksen, Niels P AU - Riksen NP AD - Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, Nijmegen, The Netherlands. FAU - Netea, Mihai G AU - Netea MG AD - Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, Nijmegen, The Netherlands. FAU - de Winther, Menno P J AU - de Winther MPJ AD - Department of Medical Biochemistry, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands. FAU - Lutgens, Esther AU - Lutgens E AD - Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University (LMU), Pettenkoferstrasse 9, Munich, Germany. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - The Copenhagen General Population Study and Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Ringvej 75, Herlev, Copenhagen, Denmark. FAU - Neidhart, Michel AU - Neidhart M AD - Center of Experimental Rheumatology, University Hospital Zurich, Schlieren, Switzerland. FAU - Stroes, Erik S G AU - Stroes ESG AD - Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti, Milano, Italy. FAU - Bekkering, Siroon AU - Bekkering S AD - Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands. AD - Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, Nijmegen, The Netherlands. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 PMC - PMC6174026 EDAT- 2017/10/27 06:00 MHDA- 2017/10/27 06:00 CRDT- 2017/10/26 06:00 PHST- 2017/06/28 00:00 [received] PHST- 2017/10/12 00:00 [accepted] PHST- 2017/10/27 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] PHST- 2017/10/26 06:00 [entrez] AID - 4563761 [pii] AID - 10.1093/eurheartj/ehx581 [doi] PST - ppublish SO - Eur Heart J. 2018 Oct 7;39(38):3521-3527. doi: 10.1093/eurheartj/ehx581. PMID- 30270089 OWN - NLM STAT- In-Data-Review LR - 20181001 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 277 DP - 2018 Oct TI - Familial hypercholesterolemia treatments: Guidelines and new therapies. PG - 483-492 LID - S0021-9150(18)31171-7 [pii] LID - 10.1016/j.atherosclerosis.2018.06.859 [doi] AB - Familial hypercholesterolemia (FH) is a genetic disorder resulting from mutations in genes encoding proteins involved in the metabolism of low density lipoproteins (LDL) and characterized by premature cardiovascular disease due to the exposure to high levels of LDL-cholesterol (LDL-C) from birth. Thus, the early identification of FH subjects, followed by appropriate treatment is essential to prevent or at least delay the onset of cardiovascular events. However, FH is largely underdiagnosed; in addition, FH patients are frequently not adequately treated, despite the availability of several pharmacological therapies to significantly reduce LDL-C levels. Current guidelines recommend LDL-C targets for FH (either heterozygotes [HeFH] or homozygotes [HoFH]) <100mg/dL (<2.6mmol/L) for adults or <70mg/dL (<1.8mmol/L) for adults with CHD or diabetes, and <135mg/dL (<3.5mmol/L) for children. With the pharmacological options now available, which include statins as a first approach, ezetimibe, and the recently approved monoclonal antibodies targeting PCSK9, the guideline recommended LDL-C target levels can be achieved in the majority of heterozygous FH subjects, while for the most severe forms of homozygous FH, the addition of therapies such as lomitapide either with or without apheresis may be required. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Raal, Frederick J AU - Raal FJ AD - Carbohydrate & Lipid Metabolism Research Unit, Division of Endocrinology & Metabolism, Department of Medicine, Faculty of Health Sciences, Johannesburg Hospital, University of the Witwatersrand, Parktown, Johannesburg, South Africa. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 OTO - NOTNLM OT - Familial hypercholesterolemia OT - Guidelines OT - Lipid-lowering drugs OT - Low density lipoprotein receptor EDAT- 2018/10/03 06:00 MHDA- 2018/10/03 06:00 CRDT- 2018/10/02 06:00 PHST- 2018/04/18 00:00 [received] PHST- 2018/05/28 00:00 [revised] PHST- 2018/06/14 00:00 [accepted] PHST- 2018/10/02 06:00 [entrez] PHST- 2018/10/03 06:00 [pubmed] PHST- 2018/10/03 06:00 [medline] AID - S0021-9150(18)31171-7 [pii] AID - 10.1016/j.atherosclerosis.2018.06.859 [doi] PST - ppublish SO - Atherosclerosis. 2018 Oct;277:483-492. doi: 10.1016/j.atherosclerosis.2018.06.859. PMID- 30270079 OWN - NLM STAT- In-Data-Review LR - 20181109 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 277 DP - 2018 Oct TI - Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study. PG - 413-418 LID - S0021-9150(18)31307-8 [pii] LID - 10.1016/j.atherosclerosis.2018.08.013 [doi] AB - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. METHODS: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. RESULTS: The DLCN score was applied on a sample of 1377 adults (mean age 42.9+/-14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. CONCLUSIONS: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Olmastroni, Elena AU - Olmastroni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. Electronic address: alberico.catapano@unimi.it. CN - MEMBERS OF THE LIPIGEN STEERING COMMETTEE CN - PRINCIPAL INVESTIGATORS: Coordinator center CN - Participant Centers CN - Participant Laboratories CN - COLLABORATORS CN - STUDY CENTRAL LABORATORY AND ANALYSIS GROUP LA - eng PT - Journal Article PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 OTO - NOTNLM OT - Dutch Lipid Clinic Network score OT - Familial hypercholesterolemia OT - Genetic testing IR - Arca M FIR - Arca, Marcello IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Averna M FIR - Averna, Maurizio IRAD- Dipartimento Biomedico di Medicina Interna e Specialistica, Universita di Palermo, Palermo, Italy. IR - Bertolini S FIR - Bertolini, Stefano IRAD- Centro Ambulatorio Dislipidemie, U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Calandra S FIR - Calandra, Sebastiano IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Catapano AL FIR - Catapano, Alberico Luigi IRAD- Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita Degli Studi di Milano, IRCCS Multimedica, Milan, Italy. IR - Tarugi P FIR - Tarugi, Patrizia IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Pellegatta F FIR - Pellegatta, Fabio IRAD- Centro per Lo Studio Dell'Aterosclerosi, IRCCS Multimedica, Sesto San Giovanni, Italy. IR - Angelico F FIR - Angelico, Francesco IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Arca M FIR - Arca, Marcello IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Averna M FIR - Averna, Maurizio IRAD- Dipartimento Biomedico di Medicina Interna e Specialistica, Universita di Palermo, Palermo, Italy. IR - Bartuli A FIR - Bartuli, Andrea IRAD- Ambulatorio Polispecialistico per le Malattie Rare, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy. IR - Biasucci G FIR - Biasucci, Giacomo IRAD- Centro Dislipidemie in Eta Evolutiva U.O. Pediatria e Neonatologia, Ospedale G. da Saliceto, Piacenza, Italy. IR - Biolo G FIR - Biolo, Gianni IRAD- S.S. Diabetologia e Malattie Metaboliche, U.C.O. Clinica Medica Generale, Azienda Ospedaliera Universitaria OORR, Ospedale Maggiore, Trieste, Italy. IR - Bonanni L FIR - Bonanni, Luca IRAD- Ambulatorio Dislipidemie, UO Medicina Interna, Ospedale Dell'Angelo di Mestre, Venice, Italy. IR - Bonomo K FIR - Bonomo, Katia IRAD- AOU San Luigi Gonzaga, Orbassano, Turin, Italy. IR - Borghi C FIR - Borghi, Claudio IRAD- U.O. di Medicina Interna, Centro Aterosclerosi, Ambulatorio Dislipidemie, Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. IR - Bossi AC FIR - Bossi, Antonio Carlo IRAD- U.O.C. Malattie Endocrine e Centro Regionale per Il Diabete (Diabetologia), Ospedale "Treviglio-Caravaggio" di Treviglio, Bergamo, Italy. IR - Branchi A FIR - Branchi, Adriana IRAD- Ambulatorio Dislipidemie, Centro per Lo Studio e La Prevenzione Dell'Arteriosclerosi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico e Dipartimento di Scienze Cliniche e di Comunita, Universita Degli Studi di Milano, Milan, Italy. IR - Carubbi F FIR - Carubbi, Francesca IRAD- U.O. Medicina Ad Indirizzo Metabolico-nutrizionistico, Centro Dislipidemie e Centro di Riferimento Regionale per le Malattie Metaboliche Rare, Nuovo Ospedale S. Agostino Estense (NOCSAE), Modena, Italy. IR - Cipollone F FIR - Cipollone, Francesco IRAD- Centro di Alta Specializzazione per La Prevenzione Dell'arteriosclerosi, Centro di Eccellenza ESH per L'ipertensione Arteriosa, Centro di Riferimento Regionale per le Dislipemie, Ospedale Policlino S.S. Annunziata, Chieti, Italy. IR - Citroni N FIR - Citroni, Nadia IRAD- Centro Dislipidemia, UO Medicina Interna, Ospedale Santa Chiara, Trento, Italy. IR - Federici M FIR - Federici, Massimo IRAD- Dipartimento Medicina Interna, Centro per L'Aterosclerosi, Policlinico Universtario "Tor Vergata", Rome, Italy. IR - Ferri C FIR - Ferri, Claudio IRAD- Centro Ipertensione Arteriosa e Prevenzione Cardiovascolare UOC Medicina Interna e Nefrologia, L'Aquila, Italy. IR - Fiorenza AM FIR - Fiorenza, Anna Maria IRAD- Dip. Medicina Interna, Centro Prevenzione e Cura Dell'aterosclerosi, A.O. "Guido Salvini", Garbagnate Milanese, Milan, Italy. IR - Giaccari A FIR - Giaccari, Andrea IRAD- UOC Endocrinologia e Malattie Del Metabolismo, Policlinico Gemelli, Rome, Italy. IR - Giorgino F FIR - Giorgino, Francesco IRAD- U.O. Endocrinologia, Ambulatori di Diabetologia e Malattie Metaboliche, A.O. Universitaria Policlinico Consorziale, Universita Degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Guardamagna O FIR - Guardamagna, Ornella IRAD- U.O. Dislipidemie e Prevenzione Cardiovascolare, Ospedale Regina Margherita, Turin, Italy. IR - Iannuzzi A FIR - Iannuzzi, Arcangelo IRAD- U.O. Medicina Interna 5, Centro per le Malattie da Arteriosclerosi, AORN Cardarelli, Naples, Italy. IR - Iughetti L FIR - Iughetti, Lorenzo IRAD- U.O. Clinica Pediatrica, Policlinico di Modena, Modena, Italy. IR - Lupattelli G FIR - Lupattelli, Graziana IRAD- U.O. Medicina Interna Angiologia, Malattie da Arteriosclerosi, Ambulatorio di Malattie Del Ricambio Lipidico, Ospedale Santa Maria Della Misericordia, Perugia, Italy. IR - Lupi A FIR - Lupi, Alessandro IRAD- ASL VCO, UO SOC Cardiologia, Ospedale Castelli, Verbania, Italy. IR - Mandraffino G FIR - Mandraffino, Giuseppe IRAD- Dipartimento di Medicina Interna e Terapia Medica, Centro per La Diagnosi e Cura Della Dislipidemia e Prevenzione Dell'Aterosclerosi, A.O. Universitaria Policlinico "G.Martino", Messina, Italy. IR - Marcucci R FIR - Marcucci, Rossella IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Maroni L FIR - Maroni, Lorenzo IRAD- Ambulatorio Ipertensione Dislipidemie, U.O. Medicina Generale, ASST Valle Olona, Ospedale di Gallarate, Gallarate, Italy. IR - Miccoli R FIR - Miccoli, Roberto IRAD- U.O. Diabetologia e Malattie Metaboliche, Centro per La Prevenzione e La Terapia Delle Dislipidemie e Dell'aterosclerosi, A.O.U. Pisana Ospedale Cisanello, Pisa, Italy. IR - Mombelli G FIR - Mombelli, Giuliana IRAD- Centro Universitario Dislipidemie "E. Grossi Paoletti", A.O. Ospedale Niguarda Ca' Granda, Milan, Italy. IR - Muntoni S FIR - Muntoni, Sandro IRAD- Centro per le Malattie Dismetaboliche e L'arteriosclerosi, Associazione ME.DI.CO Onlus, Cagliari, Italy. IR - Pecchioli V FIR - Pecchioli, Valerio IRAD- UOSD 'Prevenzione Cardiovascolare', Dipartimento di Scienze Mediche, Azienda Sanitaria Locale Frosinone, Frosinone, Italy. IR - Pederiva C FIR - Pederiva, Cristina IRAD- U.O. Clinica Pediatrica, Servizio Clinico Dislipidemie per Lo Studio e La Prevenzione Dell'Aterosclerosi in Eta Pediatrica, Ospedale San Paolo, Milan, Italy. IR - Pipolo A FIR - Pipolo, Antonio IRAD- AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy. IR - Pisciotta L FIR - Pisciotta, Livia IRAD- U.O. Clinica di Medicina Interna 1, Ambulatorio Dislipidemie, IRCCS, A.O.U. San Martino, IST, Genoa, Italy. IR - Pujia A FIR - Pujia, Arturo IRAD- A.O.U. Mater Domini, Catanzaro, UOC di Nutrizione Clinica, Ambulatorio Dislipidemie, Catanzaro, Italy. IR - Purrello F FIR - Purrello, Francesco IRAD- U.O. Medicina Interna, Ospedale "Garibaldi Nesima", Catania, Italy. IR - Repetti E FIR - Repetti, Elena IRAD- Societa di Diabetologia e Malattie Metaboliche, Asti, Italy. IR - Rubba P FIR - Rubba, Paolo IRAD- Centro Coordinamento Regionale per le Iperlipidemie, AOU Policlinico Federico II, Naples, Italy. IR - Sabba C FIR - Sabba, Carlo IRAD- U.O. di Medicina Interna "Frugoni" e Centro di Assistenza e Ricerca Malattie Rare, A.O. Universitaria Policlinico Consorziale, Universita Degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Sampietro T FIR - Sampietro, Tiziana IRAD- U.O. Lipoaferesi, Centro Regionale di Riferimento per La Diagnosi e Cura Delle Dislipidemie Ereditarie, Fondazione Toscana "G. Monasterio", Pisa, Italy. IR - Sarzani R FIR - Sarzani, Riccardo IRAD- Clinica di Medicina Interna e Geriatria, Centro di Riferimento Regionale Ipertensione Arteriosa e Malattie Cardiovascolari, INRCA Ospedale "Sestilli" e Azienda Ospedaliero-Universitaria Ospedali Riuniti di Torrette di Ancona, Ancona, Italy. IR - Tagliabue MP FIR - Tagliabue, Milena Paola IRAD- SCDU Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Universita di Torino, Turin, Italy. IR - Trenti C FIR - Trenti, Chiara IRAD- Arcispedale S. Maria Nuova, Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy. IR - Vigna GB FIR - Vigna, Giovanni Battista IRAD- U.O Medicina Interna Universitaria, Centro per Lo Studio Delle Dislipidemie e Dell'Aterosclerosi Azienda Ospedaliero-Universitaria di Ferrara, Polo di Cona, Ferrara, Italy. IR - Werba JP FIR - Werba, Jose Pablo IRAD- U.O. Ambulatorio Prevenzione Aterosclerosi IRCCS Cardiologico Monzino, Milan, Italy. IR - Zambon S FIR - Zambon, Sabina IRAD- U.O. Clinica Medica 1, Centro Dislipidemie e Aterosclerosi, A.O. di Padova, Padua, Italy. IR - Zenti MG FIR - Zenti, Maria Grazia IRAD- U.O. Endocrinologia, Diabetologia e Malattie Del Metabolismo, Centro Regionale Specializzato per La Diagnosi e Terapia Delle Dislipidemie e Aferesi Terapeutica, A.O. Universitaria Integrata di Verona, Verona, Italy. IR - Minicocci I FIR - Minicocci, Ilenia IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Noto D FIR - Noto, Davide IRAD- Dipartimento Biomedico di Medicina Interna e Specialistica, Universita di Palermo, Palermo, Italy. IR - Bertolini S FIR - Bertolini, Stefano IRAD- Centro Ambulatorio Dislipidemie, U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Calandra S FIR - Calandra, Sebastiano IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Fortunato G FIR - Fortunato, Giuliana IRAD- Laboratorio di Screening di Malattie Metaboliche, CEINGE - Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche, Azienda Ospedaliera Universitaria "Federico II", Naples, Italy. IR - Banderali G FIR - Banderali, Giuseppe IRAD- U.O. Clinica Pediatrica, Servizio Clinico Dislipidemie per Lo Studio e La Prevenzione Dell'Aterosclerosi in Eta Pediatrica, Ospedale San Paolo, Milan, Italy. IR - Benso A FIR - Benso, Andrea IRAD- SCDU Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Universita di Torino, Turin, Italy. IR - Bigolin P FIR - Bigolin, Paola IRAD- U.O. Clinica Medica 1, Centro Dislipidemie e Aterosclerosi, A.O. di Padova, Padua, Italy. IR - Bonora E FIR - Bonora, Enzo IRAD- U.O. Endocrinologia, Diabetologia e Malattie Del Metabolismo, Centro Regionale Specializzato per La Diagnosi e Terapia Delle Dislipidemie e Aferesi Terapeutica, A.O. Universitaria Integrata di Verona, Verona, Italy. IR - Bruzzi P FIR - Bruzzi, Patrizia IRAD- U.O. Clinica Pediatrica, Policlinico di Modena, Modena, Italy. IR - Bucci M FIR - Bucci, Marco IRAD- Centro di Alta Specializzazione per La Prevenzione Dell'arteriosclerosi, Centro di Eccellenza ESH per L'ipertensione Arteriosa, Centro di Riferimento Regionale per le Dislipemie, Ospedale Policlino S.S. Annunziata, Chieti, Italy. IR - Buonuomo PS FIR - Buonuomo, Paola Sabrina IRAD- Ambulatorio Polispecialistico per le Malattie Rare, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy. IR - Capra ME FIR - Capra, Maria Elena IRAD- Centro Dislipidemie in Eta Evolutiva U.O. Pediatria e Neonatologia, Ospedale G. da Saliceto, Piacenza, Italy. IR - Cardolini I FIR - Cardolini, Iris IRAD- Dipartimento Medicina Interna, Centro per L'Aterosclerosi, Policlinico Universtario "Tor Vergata", Rome, Italy. IR - Cefalu B FIR - Cefalu, Baldassarre IRAD- Dipartimento Biomedico di Medicina Interna e Specialistica, Universita di Palermo, Palermo, Italy. IR - Cervelli N FIR - Cervelli, Nazzareno IRAD- Centro Ipertensione Arteriosa e Prevenzione Cardiovascolare UOC Medicina Interna e Nefrologia, L'Aquila, Italy. IR - Chiariello G FIR - Chiariello, Giuseppe IRAD- U.O. Medicina Interna 5, Centro per le Malattie da Arteriosclerosi, AORN Cardarelli, Naples, Italy. IR - Cocci G FIR - Cocci, Guido IRAD- Clinica di Medicina Interna e Geriatria, Centro di Riferimento Regionale Ipertensione Arteriosa e Malattie Cardiovascolari, INRCA Ospedale "Sestilli" e Azienda Ospedaliero-Universitaria Ospedali Riuniti di Torrette di Ancona, Ancona, Italy. IR - Colombo E FIR - Colombo, Emanuela IRAD- Dip. Medicina Interna, Centro Prevenzione e Cura Dell'aterosclerosi, A.O. "Guido Salvini", Garbagnate Milanese, Milan, Italy. IR - Cremonini AL FIR - Cremonini, Anna Laura IRAD- U.O. Clinica di Medicina Interna 1, Ambulatorio Dislipidemie, IRCCS, A.O.U. San Martino, IST, Genoa, Italy. IR - D'Addato S FIR - D'Addato, Sergio IRAD- U.O. di Medicina Interna, Centro Aterosclerosi, Ambulatorio Dislipidemie, Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. IR - D'Erasmo L FIR - D'Erasmo, Laura IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Dal Pino B FIR - Dal Pino, Beatrice IRAD- U.O. Lipoaferesi, Centro Regionale di Riferimento per La Diagnosi e Cura Delle Dislipidemie Ereditarie, Fondazione Toscana "G. Monasterio", Pisa, Italy. IR - De Sanctis L FIR - De Sanctis, Luisa IRAD- U.O. Dislipidemie e Prevenzione Cardiovascolare, Ospedale Regina Margherita, Turin, Italy. IR - De Vita E FIR - De Vita, Emanuele IRAD- AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy. IR - Del Ben M FIR - Del Ben, Maria IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Di Costanzo A FIR - Di Costanzo, Alessia IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Di Taranto MD FIR - Di Taranto, Maria Donata IRAD- Laboratorio di Screening di Malattie Metaboliche, CEINGE - Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche, Azienda Ospedaliera Universitaria "Federico II", Naples, Italy. IR - Fasano T FIR - Fasano, Tommaso IRAD- Arcispedale S. Maria Nuova, Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy. IR - Gentile L FIR - Gentile, Luigi IRAD- Societa di Diabetologia e Malattie Metaboliche, Asti, Italy. IR - Gentile M FIR - Gentile, Marco IRAD- Centro Coordinamento Regionale per le Iperlipidemie, AOU Policlinico Federico II, Naples, Italy. IR - Ghirardello O FIR - Ghirardello, Omar IRAD- U.O Medicina Interna Universitaria, Centro per Lo Studio Delle Dislipidemie e Dell'Aterosclerosi Azienda Ospedaliero-Universitaria di Ferrara, Polo di Cona, Ferrara, Italy. IR - Grigore L FIR - Grigore, Liliana IRAD- Centro per Lo Studio Dell'Aterosclerosi, IRCCS Multimedica, Sesto San Giovanni, Italy. IR - Lussu M FIR - Lussu, Milena IRAD- Centro per le Malattie Dismetaboliche e L'arteriosclerosi, Associazione ME.DI.CO Onlus, Cagliari, Italy. IR - Meregalli G FIR - Meregalli, Giancarla IRAD- U.O.C. Malattie Endocrine e Centro Regionale per Il Diabete (Diabetologia), Ospedale "Treviglio-Caravaggio" di Treviglio, Bergamo, Italy. IR - Moffa S FIR - Moffa, Simona IRAD- UOC Endocrinologia e Malattie Del Metabolismo, Policlinico Gemelli, Rome, Italy. IR - Montalcini T FIR - Montalcini, Tiziana IRAD- A.O.U. Mater Domini, Catanzaro, UOC di Nutrizione Clinica, Ambulatorio Dislipidemie, Catanzaro, Italy. IR - Morgia V FIR - Morgia, Valeria IRAD- UOSD 'Prevenzione Cardiovascolare', Dipartimento di Scienze Mediche, Azienda Sanitaria Locale Frosinone, Frosinone, Italy. IR - Nascimbeni F FIR - Nascimbeni, Fabio IRAD- U.O. Medicina Ad Indirizzo Metabolico-nutrizionistico, Centro Dislipidemie e Centro di Riferimento Regionale per le Malattie Metaboliche Rare, Nuovo Ospedale S. Agostino Estense (NOCSAE), Modena, Italy. IR - Pasta A FIR - Pasta, Andrea IRAD- Centro Ambulatorio Dislipidemie, U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Pavanello C FIR - Pavanello, Chiara IRAD- Centro Universitario Dislipidemie "E. Grossi Paoletti", A.O. Ospedale Niguarda Ca' Granda, Milan, Italy. IR - Saitta A FIR - Saitta, Antonino IRAD- Dipartimento di Medicina Interna e Terapia Medica, Centro per La Diagnosi e Cura Della Dislipidemia e Prevenzione Dell'Aterosclerosi, A.O. Universitaria Policlinico "G.Martino", Messina, Italy. IR - Scicali R FIR - Scicali, Roberto IRAD- U.O. Medicina Interna, Ospedale "Garibaldi Nesima", Catania, Italy. IR - Siepi D FIR - Siepi, Donatella IRAD- U.O. Medicina Interna Angiologia, Malattie da Arteriosclerosi, Ambulatorio di Malattie Del Ricambio Lipidico, Ospedale Santa Maria Della Misericordia, Perugia, Italy. IR - Spagnolli W FIR - Spagnolli, Walter IRAD- Centro Dislipidemia, UO Medicina Interna, Ospedale Santa Chiara, Trento, Italy. IR - Spina R FIR - Spina, Rossella IRAD- Dipartimento Biomedico di Medicina Interna e Specialistica, Universita di Palermo, Palermo, Italy. IR - Sticchi E FIR - Sticchi, Elena IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Suppressa P FIR - Suppressa, Patrizia IRAD- U.O. di Medicina Interna "Frugoni" e Centro di Assistenza e Ricerca Malattie Rare, A.O. Universitaria Policlinico Consorziale, Universita Degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Tarugi P FIR - Tarugi, Patrizia IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Vigo L FIR - Vigo, Lorenzo IRAD- U.O. Ambulatorio Prevenzione Aterosclerosi IRCCS Cardiologico Monzino, Milan, Italy. IR - Vinci P FIR - Vinci, Pierandrea IRAD- S.S. Diabetologia e Malattie Metaboliche, U.C.O. Clinica Medica Generale, Azienda Ospedaliera Universitaria OORR, Ospedale Maggiore, Trieste, Italy. IR - Catapano AL FIR - Catapano, Alberico Luigi IRAD- Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita Degli Studi di Milano, IRCCS Multimedica, Milan, Italy. IR - Casula M FIR - Casula, Manuela IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita Degli Studi di Milano, Milan, Italy. IR - Manzato E FIR - Manzato, Enzo IRAD- Dipartimento di Medicina (DIMED), Sezione Geriatrica, Universita di Padova, Padua, Italy. IR - Olmastroni E FIR - Olmastroni, Elena IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita Degli Studi di Milano, Milan, Italy. IR - Tragni E FIR - Tragni, Elena IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita Degli Studi di Milano, Milan, Italy. IR - Zampoleri V FIR - Zampoleri, Veronica IRAD- Centro per Lo Studio Dell'Aterosclerosi, Ospedale E. Bassini, Cinisello Balsamo, Milan, Italy. EDAT- 2018/10/03 06:00 MHDA- 2018/10/03 06:00 CRDT- 2018/10/02 06:00 PHST- 2018/04/17 00:00 [received] PHST- 2018/07/26 00:00 [revised] PHST- 2018/08/17 00:00 [accepted] PHST- 2018/10/02 06:00 [entrez] PHST- 2018/10/03 06:00 [pubmed] PHST- 2018/10/03 06:00 [medline] AID - S0021-9150(18)31307-8 [pii] AID - 10.1016/j.atherosclerosis.2018.08.013 [doi] PST - ppublish SO - Atherosclerosis. 2018 Oct;277:413-418. doi: 10.1016/j.atherosclerosis.2018.08.013. PMID- 30270054 OWN - NLM STAT- In-Data-Review LR - 20190115 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 277 DP - 2018 Oct TI - Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). PG - 234-255 LID - S0021-9150(18)31359-5 [pii] LID - 10.1016/j.atherosclerosis.2018.08.051 [doi] AB - BACKGROUND AND AIMS: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in approximately 2/3 countries. Lipoprotein-apheresis is offered in approximately 60% countries, although access is limited. CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. CN - EAS Familial Hypercholesterolaemia Studies Collaboration CN - EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) Investigators LA - eng PT - Journal Article PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 OTO - NOTNLM OT - FHSC OT - Familial hypercholesterolaemia OT - Primary dyslipidaemia IR - Vallejo-Vaz AJ FIR - Vallejo-Vaz, Antonio J IRAD- Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom. Electronic address: a.vallejo-vaz@imperial.ac.uk. IR - De Marco M FIR - De Marco, Martina IRAD- Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom. Electronic address: m.de-marco12@imperial.ac.uk. IR - Stevens CAT FIR - Stevens, Christophe A T IRAD- Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom. IR - Akram A FIR - Akram, Asif IRAD- Living Goods, Nairobi, Kenya. IR - Freiberger T FIR - Freiberger, Tomas IRAD- Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic. IR - Hovingh GK FIR - Hovingh, G Kees IRAD- Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands. IR - Kastelein JJP FIR - Kastelein, John J P IRAD- Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands. IR - Mata P FIR - Mata, Pedro IRAD- Fundacion Hipercolesterolemia Familiar, Madrid, Spain. IR - Raal FJ FIR - Raal, Frederick J IRAD- Division of Endocrinology & Metabolism, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. IR - Santos RD FIR - Santos, Raul D IRAD- Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil; Hospital Israelita Albert Einstein, Sao Paulo, Brazil. IR - Soran H FIR - Soran, Handrean IRAD- University Department of Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom. IR - Watts GF FIR - Watts, Gerald F IRAD- School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia; FH Australasia Network (FHAN), Australia. IR - Abifadel M FIR - Abifadel, Marianne IRAD- Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pole Technologie-Sante, Saint Joseph University, Beirut, Lebanon. IR - Aguilar-Salinas CA FIR - Aguilar-Salinas, Carlos A IRAD- Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico. IR - Al-Khnifsawi M FIR - Al-Khnifsawi, Mutaz IRAD- Al-Qadisiyah University, Faculty of Medicine, Department of Internal Medicine, Diwaniya City, Iraq. IR - AlKindi FA FIR - AlKindi, Fahad A IRAD- Hamad Medical Corporation, Heart Hospital, Doha, Qatar. IR - Alnouri F FIR - Alnouri, Fahad IRAD- Cardiovascular Prevention Unit, Prince Sultan Cardiac Centre Riyadh, Riyadh, Saudi Arabia. IR - Alonso R FIR - Alonso, Rodrigo IRAD- Clinica Las Condes, Santiago de Chile, Chile. IR - Al-Rasadi K FIR - Al-Rasadi, Khalid IRAD- Sultan Qaboos University Hospital, Muscat, Oman. IR - Al-Sarraf A FIR - Al-Sarraf, Ahmad IRAD- Laboratory Department, Kuwait Cancer Control Centre, Kuwait City, Kuwait. IR - Ashavaid TF FIR - Ashavaid, Tester F IRAD- P. D Hinduja National Hospital and Medical Research Centre, Mumbai, India. IR - Binder CJ FIR - Binder, Christoph J IRAD- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. IR - Bogsrud MP FIR - Bogsrud, Martin P IRAD- Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. IR - Bourbon M FIR - Bourbon, Mafalda IRAD- Unidade I&D, Grupo de Investigacao Cardiovascular, Departamento de Promocao da Saude e Doencas Nao Transmissiveis, Instituto Nacional de Saude Doutor Ricardo Jorge, Lisboa, Portugal; Faculty of Sciences, Biosystems & Integrative Sciences Institute (BioISI), University of Lisboa, Lisboa, Portugal. IR - Bruckert E FIR - Bruckert, Eric IRAD- Department of Endocrinology, Institut E3M et IHU Cardiometabolique (ICAN), Hopital Pitie Salpetriere, Paris, France. IR - Chlebus K FIR - Chlebus, Krzysztof IRAD- First Department of Cardiology, Medical University of Gdansk, Gdansk, Poland; Clinical Centre of Cardiology, University Clinical Centre, Gdansk, Poland. IR - Corral P FIR - Corral, Pablo IRAD- Pharmacology Department, School of Medicine, FASTA University, Mar del Plata, Argentina. IR - Descamps O FIR - Descamps, Olivier IRAD- Centres Hospitaliers Jolimont, Haine Saint-Paul, Belgium. IR - Durst R FIR - Durst, Ronen IRAD- Cardiology Department and Centre for Treatment and Prevention of Atherosclerosis, Hadassah Hebrew University Medical Centre, Jerusalem, Israel. IR - Ezhov M FIR - Ezhov, Marat IRAD- National Cardiology Research Centre, Ministry of Health of the Russian Federation, Russia. IR - Fras Z FIR - Fras, Zlatko IRAD- University Medical Centre Ljubljana, Division of Medicine, Preventive Cardiology Unit, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. IR - Genest J FIR - Genest, Jacques IRAD- Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. IR - Groselj U FIR - Groselj, Urh IRAD- University Medical Centre Ljubljana, University Children's Hospital, Department of Endocrinology, Diabetes and Metabolism, Ljubljana, Slovenia. IR - Harada-Shiba M FIR - Harada-Shiba, Mariko IRAD- National Cerebral and Cardiovascular Centre Research Institute, Suita, Osaka, Japan. IR - Kayikcioglu M FIR - Kayikcioglu, Meral IRAD- Ege University Medical School, Department of Cardiology, Izmir, Turkey. IR - Lalic K FIR - Lalic, Katarina IRAD- Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia. IR - Lam CSP FIR - Lam, Carolyn S P IRAD- National Heart Centre, Singapore; Duke-NUS Medical School, Singapore. IR - Latkovskis G FIR - Latkovskis, Gustavs IRAD- Research Institute of Cardiology and Regenerative Medicine, Faculty of Medicine, University of Latvia, Pauls Stradins Clinical University Hospital, Riga, Latvia. IR - Laufs U FIR - Laufs, Ulrich IRAD- Klinik und Poliklinikfur Kardiologie, Universitatsklinikum Leipzig, Germany. IR - Liberopoulos E FIR - Liberopoulos, Evangelos IRAD- Faculty of Medicine, University of Ioannina, Ioannina, Greece. IR - Lin J FIR - Lin, Jie IRAD- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. IR - Maher V FIR - Maher, Vincent IRAD- Advanced Lipid Management and Research (ALMAR) Centre, Ireland. IR - Majano N FIR - Majano, Nelson IRAD- Hospital Militar de Caracas, Caracas, Venezuela. IR - Marais AD FIR - Marais, A David IRAD- University of Cape Town and National Health Laboratory Service, Cape Town, South Africa. IR - Marz W FIR - Marz, Winfried IRAD- Medizinische Klinik V (Nephrologie, Hypertensiologie, Rheumatologie, Endokrinologie, Diabetologie), Medizinische Fakultat Mannheim der Universitat Heidelberg, Mannheim, Germany; Klinisches Institutfur Medizinische und Chemische Labordiagnostik, Medizinische Universitat Graz, Graz, Austria; Synlab Akademie, Synlab Holding Deutschland GmbH, Mannheim und Augsburg, Germany; D-A-CH-Gesellschaft Pravention von Herz-Kreislauf-Erkrankungen e.V., Hamburg, Germany. IR - Mirrakhimov E FIR - Mirrakhimov, Erkin IRAD- Kyrgyz State Medical Academy, Centre of Cardiology and Internal Diseases, Biskek, Kyrgizstan. IR - Miserez AR FIR - Miserez, Andre R IRAD- Diagene Research Institute, Swiss FH Center, Reinach, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland. IR - Mitchenko O FIR - Mitchenko, Olena IRAD- Dyslipidemia Department, State Institution National Scientific Centre "The M.D. Strazhesko Institute of Cardiology National Academy of Medical Sciences of Ukraine", Kiev, Ukraine. IR - Nawawi HM FIR - Nawawi, Hapizah M IRAD- Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM) and Faculty of Medicine Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh, Selangor, Malaysia. IR - Nordestgaard BG FIR - Nordestgaard, Borge G IRAD- Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. IR - Paragh G FIR - Paragh, Gyorgy IRAD- Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. IR - Petrulioniene Z FIR - Petrulioniene, Zaneta IRAD- Vilnius University, Faculty of Medicine, Vilnius, Lithuania; Clinic of Cardiac and Vascular Diseases, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. IR - Pojskic B FIR - Pojskic, Belma IRAD- Cantonal Hospital Zenica, Bosnia and Herzegovina. IR - Postadzhiyan A FIR - Postadzhiyan, Arman IRAD- Bulgarian Society of Cardiology, Medical University of Sofia, Sofia, Bulgaria. IR - Reda A FIR - Reda, Ashraf IRAD- Cardiology, Menofia University, Egypt; Egyptian Association of Vernacular Biology and Atherosclerosis (EAVA), Egypt. IR - Reiner Z FIR - Reiner, Zeljko IRAD- Department of Internal Medicine, Division of Metabolic Diseases, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia. IR - Sadoh WE FIR - Sadoh, Wilson E IRAD- Cardiology Unit, Department of Child Health, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria. IR - Sahebkar A FIR - Sahebkar, Amirhossein IRAD- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. IR - Shehab A FIR - Shehab, Abdullah IRAD- Department of Internal Medicine, United Arab Emirates University-College of Medicine and Health Sciences, AlAin, United Arab Emirates. IR - Shek AB FIR - Shek, Aleksander B IRAD- CAD and Atherosclerosis Laboratory, Republican Specialized Centre of Cardiology (RSCC), Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan. IR - Stoll M FIR - Stoll, Mario IRAD- Honorary Commission for Cardiovascular Health (CHSCV), Montevideo, Uruguay. IR - Su TC FIR - Su, Ta-Chen IRAD- Departments of Internal Medicine and Environmental & Occupational Medicine, Cardiovascular Centre, National Taiwan University Hospital, Taipei, Taiwan. IR - Subramaniam T FIR - Subramaniam, Tavintharan IRAD- Diabetes Centre, Admiralty Medical Centre, Singapore; Division of Endocrinology, Khoo Teck Puat Hospital, Singapore; Clinical Research Unit, Khoo Teck Puat Hospital, Singapore. IR - Susekov AV FIR - Susekov, Andrey V IRAD- Faculty of Clinical Pharmacology and Therapeutics, Academy for Postgraduate Medical Education and Central Clinical Hospital, Academy of Medical Science, Moscow, Russia. IR - Symeonides P FIR - Symeonides, Phivos IRAD- Hippocrateon Private Hospital, Nicosia, Cyprus. IR - Tilney M FIR - Tilney, Myra IRAD- Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Malta; Lipid Clinic, Mater Dei Hospital, Malta. IR - Tomlinson B FIR - Tomlinson, Brian IRAD- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. IR - Truong TH FIR - Truong, Thanh-Huong IRAD- Department of Cardiology, Hanoi Medical University, Hanoi, Viet Nam; Vietnam National Heart Institute, Bach Mai Hospital, Hanoi, Viet Nam. IR - Tselepis AD FIR - Tselepis, Alexandros D IRAD- Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece. IR - Tybjaerg-Hansen A FIR - Tybjaerg-Hansen, Anne IRAD- Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Denmark. IR - Vazquez-Cardenas A FIR - Vazquez-Cardenas, Alejandra IRAD- Facultad de Medicina, Universidad Autonoma de Guadalajara, Guadalajara, Mexico. IR - Viigimaa M FIR - Viigimaa, Margus IRAD- Centre for Cardiovascular Medicine, North Estonia Medical Centre, Tallinn University of Technology, Tallinn, Estonia. IR - Vohnout B FIR - Vohnout, Branislav IRAD- Institute of Nutrition, FOZOS, Slovak Medical University, Bratislava, Slovakia; Coordination Centre for Familial Hyperlipoproteinemias, Slovak Medical University, Bratislava, Slovakia. IR - Widen E FIR - Widen, Elisabeth IRAD- Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. IR - Yamashita S FIR - Yamashita, Shizuya IRAD- Rinku General Medical Centre and Osaka University Graduate School of Medicine, Osaka, Japan. IR - Banach M FIR - Banach, Maciej IRAD- Department of Hypertension, Medical University of Lodz, Lodz, Poland. IR - Gaita D FIR - Gaita, Dan IRAD- Universitatea de Medicina si Farmacie Victor Babes din Timisoara, Romania. IR - Jiang L FIR - Jiang, Lixin IRAD- National Clinical Research Centre of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Beijing, China. IR - Nilsson L FIR - Nilsson, Lennart IRAD- Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden. IR - Santos LE FIR - Santos, Lourdes E IRAD- Cardinal Santos Medical Centre, University of the Philippines - Philippine General Hospital (UP-PGH), Philippines. IR - Schunkert H FIR - Schunkert, Heribert IRAD- Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Deutsches Zentrumfur Herz- und Kreislauferkrankungen (DZHK), Munich Heart Alliance, Germany. IR - Tokgozoglu L FIR - Tokgozoglu, Lale IRAD- Department of Cardiology, Hacettepe University, Ankara, Turkey. IR - Car J FIR - Car, Josip IRAD- Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom; Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. IR - Catapano AL FIR - Catapano, Alberico L IRAD- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. IR - Ray KK FIR - Ray, Kausik K IRAD- Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom. EDAT- 2018/10/03 06:00 MHDA- 2018/10/03 06:00 CRDT- 2018/10/02 06:00 PHST- 2018/08/15 00:00 [received] PHST- 2018/08/30 00:00 [revised] PHST- 2018/08/31 00:00 [accepted] PHST- 2018/10/02 06:00 [entrez] PHST- 2018/10/03 06:00 [pubmed] PHST- 2018/10/03 06:00 [medline] AID - S0021-9150(18)31359-5 [pii] AID - 10.1016/j.atherosclerosis.2018.08.051 [doi] PST - ppublish SO - Atherosclerosis. 2018 Oct;277:234-255. doi: 10.1016/j.atherosclerosis.2018.08.051. PMID- 30212680 OWN - NLM STAT- In-Data-Review LR - 20181001 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 277 DP - 2018 Oct TI - Use of proton pump inhibitors and risk of ischemic events in the general population. PG - 123-129 LID - S0021-9150(18)31344-3 [pii] LID - 10.1016/j.atherosclerosis.2018.08.035 [doi] AB - BACKGROUND AND AIMS: A potential increased risk of cardiovascular events has been suggested for proton pump inhibitors (PPIs), the most commonly prescribed drugs for the management of upper gastrointestinal disorders. We aimed to estimate the risk of hospitalization for cardio/cerebrovascular (CV) events in a cohort of incident PPI users. METHODS: A nested case-control study was carried out using regional healthcare utilization databases. For each case (hospitalization for non-haemorrhagic CV event), up-to-five controls randomly selected from the cohort were matched by gender, age at cohort entry, and index date. Exposure was estimated as recency of therapy (current, recent and past users) and number of days covered. Adjusted conditional logistic regression was used to estimate the association between exposure and outcome. RESULTS: Among new PPI users, we identified 17,832 cases and 89,160 controls (males 64.9%; mean age 58.9 years). Cases showed a significantly higher prevalence of use of drugs for diabetes, hypertension and hypercholesterolemia than controls. Risk of CV events was significantly higher for current (OR 1.61; 95%CI 1.55-1.68) and recent users (OR 1.15; 95%CI 1.06-1.26) compared to past users. Analogous results were found stratifying for cardiovascular (ORcurrent 1.71; 95%CI 1.63-1.81) and cerebrovascular events (ORcurrent 1.43; 95%CI 1.34-1.54). The increased risk was confirmed in subgroups by antithrombotic, statin use, or exposure duration. The same analysis for H2-antagonists use showed no significant results. CONCLUSIONS: In primary care setting, PPI use was independently associated with increased risk of first-time cardiovascular event, consistent with the evidence that PPIs adversely impact vascular function, underlying the need to promote appropriate prescribing of these drugs. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. Electronic address: manuela.casula@unimi.it. FAU - Scotti, Lorenza AU - Scotti L AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Galimberti, Federica AU - Galimberti F AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Mozzanica, Francesco AU - Mozzanica F AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica, Via Milanese 300, 20099, Sesto S. Giovanni (MI), Italy. LA - eng PT - Journal Article DEP - 20180827 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 OTO - NOTNLM OT - Cardio/cerebrovascular events OT - Case-control study OT - Databases OT - Proton pump inhibitors EDAT- 2018/09/14 06:00 MHDA- 2018/09/14 06:00 CRDT- 2018/09/14 06:00 PHST- 2018/03/23 00:00 [received] PHST- 2018/07/31 00:00 [revised] PHST- 2018/08/24 00:00 [accepted] PHST- 2018/09/14 06:00 [pubmed] PHST- 2018/09/14 06:00 [medline] PHST- 2018/09/14 06:00 [entrez] AID - S0021-9150(18)31344-3 [pii] AID - 10.1016/j.atherosclerosis.2018.08.035 [doi] PST - ppublish SO - Atherosclerosis. 2018 Oct;277:123-129. doi: 10.1016/j.atherosclerosis.2018.08.035. Epub 2018 Aug 27. PMID- 30165986 OWN - NLM STAT- In-Data-Review LR - 20180831 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 72 IP - 10 DP - 2018 Sep 4 TI - Impact of Lipids on Cardiovascular Health: JACC Health Promotion Series. PG - 1141-1156 LID - S0735-1097(18)35379-8 [pii] LID - 10.1016/j.jacc.2018.06.046 [doi] AB - People who maintain ideal cardiovascular heath have a low lifetime risk of cardiovascular disease. Therefore, encouraging people to achieve ideal cardiovascular health represents an important opportunity to improve the prevention of cardiovascular disease. However, preventing cardiovascular disease by promoting ideal cardiovascular health requires shifting the focus from treating disease after it develops to preventing cardiovascular events before they happen by slowing the progression of atherosclerosis. Because atherogenic lipoproteins play a central causal role in the initiation and progression of atherosclerosis, maintaining optimal lipid levels is necessary to achieve ideal cardiovascular health. This review describes the cumulative effect of lipid-carrying lipoproteins on the risk of cardiovascular disease, estimates the magnitude of the clinical benefit that can be achieved by maintaining optimal lipid levels, identifies the most effective timing for implementing strategies designed to achieve optimal lipid levels, and provides a clinical pathway to help people achieve the lipid levels necessary for ideal cardiovascular health. CI - Copyright (c) 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Ference, Brian A AU - Ference BA AD - Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, United Kingdom. FAU - Graham, Ian AU - Graham I AD - School of Medicine, Trinity College, Dublin, Ireland. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Department of Cardiology, Hacettepe University, Ankara, Turkey. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 OTO - NOTNLM OT - apolipoproteins OT - cholesterol OT - low-density lipoproteins OT - population OT - risk OT - total burden EDAT- 2018/09/01 06:00 MHDA- 2018/09/01 06:00 CRDT- 2018/09/01 06:00 PHST- 2018/02/19 00:00 [received] PHST- 2018/06/03 00:00 [revised] PHST- 2018/06/26 00:00 [accepted] PHST- 2018/09/01 06:00 [entrez] PHST- 2018/09/01 06:00 [pubmed] PHST- 2018/09/01 06:00 [medline] AID - S0735-1097(18)35379-8 [pii] AID - 10.1016/j.jacc.2018.06.046 [doi] PST - ppublish SO - J Am Coll Cardiol. 2018 Sep 4;72(10):1141-1156. doi: 10.1016/j.jacc.2018.06.046. PMID- 30177370 OWN - NLM STAT- MEDLINE DCOM- 20190108 LR - 20190108 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 35 DP - 2018 Sep TI - Epidemiology of cardiovascular risk factors in two population-based studies. PG - e14-e20 LID - S1567-5688(18)30553-1 [pii] LID - 10.1016/j.atherosclerosissup.2018.08.003 [doi] AB - We aimed to compare cardiovascular risk factors prevalence in Italy and Russia through cross-sectional database analysis. The study has been based on data from ESSE-RF and from baseline of PLIC study, two population-based epidemiological studies aimed to investigate prevalence of risk factors and evaluating contribution of traditional and new risk factors into morbidity and cardiovascular mortality. A total of 2203 patients with left and right intima-media thickness (IMT) measurements constituted the source population (1205 from PLIC study and 998 from ESSE-RF study). Sample of ESSE-RF study had slightly more diabetic and hypertensive individuals, while the percentage of subjects with high cholesterol value was lower than in the other sample (67.1% vs 79.9%). The median LDL-C value was higher among individuals not treated with statins in the PLIC sample (p<0.001), while was comparable among subjects receiving statin therapy. On the other hand, the percentage of individuals with positive cardiovascular history was higher in ESSE-RF sample. This could also explain the higher mean IMT value (0.71+/-0.17 vs 0.63+/-0.13) in the whole sample, and among patients without past cardiovascular events (regardless of statin treatment), despite some differences in major risk factors. Despite Russian and Italian populations are culturally and geographically different, they are not so different based on characteristics analyzed. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Olmastroni, Elena AU - Olmastroni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Shlyakhto, Evgeny V AU - Shlyakhto EV AD - Almazov National Medical Research Centre, Saint Petersburg, Russia. FAU - Konradi, Aleksandra O AU - Konradi AO AD - Almazov National Medical Research Centre, Saint Petersburg, Russia. FAU - Rotar, Oxana P AU - Rotar OP AD - Almazov National Medical Research Centre, Saint Petersburg, Russia. FAU - Alieva, Asiiat S AU - Alieva AS AD - Almazov National Medical Research Centre, Saint Petersburg, Russia. FAU - Boyarinova, Maria A AU - Boyarinova MA AD - Almazov National Medical Research Centre, Saint Petersburg, Russia. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy; S.I.S.A. Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Grigore, Liliana AU - Grigore L AD - S.I.S.A. Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; IRCCS MultiMedica Hospital, Via Milanese 300, 20099, Sesto S. Giovanni, Milan, Italy. FAU - Pellegatta, Fabio AU - Pellegatta F AD - S.I.S.A. Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; IRCCS MultiMedica Hospital, Via Milanese 300, 20099, Sesto S. Giovanni, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica Hospital, Via Milanese 300, 20099, Sesto S. Giovanni, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20180825 PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adult MH - Aged MH - Biomarkers/blood MH - Blood Glucose/analysis MH - Blood Pressure MH - Cardiovascular Diseases/diagnosis/*epidemiology/mortality MH - Carotid Artery Diseases/diagnostic imaging/epidemiology MH - Carotid Intima-Media Thickness MH - Cholesterol/blood MH - Comorbidity MH - Cross-Sectional Studies MH - Databases, Factual MH - Diabetes Mellitus/diagnosis/epidemiology MH - Female MH - Humans MH - Hypercholesterolemia/diagnosis/epidemiology MH - Hypertension/diagnosis/epidemiology MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Prevalence MH - Risk Assessment MH - Risk Factors MH - Russia/epidemiology OTO - NOTNLM OT - Cardiovascular risk factors OT - Epidemiology OT - Intima-media thickness EDAT- 2018/09/05 06:00 MHDA- 2019/01/09 06:00 CRDT- 2018/09/05 06:00 PHST- 2018/09/05 06:00 [pubmed] PHST- 2019/01/09 06:00 [medline] PHST- 2018/09/05 06:00 [entrez] AID - S1567-5688(18)30553-1 [pii] AID - 10.1016/j.atherosclerosissup.2018.08.003 [doi] PST - ppublish SO - Atheroscler Suppl. 2018 Sep;35:e14-e20. doi: 10.1016/j.atherosclerosissup.2018.08.003. Epub 2018 Aug 25. PMID- 30169643 OWN - NLM STAT- Publisher LR - 20180831 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) DP - 2018 Aug 28 TI - Why is hypercholesterolaemia so prevalent? A view from evolutionary medicine. LID - 10.1093/eurheartj/ehy479 [doi] FAU - Laufs, Ulrich AU - Laufs U AD - Klinik und Poliklinik fur Kardiologie; Universitatsklinikum Leipzig, Liebigstr. 20, 04103 Leipzig, Germany. FAU - Dent, Ricardo AU - Dent R AD - Amgen Inc., Thousand Oaks, CA 91320, USA. FAU - Kostenuik, Paul J AU - Kostenuik PJ AD - University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA. AD - Phylon Pharma Services, Newbury Park, CA, USA. FAU - Toth, Peter P AU - Toth PP AD - CGH Medical Center, Sterling, IL 61081, USA. AD - Johns Hopkins University School of Medicine, Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milan, Italy. AD - Multimedica IRCCS Via Milanese, 300, 20099 Sesto San Giovanni, Milano, Italy. FAU - Chapman, M John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France. LA - eng PT - Journal Article DEP - 20180828 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 EDAT- 2018/09/01 06:00 MHDA- 2018/09/01 06:00 CRDT- 2018/09/01 06:00 PHST- 2018/02/08 00:00 [received] PHST- 2018/08/23 00:00 [accepted] PHST- 2018/09/01 06:00 [entrez] PHST- 2018/09/01 06:00 [pubmed] PHST- 2018/09/01 06:00 [medline] AID - 5086122 [pii] AID - 10.1093/eurheartj/ehy479 [doi] PST - aheadofprint SO - Eur Heart J. 2018 Aug 28. pii: 5086122. doi: 10.1093/eurheartj/ehy479. PMID- 30082772 OWN - NLM STAT- MEDLINE DCOM- 20190107 LR - 20190329 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 9 IP - 1 DP - 2018 Aug 6 TI - Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation. PG - 3083 LID - 10.1038/s41467-018-05322-1 [doi] AB - Cholesterol homeostasis has a pivotal function in regulating immune cells. Here we show that apolipoprotein E (apoE) deficiency leads to the accumulation of cholesterol in the cell membrane of dendritic cells (DC), resulting in enhanced MHC-II-dependent antigen presentation and CD4(+) T-cell activation. Results from WT and apoE KO bone marrow chimera suggest that apoE from cells of hematopoietic origin has immunomodulatory functions, regardless of the onset of hypercholesterolemia. Humans expressing apoE4 isoform (epsilon4/3-epsilon4/4) have increased circulating levels of activated T cells compared to those expressing WT apoE3 (epsilon3/3) or apoE2 isoform (epsilon2/3-epsilon2/2). This increase is caused by enhanced antigen-presentation by apoE4-expressing DCs, and is reversed when these DCs are incubated with serum containing WT apoE3. In summary, our study identifies myeloid-produced apoE as a key physiological modulator of DC antigen presentation function, paving the way for further explorations of apoE as a tool to improve the management of immune diseases. FAU - Bonacina, Fabrizia AU - Bonacina F AUID- ORCID: 0000-0002-2611-1177 AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. FAU - Coe, David AU - Coe D AD - William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Wang, Guosu AU - Wang G AD - William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Longhi, Maria P AU - Longhi MP AUID- ORCID: 0000-0003-1854-4594 AD - William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, 20092, Italy. FAU - Moregola, Annalisa AU - Moregola A AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, 20092, Italy. FAU - Uboldi, Patrizia AU - Uboldi P AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. FAU - Pellegatta, Fabio AU - Pellegatta F AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, 20092, Italy. FAU - Grigore, Liliana AU - Grigore L AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, 20092, Italy. FAU - Da Dalt, Lorenzo AU - Da Dalt L AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. FAU - Annoni, Andrea AU - Annoni A AD - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy. FAU - Gregori, Silvia AU - Gregori S AUID- ORCID: 0000-0002-3517-9683 AD - San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy. FAU - Xiao, Qingzhong AU - Xiao Q AD - William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Caruso, Donatella AU - Caruso D AUID- ORCID: 0000-0003-2115-778X AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. FAU - Mitro, Nico AU - Mitro N AUID- ORCID: 0000-0002-5000-3619 AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. AD - IRCSS Multimedica, Milan, 20138, Italy. FAU - Marelli-Berg, Federica M AU - Marelli-Berg FM AD - William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Norata, Giuseppe D AU - Norata GD AUID- ORCID: 0000-0002-6081-1257 AD - Department of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan, 20133, Italy. danilo.norata@unimi.it. AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, 20092, Italy. danilo.norata@unimi.it. LA - eng GR - FS/13/49/30421/British Heart Foundation/United Kingdom GR - RG/14/2/30616/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180806 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Apolipoprotein E4) RN - 0 (Apolipoproteins E) RN - 0 (Fatty Acids) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Oxysterols) RN - 0 (Phospholipids) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - *Antigen Presentation MH - Apolipoprotein E4/genetics MH - Apolipoproteins E/*genetics MH - Bone Marrow Cells/cytology MH - Cell Differentiation MH - Cell Movement MH - Cholesterol/metabolism MH - Dendritic Cells/cytology/*metabolism MH - Fatty Acids/metabolism MH - Female MH - Hematopoietic Stem Cells/cytology MH - Histocompatibility Antigens Class II MH - Humans MH - Hypercholesterolemia/metabolism MH - *Lymphocyte Activation MH - Major Histocompatibility Complex MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myeloid Cells/*metabolism MH - Oxysterols/chemistry/metabolism MH - Phospholipids/chemistry MH - T-Lymphocytes/*metabolism PMC - PMC6079066 EDAT- 2018/08/08 06:00 MHDA- 2019/01/08 06:00 CRDT- 2018/08/08 06:00 PHST- 2017/09/06 00:00 [received] PHST- 2018/06/24 00:00 [accepted] PHST- 2018/08/08 06:00 [entrez] PHST- 2018/08/08 06:00 [pubmed] PHST- 2019/01/08 06:00 [medline] AID - 10.1038/s41467-018-05322-1 [doi] AID - 10.1038/s41467-018-05322-1 [pii] PST - epublish SO - Nat Commun. 2018 Aug 6;9(1):3083. doi: 10.1038/s41467-018-05322-1. PMID- 29868825 OWN - NLM STAT- In-Data-Review LR - 20180716 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 27 DP - 2018 Jul 14 TI - PCSK9 inhibition and Lp(a) reduction: another piece of the puzzle? PG - 2586-2588 LID - 10.1093/eurheartj/ehy311 [doi] FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 EDAT- 2018/06/06 06:00 MHDA- 2018/06/06 06:00 CRDT- 2018/06/06 06:00 PHST- 2018/06/06 06:00 [pubmed] PHST- 2018/06/06 06:00 [medline] PHST- 2018/06/06 06:00 [entrez] AID - 5032458 [pii] AID - 10.1093/eurheartj/ehy311 [doi] PST - ppublish SO - Eur Heart J. 2018 Jul 14;39(27):2586-2588. doi: 10.1093/eurheartj/ehy311. PMID- 29718253 OWN - NLM STAT- In-Data-Review LR - 20181114 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 27 DP - 2018 Jul 14 TI - Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. PG - 2526-2539 LID - 10.1093/eurheartj/ehy182 [doi] AB - Aims: To objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract. Methods and results: A literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin >/=6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies. Conclusion: Long-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects. FAU - Mach, Francois AU - Mach F AD - Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4 1205 Geneva, Switzerland. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. FAU - Wiklund, Olov AU - Wiklund O AD - Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. AD - Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Corsini, Alberto AU - Corsini A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy. FAU - Bruckert, Eric AU - Bruckert E AD - National Institute for Health and Medical Research (INSERM) UMRS1166, Department of Endocrinology-Metabolism, ICAN-Institute of CardioMetabolism and Nutrition, AP-HP, Hopital de la Pitie, Paris, France. FAU - De Backer, Guy AU - De Backer G AD - Department of Public Health, University Hospital Ghent, Ghent, Belgium. FAU - Hegele, Robert A AU - Hegele RA AD - Department of Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Jacobson, Terry A AU - Jacobson TA AD - Department of Medicine, Emory University, Atlanta, GA, USA. FAU - Krauss, Ronald M AU - Krauss RM AD - Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA, USA. FAU - Laufs, Ulrich AU - Laufs U AD - Department of Cardiology, University of Leipzig, Leipzig, Germany. FAU - Leiter, Lawrence A AU - Leiter LA AD - Li Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, Toronto, ON, Canada. FAU - Marz, Winfried AU - Marz W AD - Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany. AD - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. AD - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark. FAU - Raal, Frederick J AU - Raal FJ AD - Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. FAU - Roden, Michael AU - Roden M AD - German Center for Diabetes Research (DZD), Munchen-Neuherberg, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Dusseldorf, Germany. AD - Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Dusseldorf, Dusseldorf, Germany. FAU - Santos, Raul D AU - Santos RD AD - Hospital Israelita Albert Einstein, Sao Paulo, Brazil. AD - Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. FAU - Stein, Evan A AU - Stein EA AD - Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA. FAU - Stroes, Erik S AU - Stroes ES AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. FAU - Thompson, Paul D AU - Thompson PD AD - Hartford Hospital, Hartford, CT, USA. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Department of Cardiology, Hacettepe University, Ankara, Turkey. FAU - Vladutiu, Georgirene D AU - Vladutiu GD AD - Jacobs School of Medicine & Biomedical Sciences, University at Buffalo, The State University of New York, New York, USA. FAU - Gencer, Baris AU - Gencer B AD - Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4 1205 Geneva, Switzerland. FAU - Stock, Jane K AU - Stock JK AD - European Atherosclerosis Society, Gothenburg, Sweden. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA. FAU - Chapman, M John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), and University of Pierre and Marie Curie-Paris 6, Pitie Salpetriere, Paris, France. CN - European Atherosclerosis Society Consensus Panel LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 PMC - PMC6047411 EDAT- 2018/05/03 06:00 MHDA- 2018/05/03 06:00 CRDT- 2018/05/03 06:00 PHST- 2017/10/09 00:00 [received] PHST- 2018/03/22 00:00 [accepted] PHST- 2018/05/03 06:00 [pubmed] PHST- 2018/05/03 06:00 [medline] PHST- 2018/05/03 06:00 [entrez] AID - 4987130 [pii] AID - 10.1093/eurheartj/ehy182 [doi] PST - ppublish SO - Eur Heart J. 2018 Jul 14;39(27):2526-2539. doi: 10.1093/eurheartj/ehy182. PMID- 29579192 OWN - NLM STAT- In-Data-Review LR - 20180716 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 27 DP - 2018 Jul 14 TI - New prospects for PCSK9 inhibition? PG - 2600-2601 LID - 10.1093/eurheartj/ehy147 [doi] FAU - Landmesser, Ulf AU - Landmesser U AD - Department of Cardiology, Charite - Universitatsmedizin Berlin (CBF), and Institute of Health (BIH), Berlin, Germany. FAU - Chapman, M John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), University of Pierre and Marie Curie, Pitie-Salpetriere Hospital, Paris, France. FAU - Stock, Jane K AU - Stock JK AD - European Atherosclerosis Society, Gothenburg, Sweden. FAU - Amarenco, Pierre AU - Amarenco P AD - Department of Neurology and Stroke Centre, Bichat Hospital, Paris-Diderot-Sorbonne University, Paris, France. FAU - Belch, Jill J F AU - Belch JJF AD - Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee, UK. FAU - Boren, Jan AU - Boren J AD - Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, and Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Farnier, Michel AU - Farnier M AD - Lipid Clinic, Point Medical, and Department of Cardiology, CHU Dijon-Bourgogne, Dijon, France. FAU - Ference, Brian A AU - Ference BA AD - Division of Cardiovascular Medicine, Division of Translational Research and Clinical Epidemiology, Wayne State University School of Medicine, Detroit, MI, USA. FAU - Gielen, Stephan AU - Gielen S AD - Martin-Luther-University Halle/Wittenberg, University Hospital, Department of Internal Medicine III, Halle/Saale, Germany. FAU - Graham, Ian AU - Graham I AD - Trinity College Dublin, Ireland. FAU - Grobbee, Diederick E AU - Grobbee DE AD - Julius Global Health, the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Hovingh, G Kees AU - Hovingh GK AD - Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands. FAU - Luscher, Thomas F AU - Luscher TF AD - University Heart Center, Department of Cardiology, University Hospital Zurich, and Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland. FAU - Piepoli, Massimo F AU - Piepoli MF AD - G Da Saliceto Hospital, Heart Failure Unit, Cardiac Department, Piacenza, Italy. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London, UK. FAU - Stroes, Erik S AU - Stroes ES AD - Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands. FAU - Wiklund, Olov AU - Wiklund O AD - Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Windecker, Stephan AU - Windecker S AD - Department of Cardiology, Swiss Cardiovascular Center, University Hospital, Bern, Switzerland. FAU - Zamorano, Jose Luis AU - Zamorano JL AD - Department of Cardiology, University Hospital Ramon y Cajal, Madrid, Spain. FAU - Pinto, Fausto AU - Pinto F AD - Cardiology Department, CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Portugal. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Department of Cardiology, Hacettepe University, Ankara, Turkey. FAU - Bax, Jeroen J AU - Bax JJ AD - Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan and Multimedica IRCSS Milano, Italy. CN - European Society of Cardiology/European Atherosclerosis Society Task Force LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 EDAT- 2018/03/27 06:00 MHDA- 2018/03/27 06:00 CRDT- 2018/03/27 06:00 PHST- 2018/03/27 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2018/03/27 06:00 [entrez] AID - 4951530 [pii] AID - 10.1093/eurheartj/ehy147 [doi] PST - ppublish SO - Eur Heart J. 2018 Jul 14;39(27):2600-2601. doi: 10.1093/eurheartj/ehy147. PMID- 29020411 OWN - NLM STAT- In-Data-Review LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 27 DP - 2018 Jul 14 TI - Reduction of low density lipoprotein-cholesterol and cardiovascular events with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins: an analysis of FOURIER, SPIRE, and the Cholesterol Treatment Trialists Collaboration. PG - 2540-2545 LID - 10.1093/eurheartj/ehx450 [doi] FAU - Ference, Brian A AU - Ference BA AD - Division of Translational Research and Clinical Epidemiology, Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, MI, USA. FAU - Cannon, Christopher P AU - Cannon CP AD - Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA. FAU - Landmesser, Ulf AU - Landmesser U AD - Department of Cardiology, Charite Universitats Medizin Berlin, Campus Benjamin Franklin, Berlin, Germany. FAU - Luscher, Thomas F AU - Luscher TF AD - Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, University of Milan, Via Balzaretti, 9, 20133 Milan, Italy. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College, London, UK. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 PMC - PMC6047439 EDAT- 2017/10/12 06:00 MHDA- 2017/10/12 06:00 CRDT- 2017/10/12 06:00 PHST- 2017/02/01 00:00 [received] PHST- 2017/07/14 00:00 [accepted] PHST- 2017/10/12 06:00 [pubmed] PHST- 2017/10/12 06:00 [medline] PHST- 2017/10/12 06:00 [entrez] AID - 4082634 [pii] AID - 10.1093/eurheartj/ehx450 [doi] PST - ppublish SO - Eur Heart J. 2018 Jul 14;39(27):2540-2545. doi: 10.1093/eurheartj/ehx450. PMID- 29879431 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1873-2194 (Electronic) IS - 0163-7827 (Linking) VI - 71 DP - 2018 Jul TI - High density lipoprotein cholesterol and cancer: Marker or causative? PG - 54-69 LID - S0163-7827(18)30007-9 [pii] LID - 10.1016/j.plipres.2018.06.001 [doi] AB - The relationship between high-density lipoproteins (HDLs), HDL-cholesterol (HDLC) and cancer incidence and mortality is controversial. Although most studies conducted so far, including well-designed prospective studies and meta-analyses, have revealed a significant inverse association between HDL-C levels and cancer risk, several confounding factors and opposite results showing either a direct or an inverse association between HDL-C levels and cancer mortality have hindered the possibility to derive definitive conclusions. Moreover, different lines of research also pointed out that this association might actually reflect an inverse causality, which would imply that low HDL-C levels merely represent an epiphenomenon of cancer-related inflammation and cancer cell renewal. Accordingly, the pharmacological increase of plasma HDL-C levels in large lipid modifying trials has not resulted in an amelioration of cancer-related outcomes. In such an intricate scenario, we conducted a comprehensive review of the literature with the aim to provide a wide perspective on the association between HDLs, mild and extreme changes in plasma HDL-C levels and cancer incidence and mortality, touching upon the certainties, the failures and the open issues in this intriguing area of research. CI - Copyright (c) 2018. Published by Elsevier Ltd. FAU - Pirro, Matteo AU - Pirro M AD - Unit of Internal Medicine, Department of Medicine, University of Perugia, Perugia, Italy. FAU - Ricciuti, Biagio AU - Ricciuti B AD - Department of Medical Oncology, S. Maria della Misericordia Hospital, Perugia, Italy. FAU - Rader, Daniel J AU - Rader DJ AD - Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Departments of Genetics and Medicine, Cardiovascular Institute, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS Multimedica Hospital, Sesto San Giovanni, Milan, Italy. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. Electronic address: maciejbanach77@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20180604 PL - England TA - Prog Lipid Res JT - Progress in lipid research JID - 7900832 RN - 0 (Biomarkers, Tumor) RN - 0 (Cholesterol, HDL) RN - 0 (Hypolipidemic Agents) SB - IM MH - Animals MH - Biomarkers, Tumor/*blood MH - Cardiovascular Diseases/blood/diagnosis MH - Cholesterol, HDL/*blood MH - Humans MH - Hypolipidemic Agents/therapeutic use MH - Lipid Metabolism/drug effects MH - Neoplasms/*blood/*diagnosis MH - Risk Assessment MH - Risk Factors OTO - NOTNLM OT - *Cancer OT - *Cholesterol OT - *HDL OT - *Hypoalphalipoproteinemia OT - *Mortality EDAT- 2018/06/08 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/06/08 06:00 PHST- 2018/02/10 00:00 [received] PHST- 2018/05/15 00:00 [revised] PHST- 2018/06/02 00:00 [accepted] PHST- 2018/06/08 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/06/08 06:00 [entrez] AID - S0163-7827(18)30007-9 [pii] AID - 10.1016/j.plipres.2018.06.001 [doi] PST - ppublish SO - Prog Lipid Res. 2018 Jul;71:54-69. doi: 10.1016/j.plipres.2018.06.001. Epub 2018 Jun 4. PMID- 29848265 OWN - NLM STAT- Publisher LR - 20180610 IS - 1875-533X (Electronic) IS - 0929-8673 (Linking) DP - 2018 May 29 TI - Biological consequences of dysfunctional HDL. LID - 10.2174/0929867325666180530110543 [doi] AB - Epidemiological studies have suggested an inverse correlation between high density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular disease. HDLs promote reverse cholesterol transport (RCT) and possess several putative atheroprotective functions, associated to the anti-inflammatory, anti-thrombotic and anti-oxidant properties as well as to the ability to support endothelial physiology. The assumption that increasing HDL-C levels would be beneficial on cardiovascular disease (CVD), however, has been questioned as, in most clinical trials, HDL-C-raising therapies did not result in improved cardiovascular outcomes. These findings, together with the observations from Mendelian randomization studies showing that polymorphisms mainly or solely associated with increased HDL-C levels did not decrease the risk of myocardial infarction, shift the focus from HDL-C levels toward HDL functional properties. Indeed, HDL from atherosclerotic patients not only exhibit impaired atheroprotective functions but also acquire pro-atherogenic properties and are referred to as "dysfunctional" HDL; this occurs even in the presence of normal or elevated HDL-C levels. Pharmacological approaches aimed at restoring HDL functions may therefore impact more significantly on CVD outcome than drugs used so far to increase HDL-C levels. Aims of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital Via M. Gorki 50 - Cinisello Balsamo, Milan. Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica Via Balzaretti, 9 - 20133 Milan. Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Center for the Study of Atherosclerosis, E. Bassini Hospital Via M. Gorki 50 - Cinisello Balsamo, Milan. Italy. LA - eng PT - Journal Article DEP - 20180529 PL - United Arab Emirates TA - Curr Med Chem JT - Current medicinal chemistry JID - 9440157 OTO - NOTNLM OT - * OT - *HDL subfractions OT - *HDL quality OT - *atherosclerosis OT - *cardiovascular disease OT - *dysfunctional HDL OT - *high density lipoprotein EDAT- 2018/06/01 06:00 MHDA- 2018/06/01 06:00 CRDT- 2018/06/01 06:00 PHST- 2017/10/02 00:00 [received] PHST- 2017/12/25 00:00 [revised] PHST- 2017/12/27 00:00 [accepted] PHST- 2018/06/01 06:00 [entrez] PHST- 2018/06/01 06:00 [pubmed] PHST- 2018/06/01 06:00 [medline] AID - CMC-EPUB-90786 [pii] AID - 10.2174/0929867325666180530110543 [doi] PST - aheadofprint SO - Curr Med Chem. 2018 May 29. pii: CMC-EPUB-90786. doi: 10.2174/0929867325666180530110543. PMID- 29609754 OWN - NLM STAT- MEDLINE DCOM- 20180918 LR - 20180918 IS - 1558-2264 (Electronic) IS - 0733-8651 (Linking) VI - 36 IP - 2 DP - 2018 May TI - Proprotein Convertase Subtilisin Kexin 9 Inhibitors. PG - 241-256 LID - S0733-8651(17)30156-X [pii] LID - 10.1016/j.ccl.2017.12.006 [doi] AB - High levels of low-density lipoprotein cholesterol (LDL-C) are directly associated with an increased risk of cardiovascular disease. Reducing LDL-C levels reduces the incidence of cardiovascular events. Several lipid-lowering approaches are available to achieve the LDL-C levels recommended by current guidelines, statins being the first-line therapy. However, many patients cannot achieve the recommended LDL-C levels with current therapies. The discovery of the role of proprotein convertase subtilisin kexin 9 (PCSK9) in the regulation of plasma LDL-C levels suggested it as a potential pharmacologic target and led to the development of PCSK9 inhibitors for the management of LDL-C levels. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Via M. Gorki, 50, Cinisello Balsamo, Milan 20092, Italy; IRCCS MultiMedica, Via Milanese, 300, Sesto S. Giovanni, Milan 20099, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS MultiMedica, Via Milanese, 300, Sesto S. Giovanni, Milan 20099, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, Milan 20133, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Cardiol Clin JT - Cardiology clinics JID - 8300331 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM MH - Anticholesteremic Agents/*therapeutic use MH - Cardiovascular Diseases/blood/*prevention & control MH - Cholesterol, LDL/*blood/drug effects MH - Humans MH - Proprotein Convertase 9/*antagonists & inhibitors OTO - NOTNLM OT - Alirocumab OT - Cardiovascular disease OT - Evolocumab OT - Hypercholesterolemia OT - LDL-C OT - Monoclonal antibodies OT - PCSK9 OT - Proprotein convertase subtilisin kexin 9 EDAT- 2018/04/04 06:00 MHDA- 2018/09/19 06:00 CRDT- 2018/04/04 06:00 PHST- 2018/04/04 06:00 [entrez] PHST- 2018/04/04 06:00 [pubmed] PHST- 2018/09/19 06:00 [medline] AID - S0733-8651(17)30156-X [pii] AID - 10.1016/j.ccl.2017.12.006 [doi] PST - ppublish SO - Cardiol Clin. 2018 May;36(2):241-256. doi: 10.1016/j.ccl.2017.12.006. PMID- 29669254 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20190329 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 48 IP - 4 DP - 2018 Apr 17 TI - Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. PG - 831-832 LID - S1074-7613(18)30133-X [pii] LID - 10.1016/j.immuni.2018.03.034 [doi] FAU - Kishore, Madhav AU - Kishore M FAU - Cheung, Kenneth C P AU - Cheung KCP FAU - Fu, Hongmei AU - Fu H FAU - Bonacina, Fabrizia AU - Bonacina F FAU - Wang, Guosu AU - Wang G FAU - Coe, David AU - Coe D FAU - Ward, Eleanor J AU - Ward EJ FAU - Colamatteo, Alessandra AU - Colamatteo A FAU - Jangani, Maryam AU - Jangani M FAU - Baragetti, Andrea AU - Baragetti A FAU - Matarese, Giuseppe AU - Matarese G FAU - Smith, David M AU - Smith DM FAU - Haas, Robert AU - Haas R FAU - Mauro, Claudio AU - Mauro C FAU - Wraith, David C AU - Wraith DC FAU - Okkenhaug, Klaus AU - Okkenhaug K FAU - Catapano, Alberico L AU - Catapano AL FAU - De Rosa, Veronica AU - De Rosa V FAU - Norata, Giuseppe D AU - Norata GD FAU - Marelli-Berg, Federica M AU - Marelli-Berg FM LA - eng GR - BBS/E/B/000C0407/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Published Erratum PL - United States TA - Immunity JT - Immunity JID - 9432918 EFR - Immunity. 2017 Nov 21;47(5):875-889.e10. PMID: 29166588 PMC - PMC5910171 EDAT- 2018/04/19 06:00 MHDA- 2018/04/19 06:01 CRDT- 2018/04/19 06:00 PHST- 2018/04/19 06:00 [entrez] PHST- 2018/04/19 06:00 [pubmed] PHST- 2018/04/19 06:01 [medline] AID - S1074-7613(18)30133-X [pii] AID - 10.1016/j.immuni.2018.03.034 [doi] PST - ppublish SO - Immunity. 2018 Apr 17;48(4):831-832. doi: 10.1016/j.immuni.2018.03.034. PMID- 29045644 OWN - NLM STAT- In-Data-Review LR - 20180410 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 14 DP - 2018 Apr 7 TI - 2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia. PG - 1131-1143 LID - 10.1093/eurheartj/ehx549 [doi] FAU - Landmesser, Ulf AU - Landmesser U AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin Institute of Health (BIH), German Center of Cardiovascular Research (DZHK), Hindenburgdamm 30, 12203 Berlin, Germany. FAU - Chapman, M John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), University of Pierre and Marie Curie, Pitie-Salpetriere Hospital, Paris, France. FAU - Stock, Jane K AU - Stock JK AD - European Atherosclerosis Society, Gothenburg, Sweden. FAU - Amarenco, Pierre AU - Amarenco P AD - Paris-Diderot-Sorbonne University and Department of Neurology and Stroke Centre, Bichat Hospital, Paris, France. FAU - Belch, Jill J F AU - Belch JJF AD - Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee, UK. FAU - Boren, Jan AU - Boren J AD - Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, and Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Farnier, Michel AU - Farnier M AD - Lipid Clinic, Point Medical, and Department of Cardiology, CHU Dijon-Bourgogne, Dijon, France. FAU - Ference, Brian A AU - Ference BA AD - Division of Cardiovascular Medicine, Division of Translational Research and Clinical Epidemiology, Wayne State University School of Medicine, Detroit, MI, USA. FAU - Gielen, Stephan AU - Gielen S AD - Department of Internal Medicine III, Martin-Luther-University Halle/Wittenberg, University Hospital, Halle/Saale, Germany. FAU - Graham, Ian AU - Graham I AD - Trinity College, Dublin, Ireland. FAU - Grobbee, Diederick E AU - Grobbee DE AD - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. FAU - Luscher, Thomas F AU - Luscher TF AD - University Heart Center, Department of Cardiology, University Hospital Zurich, and Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland. FAU - Piepoli, Massimo F AU - Piepoli MF AD - Heart Failure Unit, Cardiac Department, G Da Saliceto Hospital, Piacenza, Italy. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College, London, UK. FAU - Stroes, Erik S AU - Stroes ES AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. FAU - Wiklund, Olov AU - Wiklund O AD - Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Windecker, Stephan AU - Windecker S AD - Department of Cardiology, Swiss Cardiovascular Center Bern, Bern University Hospital, Bern, Switzerland. FAU - Zamorano, Jose Luis AU - Zamorano JL AD - Department of Cardiology, University Hospital Ramon y Cajal, Madrid, Spain. FAU - Pinto, Fausto AU - Pinto F AD - Cardiology Department, CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Portugal. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Department of Cardiology, Hacettepe University, Ankara, Turkey. FAU - Bax, Jeroen J AU - Bax JJ AD - Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and Multimedica IRCSS Milano, Italy. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 EDAT- 2017/10/19 06:00 MHDA- 2017/10/19 06:00 CRDT- 2017/10/19 06:00 PHST- 2017/06/24 00:00 [received] PHST- 2017/09/11 00:00 [accepted] PHST- 2017/10/19 06:00 [pubmed] PHST- 2017/10/19 06:00 [medline] PHST- 2017/10/19 06:00 [entrez] AID - 4554775 [pii] AID - 10.1093/eurheartj/ehx549 [doi] PST - ppublish SO - Eur Heart J. 2018 Apr 7;39(14):1131-1143. doi: 10.1093/eurheartj/ehx549. PMID- 29499359 OWN - NLM STAT- In-Process LR - 20190119 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 271 DP - 2018 Apr TI - Statin utilization and lipid goal attainment in high or very-high cardiovascular risk patients: Insights from Italian general practice. PG - 120-127 LID - S0021-9150(18)30087-X [pii] LID - 10.1016/j.atherosclerosis.2018.02.024 [doi] AB - BACKGROUND AND AIMS: Statin utilization and lipid goal achievement were estimated in a large sample of Italian patients at high/very-high cardiovascular (CV) risk. METHODS: Patients aged >/=18 years with a valid low-density lipoprotein cholesterol (LDL-C) measurement in 2015 were selected from the IMS Health Real World Data database; non-high-density lipoprotein cholesterol (non-HDL-C) was assessed in those with available total cholesterol measurements. Index dates were defined as the last valid lipid measurement in 2015. Patients were hierarchically classified into mutually exclusive risk categories: heterozygous familial hypercholesterolemia (primary and secondary prevention), atherosclerotic CV disease (including recent acute coronary syndrome [ACS], chronic coronary heart disease, stroke, and peripheral arterial disease), and diabetes mellitus (DM) alone. Statin and non-statin lipid-modifying therapy (LMT) use, and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline-recommended goal attainment, were assessed. RESULTS: Among 66,158 patients meeting selection criteria, the overall rate of LMT prescriptions was 53.3%, including 7.7% on high-intensity statin therapy. Statin use was highest for recent ACS and lowest for DM alone. LDL-C goal attainment was 16.0% for <1.8mmol/l and 45.0% for <2.5mmol/l; 24.3% reached non-HDL-C <2.6mmol/l and 52.2% were at <3.3mmol/l. Goal achievement was greatest with high-intensity statin use. CONCLUSIONS: Statin use in this cohort was consistent with previous reports in Italian patients at high/very-high CV risk, and low relative to statin use in other European countries. The low rate of ESC/EAS lipid goal attainment observed was consistent with outcomes of other European studies. CI - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Arca, Marcello AU - Arca M AD - Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. Electronic address: marcello.arca@uniroma1.it. FAU - Ansell, David AU - Ansell D AD - IMS Health, London, UK. FAU - Averna, Maurizio AU - Averna M AD - Department of Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Italy. FAU - Fanelli, Francesca AU - Fanelli F AD - Sanofi, Milan, Italy. FAU - Gorcyca, Katherine AU - Gorcyca K AD - Sanofi, Bridgewater, NJ, USA. FAU - Iorga, Serban R AU - Iorga SR AD - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. FAU - Maggioni, Aldo P AU - Maggioni AP AD - ANMCO Research Center, Florence, Italy. FAU - Paizis, Georges AU - Paizis G AD - Sanofi, Milan, Italy. FAU - Tomic, Radovan AU - Tomic R AD - Sanofi, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180217 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 OTO - NOTNLM OT - *Cardiovascular disease OT - *Low-density lipoprotein cholesterol OT - *Non-high-density lipoprotein cholesterol OT - *Prevention OT - *Statin EDAT- 2018/03/03 06:00 MHDA- 2018/03/03 06:00 CRDT- 2018/03/03 06:00 PHST- 2017/12/15 00:00 [received] PHST- 2018/02/04 00:00 [revised] PHST- 2018/02/14 00:00 [accepted] PHST- 2018/03/03 06:00 [pubmed] PHST- 2018/03/03 06:00 [medline] PHST- 2018/03/03 06:00 [entrez] AID - S0021-9150(18)30087-X [pii] AID - 10.1016/j.atherosclerosis.2018.02.024 [doi] PST - ppublish SO - Atherosclerosis. 2018 Apr;271:120-127. doi: 10.1016/j.atherosclerosis.2018.02.024. Epub 2018 Feb 17. PMID- 29507079 OWN - NLM STAT- MEDLINE DCOM- 20190212 LR - 20190401 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) VI - 19 IP - 4 DP - 2018 Apr TI - Zc3h10 is a novel mitochondrial regulator. LID - e45531 [pii] LID - 10.15252/embr.201745531 [doi] AB - Mitochondria are the energy-generating hubs of the cell. In spite of considerable advances, our understanding of the factors that regulate the molecular circuits that govern mitochondrial function remains incomplete. Using a genome-wide functional screen, we identify the poorly characterized protein Zinc finger CCCH-type containing 10 (Zc3h10) as regulator of mitochondrial physiology. We show that Zc3h10 is upregulated during physiological mitochondriogenesis as it occurs during the differentiation of myoblasts into myotubes. Zc3h10 overexpression boosts mitochondrial function and promotes myoblast differentiation, while the depletion of Zc3h10 results in impaired myoblast differentiation, mitochondrial dysfunction, reduced expression of electron transport chain (ETC) subunits, and blunted TCA cycle flux. Notably, we have identified a loss-of-function mutation of Zc3h10 in humans (Tyr105 to Cys105) that is associated with increased body mass index, fat mass, fasting glucose, and triglycerides. Isolated peripheral blood mononuclear cells from individuals homozygotic for Cys105 display reduced oxygen consumption rate, diminished expression of some ETC subunits, and decreased levels of some TCA cycle metabolites, which all together derive in mitochondrial dysfunction. Taken together, our study identifies Zc3h10 as a novel mitochondrial regulator. CI - (c) 2018 The Authors. FAU - Audano, Matteo AU - Audano M AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Pedretti, Silvia AU - Pedretti S AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Cermenati, Gaia AU - Cermenati G AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Brioschi, Elisabetta AU - Brioschi E AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Diaferia, Giuseppe Riccardo AU - Diaferia GR AD - Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy. FAU - Ghisletti, Serena AU - Ghisletti S AD - Humanitas Clinical and Research Center, Rozzano-Milan, Italy. FAU - Cuomo, Alessandro AU - Cuomo A AD - Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy. FAU - Bonaldi, Tiziana AU - Bonaldi T AD - Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy. FAU - Salerno, Franco AU - Salerno F AD - Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS C. Besta Neurological Institute, Milan, Italy. FAU - Mora, Marina AU - Mora M AD - Neuromuscular Diseases and Neuroimmunology Unit, Foundation IRCCS C. Besta Neurological Institute, Milan, Italy. FAU - Grigore, Liliana AU - Grigore L AD - IRCSS Multimedica, Milan, Italy. AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. AD - IRCSS Multimedica, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. AD - SISA Centre, Bassini Hospital, Cinisello Balsamo, Italy. AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Science, Curtin University, Perth, WA, Australia. FAU - Crestani, Maurizio AU - Crestani M AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Caruso, Donatella AU - Caruso D AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Saez, Enrique AU - Saez E AD - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. FAU - De Fabiani, Emma AU - De Fabiani E AUID- ORCID: 0000-0003-2406-1468 AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy emma.defabiani@unimi.it nico.mitro@unimi.it. FAU - Mitro, Nico AU - Mitro N AUID- ORCID: 0000-0002-5000-3619 AD - DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy emma.defabiani@unimi.it nico.mitro@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180305 PL - England TA - EMBO Rep JT - EMBO reports JID - 100963049 RN - 0 (Carrier Proteins) RN - 0 (Proteome) RN - 0 (ZC3H10 protein, human) SB - IM MH - Aged MH - Animals MH - Carrier Proteins/genetics/*metabolism MH - Cell Differentiation MH - Cell Line MH - Citric Acid Cycle MH - Computational Biology/methods MH - Energy Metabolism MH - Female MH - Gene Expression MH - Gene Expression Profiling MH - Gene Silencing MH - Humans MH - Male MH - Mice MH - Mitochondria/genetics/*metabolism MH - Muscle Fibers, Skeletal/metabolism MH - Muscle, Skeletal/metabolism MH - Mutation MH - Myoblasts/cytology/metabolism MH - Proteome MH - Proteomics/methods PMC - PMC5891430 OTO - NOTNLM OT - *Zc3h10 OT - *functional screens OT - *metabolism OT - *mitochondria EDAT- 2018/03/07 06:00 MHDA- 2019/02/13 06:00 CRDT- 2018/03/07 06:00 PHST- 2017/11/22 00:00 [received] PHST- 2018/02/02 00:00 [revised] PHST- 2018/02/07 00:00 [accepted] PHST- 2018/03/07 06:00 [pubmed] PHST- 2019/02/13 06:00 [medline] PHST- 2018/03/07 06:00 [entrez] AID - embr.201745531 [pii] AID - 10.15252/embr.201745531 [doi] PST - ppublish SO - EMBO Rep. 2018 Apr;19(4). pii: embr.201745531. doi: 10.15252/embr.201745531. Epub 2018 Mar 5. PMID- 29194462 OWN - NLM STAT- MEDLINE DCOM- 20190125 LR - 20190125 IS - 2055-6845 (Electronic) VI - 4 IP - 2 DP - 2018 Apr 1 TI - New strategies for the development of lipid-lowering therapies to reduce cardiovascular risk. PG - 119-127 LID - 10.1093/ehjcvp/pvx031 [doi] AB - The very high occurrence of cardiovascular events presents a major public health issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels. Opportunities for innovation in dyslipidaemia treatment should address the substantial risk of lipid-associated cardiovascular events among patients optimally treated per guidelines but who cannot achieve LDL-C goals and who could benefit from additional LDL-C-lowering therapy or experience side effects of statins. Fresh approaches are needed to identify promising drug targets early and develop them efficiently. The Cardiovascular Round Table of the European Society of Cardiology (ESC) convened a workshop to discuss new lipid-lowering strategies for cardiovascular risk reduction. Opportunities to improve treatment approaches and the efficient study of new therapies were explored. Circulating biomarkers may not be fully reliable proxy indicators of the relationship between treatment effect and clinical outcome. Mendelian randomization studies may better inform development strategies and refine treatment targets before Phase 3. Trials should match the drug to appropriate lipid and patient profile, and guidelines may move towards a precision-based approach to individual patient management. Stakeholder collaboration is needed to ensure continued innovation and better international coordination of both regulatory aspects and guidelines. It should be noted that risk may also be addressed through increased attention to other risk factors such as smoking, hypertension, overweight, and inactivity. FAU - Graham, Ian AU - Graham I AD - Trinity College, Adelaide Health Foundation, Tallaght Hospital, Dublin 24, Ireland. FAU - Shear, Chuck AU - Shear C AD - Global Product Development/Internal Medicine, Pfizer, Inc., 235 E. 42nd Street, New York, New York 10017, NY, USA. FAU - De Graeff, Pieter AU - De Graeff P AD - Dutch Medicines Evaluation Board (CBG-MEB), Graadt Van Roggenweg 500, 3531 AH Utrecht, The Netherlands. AD - Department of Pharmacy and Clinical Pharmacology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. FAU - Boulton, Caroline AU - Boulton C AD - Novartis Pharma AG, Asklepios 8, 4056 Basel, Switzerland. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences and Multimedica IRCCS, University of Milan, via Balzaretti 9, 20133 Milano, Italy. FAU - Stough, Wendy Gattis AU - Stough WG AD - Departments of Clinical Research and Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, 217 Main St., Buies Creek, NC 27506, USA. FAU - Carlsson, Stefan C AU - Carlsson SC AD - Cardiovascular Pharmacology, AstraZeneca, Pepparredsleden 1, SE-431 83 Molndal, Sweden. FAU - De Backer, Guy AU - De Backer G AD - Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, University Hospital, K3, 4th floor, De Pintelaan 185, B9000 Ghent, Belgium. FAU - Emmerich, Joseph AU - Emmerich J AD - Universite Paris-Descartes, Cochin-Hotel Dieu Hospital, French National Agency for Medicines and Health Products Safety, 143/147, Boulevard, Anatole France 93285, Saint-Denis, France. FAU - Greenfeder, Scott AU - Greenfeder S AD - Regulatory Affairs, Daiichi-Sankyo, 211 Mt. Airy Road, Basking Ridge, NJ 07920, USA. FAU - Kim, Albert M AU - Kim AM AD - Internal Medicine Research Unit, Pfizer, Inc., 1 Portland St., 4th floor, Cambridge, MA 02139, USA. FAU - Lautsch, Dominik AU - Lautsch D AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. FAU - Nguyen, Tu AU - Nguyen T AD - Sanofi, 55 Corporate Drive, Bridgewater, NJ, USA. FAU - Nissen, Steven E AU - Nissen SE AD - Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. FAU - Prasad, Krishna AU - Prasad K AD - Licensing Division, United Kingdom Medicines and Healthcare Products Regulatory Agency, 151 Buckingham Palace Road, London SW1W 9SZ, UK. FAU - Ray, Kausik K AU - Ray KK AD - Department of Primary Care and Public Health, Imperial College, 323 Reynolds Building, Room 320, Charing Cross Hospital, London W68RF, UK. FAU - Robinson, Jennifer G AU - Robinson JG AD - Department of Epidemiology, College of Public Health, University of Iowa, 145 N. Riverside Dr S455 CPHB, Iowa City, IA 52242, USA. FAU - Sasiela, William J AU - Sasiela WJ AD - Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. FAU - Bruins Slot, Karsten AU - Bruins Slot K AD - Oslo University Hospital, Ulleval, Medical Department, Postboks 4956 Nydalen, 0424 Oslo, Norway. FAU - Stroes, Erik AU - Stroes E AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. FAU - Thuren, Tom AU - Thuren T AD - Novartis Pharma AG, Asklepios 8, 4056 Basel, Switzerland. FAU - Van der Schueren, Bart AU - Van der Schueren B AD - Laboratory of Experimental Medicine and Endocrinology, University of Leuven, Herestraat 49, 3000 Leuven, Belgium. FAU - Velkovski-Rouyer, Maja AU - Velkovski-Rouyer M AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. FAU - Wasserman, Scott M AU - Wasserman SM AD - Amgen, One Amgen Center Drive, MS 38.2.C, Thousand Oaks, CA 91320, USA. FAU - Wiklund, Olov AU - Wiklund O AD - Wallenberg Laboratory, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden. FAU - Zouridakis, Emmanouil AU - Zouridakis E AD - Licensing Division, United Kingdom Medicines and Healthcare Products Regulatory Agency, 151 Buckingham Palace Road, London SW1W 9SZ, UK. CN - European Society of Cardiology Cardiovascular Roundtable LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Eur Heart J Cardiovasc Pharmacother JT - European heart journal. Cardiovascular pharmacotherapy JID - 101669491 RN - 0 (Hypolipidemic Agents) RN - 0 (Lipids) SB - IM MH - Cardiology/*standards MH - *Cardiovascular Diseases/blood/epidemiology/prevention & control MH - Drug Development/*standards MH - Global Health MH - Humans MH - Hypolipidemic Agents/*therapeutic use MH - Incidence MH - Lipids/*blood MH - *Practice Guidelines as Topic MH - Risk Factors IR - Clement-Baudena G FIR - Clement-Baudena, Ghislaine IR - Gropper S FIR - Gropper, Savion IR - Hamer A FIR - Hamer, Andrew IR - Molemans B FIR - Molemans, Bart IR - Sourdille T FIR - Sourdille, Timothee IR - Tahbaz A FIR - Tahbaz, Arash IR - Thorstensen C FIR - Thorstensen, Cathrine EDAT- 2017/12/02 06:00 MHDA- 2019/01/27 06:00 CRDT- 2017/12/02 06:00 PHST- 2017/06/13 00:00 [received] PHST- 2017/11/27 00:00 [accepted] PHST- 2017/12/02 06:00 [pubmed] PHST- 2019/01/27 06:00 [medline] PHST- 2017/12/02 06:00 [entrez] AID - 4670643 [pii] AID - 10.1093/ehjcvp/pvx031 [doi] PST - ppublish SO - Eur Heart J Cardiovasc Pharmacother. 2018 Apr 1;4(2):119-127. doi: 10.1093/ehjcvp/pvx031. PMID- 29428206 OWN - NLM STAT- MEDLINE DCOM- 20190118 LR - 20190118 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 130 DP - 2018 Apr TI - Proprotein Convertase Subtilisin-Kexin type-9 (PCSK9) and triglyceride-rich lipoprotein metabolism: Facts and gaps. PG - 1-11 LID - S1043-6618(17)31656-0 [pii] LID - 10.1016/j.phrs.2018.01.025 [doi] AB - After more than a decade of intense investigation, Pro-protein Convertase Subtilisin-Kexin type 9 (PCSK9) remains a hot topic of research both at experimental and clinical level. Interestingly PCSK9 is expressed in different tissues suggesting the existence of additional function(s) beyond the modulation of the Low-Density Lipoprotein (LDL) receptor in the liver. Emerging data suggest that PCSK9 might play a role in the modulation of triglyceride-rich lipoprotein (TGRL) metabolism, mainly Very Low-Density Lipoproteins (VLDL) and their remnants. In vitro, PCSK9 affects TGRLs production by intestinal cells as well as the catabolism of LDL receptor homologous and non-homologous targets such as VLDL receptor, CD36 and ApoE2R. However, the in vivo relevance of these findings is still debated. This review aims at critically discussing the role of PCSK9 on TGRLs metabolism with a major focus on the impact of its genetic and pharmacological modulation on circulating lipids and lipoproteins beyond LDL. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, via Balzaretti 9, 20133, Milan, Italy; S.I.S.A. Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Grejtakova, Daniela AU - Grejtakova D AD - IRCCS MultiMedica, via Fantoli 16, 20138, Milan, Italy. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti, 9, 20133 Milano, Italy. FAU - Olmastroni, Elena AU - Olmastroni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti, 9, 20133 Milano, Italy. FAU - Jotti, Gloria Saccani AU - Jotti GS AD - Department of Medicine & Surgery, Faculty of Medicine, University of Parma, Via Volturno 39, 43121 Parma, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, via Balzaretti 9, 20133, Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Kent St., Bentley Western Australia 6102, Australia. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica, via Fantoli 16, 20138, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Bellosta, Stefano AU - Bellosta S AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica, via Fantoli 16, 20138, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20180208 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Lipoproteins) RN - 0 (Receptors, LDL) RN - 0 (Triglycerides) RN - 0 (lipoprotein triglyceride) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM MH - Animals MH - Humans MH - Lipoproteins/*metabolism MH - Proprotein Convertase 9/genetics/*metabolism MH - Receptors, LDL/metabolism MH - Triglycerides/*metabolism OTO - NOTNLM OT - *Lipoproteins OT - *Metabolism OT - *Monoclonal antibodies OT - *PCSK9 OT - *Triglycerides EDAT- 2018/02/13 06:00 MHDA- 2019/01/19 06:00 CRDT- 2018/02/12 06:00 PHST- 2017/12/20 00:00 [received] PHST- 2018/01/24 00:00 [revised] PHST- 2018/01/26 00:00 [accepted] PHST- 2018/02/13 06:00 [pubmed] PHST- 2019/01/19 06:00 [medline] PHST- 2018/02/12 06:00 [entrez] AID - S1043-6618(17)31656-0 [pii] AID - 10.1016/j.phrs.2018.01.025 [doi] PST - ppublish SO - Pharmacol Res. 2018 Apr;130:1-11. doi: 10.1016/j.phrs.2018.01.025. Epub 2018 Feb 8. PMID- 29350058 OWN - NLM STAT- MEDLINE DCOM- 20190101 LR - 20190101 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 25 IP - 4 DP - 2018 Mar TI - The challenge of risk prediction: How good are we? PG - 418-419 LID - 10.1177/2047487317753893 [doi] FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - 1 Department of Cardiology, Hacettepe University, Ankara, Turkey. FAU - Catapano, Alberico L AU - Catapano AL AD - 2 Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy. AD - 3 Multimedica IRCCS, Italy. LA - eng PT - Editorial PT - Comment DEP - 20180119 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 97C5T2UQ7J (Cholesterol) SB - IM CON - Eur J Prev Cardiol. 2018 Mar;25(4):420-431. PMID: 29171772 MH - Cardiovascular Diseases MH - *Cholesterol MH - Humans MH - *Primary Prevention MH - Risk EDAT- 2018/01/20 06:00 MHDA- 2019/01/02 06:00 CRDT- 2018/01/20 06:00 PHST- 2018/01/20 06:00 [pubmed] PHST- 2019/01/02 06:00 [medline] PHST- 2018/01/20 06:00 [entrez] AID - 10.1177/2047487317753893 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2018 Mar;25(4):418-419. doi: 10.1177/2047487317753893. Epub 2018 Jan 19. PMID- 29445885 OWN - NLM STAT- MEDLINE DCOM- 20190213 LR - 20190215 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 20 IP - 3 DP - 2018 Feb 14 TI - The Interplay of Lipids, Lipoproteins, and Immunity in Atherosclerosis. PG - 12 LID - 10.1007/s11883-018-0715-0 [doi] AB - PURPOSE OF REVIEW: Atherosclerosis is an inflammatory disorder of the arterial wall, in which several players contribute to the onset and progression of the disease. Besides the well-established role of lipids, specifically cholesterol, and immune cell activation, new insights on the molecular mechanisms underlying the atherogenic process have emerged. RECENT FINDINGS: Meta-inflammation, a condition of low-grade immune response caused by metabolic dysregulation, immunological memory of innate immune cells (referred to as "trained immunity"), cholesterol homeostasis in dendritic cells, and immunometabolism, i.e., the interplay between immunological and metabolic processes, have all emerged as new actors during atherogenesis. These observations reinforced the interest in directly targeting inflammation to reduce cardiovascular disease. The novel acquisitions in pathophysiology of atherosclerosis reinforce the tight link between lipids, inflammation, and immune response, and support the benefit of targeting LDL-C as well as inflammation to decrease the CVD burden. How this will translate into the clinic will depend on the balance between costs (monoclonal antibodies either to PCSK9 or to IL-1ss), side effects (increased incidence of death due to infections for anti-IL-1ss antibody), and the benefits for patients at high CVD risk. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - IRCCS Multimedica, Milan, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS Multimedica, Milan, Italy. alberico.catapano@unimi.it. AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. alberico.catapano@unimi.it. AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti, 9, 20133, Milan, Italy. alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20180214 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - *Atherosclerosis/immunology/metabolism MH - Cardiovascular Diseases/prevention & control MH - *Cholesterol/immunology/metabolism MH - Humans MH - Immunity, Innate MH - Immunologic Memory MH - Inflammation/*metabolism MH - Metabolism/*immunology MH - Translational Medical Research OTO - NOTNLM OT - *Atherosclerosis OT - *Cholesterol OT - *Immune response OT - *Inflammation EDAT- 2018/02/16 06:00 MHDA- 2019/02/14 06:00 CRDT- 2018/02/16 06:00 PHST- 2018/02/16 06:00 [entrez] PHST- 2018/02/16 06:00 [pubmed] PHST- 2019/02/14 06:00 [medline] AID - 10.1007/s11883-018-0715-0 [doi] AID - 10.1007/s11883-018-0715-0 [pii] PST - epublish SO - Curr Atheroscler Rep. 2018 Feb 14;20(3):12. doi: 10.1007/s11883-018-0715-0. PMID- 29249427 OWN - NLM STAT- MEDLINE DCOM- 20180730 LR - 20180730 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 252 DP - 2018 Feb 1 TI - Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey. PG - 193-198 LID - S0167-5273(17)31308-6 [pii] LID - 10.1016/j.ijcard.2017.10.105 [doi] AB - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C) predisposing to premature cardiovascular disease. Its prevalence varies and has been estimated around 1 in 200-500. The Heredity survey evaluated the prevalence of potential FH and the therapeutic approaches among patients with established coronary artery disease (CAD) or peripheral artery disease (PAD) in which it is less well documented. METHODS: Data were collected in patients admitted to programs of rehabilitation and secondary prevention in Italy. Potential FH was estimated using Dutch Lipid Clinic Network (DLCN) criteria. Potential FH was defined as having a total score>/=6. RESULTS: Among the 1438 consecutive patients evaluated, the prevalence of potential FH was 3.7%. The prevalence was inversely related to age, with a putative prevalence of 1:10 in those with <55yrs of age (male) and <60yrs (female). Definite FH (DLCN score>8) had the highest percentages of patients after an ACS (75% vs 52.5% in the whole study population). At discharge, most patients were on high intensity statin therapy, but despite this, potential FH group still had a higher percentage of patients with LDL-C levels not at target and having a distance from the target higher than 50%. CONCLUSIONS: Among patients with established coronary heart disease, the prevalence of potential FH is higher than in the general population; the results suggest that a correct identification of potential FH, especially in younger patients, may help to better manage their high cardiovascular risk. CI - Copyright (c) 2017 Elsevier Ireland Ltd. All rights reserved. FAU - Faggiano, Pompilio AU - Faggiano P AD - Cardiologia Spedali Civili Brescia, Italy. Electronic address: iliofaggiano@alice.it. FAU - Pirillo, Angela AU - Pirillo A AD - Centro per lo Studio dell'Aterosclerosi, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Griffo, Raffaele AU - Griffo R AD - Cardiologist, Genova, Italy. FAU - Ambrosetti, Marco AU - Ambrosetti M AD - U.O. Cardiologia e Angiologia Riabilitativa, Clinica Le Terrazze, Cunardo, VA, Italy. FAU - Pedretti, Roberto AU - Pedretti R AD - Istituto Clinico Scientifico Maugeri, Pavia, Italy. FAU - Scorcu, Giampaolo AU - Scorcu G AD - SSD valutazione e consulenza cardiologica AO Brotzu, Cagliari, Italy. FAU - Werren, Marika AU - Werren M AD - U.O. Cardiologia Riabilitativa - IMFR Gervasutta, Udine, Italy. FAU - Febo, Oreste AU - Febo O AD - U.O. Cardiologia Riabilitativa, Rivolta D'Adda, Italy. FAU - Malfatto, Gabriella AU - Malfatto G AD - Istituto Auxologico Italiano, Milano, Italy. FAU - Favretto, Giuseppe AU - Favretto G AD - Cardiologia Riabilitativa Alta Specializzazione Motta di Livenza. Italy. FAU - Sarullo, Filippo AU - Sarullo F AD - Ospedale Buccheri La Ferla Fatebenefratelli Palermo, Italy. FAU - Antonini-Canterin, Francesco AU - Antonini-Canterin F AD - Ospedale di Sacile, Pordenone, Italy. FAU - Zobbi, Gianni AU - Zobbi G AD - Centro Riabilitazione Cardiologica Ospedale S.Anna Castelnovo ne Monti, Reggio Emilia, Italy. FAU - Temporelli, Pierluigi AU - Temporelli P AD - Istituto Clinico Scientifico Maugeri, Veruno, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Dipartimento Scienze Farmacologiche e Biomolecolari and IRCCS Multimedica Milano, Italy. CN - Centro Studi e Formazione - Italian Association for Cardiovascular Prevention and Rehabilitation LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Anticholesteremic Agents) SB - IM CIN - Int J Cardiol. 2018 Feb 1;252:199-200. PMID: 29249428 MH - Aged MH - Anticholesteremic Agents/therapeutic use MH - Coronary Artery Disease/blood/*epidemiology/*therapy MH - *Disease Management MH - Female MH - Heredity MH - Humans MH - Hyperlipoproteinemia Type II/blood/*epidemiology/*therapy MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Prevalence MH - Retrospective Studies MH - *Surveys and Questionnaires OTO - NOTNLM OT - Coronary artery disease OT - Familial hypercholesterolemia OT - Lower extremities peripheral disease OT - Prevalence OT - Statins EDAT- 2017/12/19 06:00 MHDA- 2018/07/31 06:00 CRDT- 2017/12/19 06:00 PHST- 2017/10/25 00:00 [revised] PHST- 2017/10/26 00:00 [accepted] PHST- 2017/12/19 06:00 [entrez] PHST- 2017/12/19 06:00 [pubmed] PHST- 2018/07/31 06:00 [medline] AID - S0167-5273(17)31308-6 [pii] AID - 10.1016/j.ijcard.2017.10.105 [doi] PST - ppublish SO - Int J Cardiol. 2018 Feb 1;252:193-198. doi: 10.1016/j.ijcard.2017.10.105. PMID- 29336436 OWN - NLM STAT- In-Data-Review LR - 20181113 IS - 1759-5010 (Electronic) IS - 1759-5002 (Linking) VI - 15 IP - 2 DP - 2018 Jan 16 TI - Dyslipidaemias in 2017: Atherogenic lipoproteins as treatment targets. PG - 75-76 LID - 10.1038/nrcardio.2017.221 [doi] FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy; and IRCCS MultiMedica, Sesto S. Giovanni, Via Milanese 100, 20099 Milan, Italy. LA - eng PT - Journal Article PL - England TA - Nat Rev Cardiol JT - Nature reviews. Cardiology JID - 101500075 EDAT- 2018/01/18 06:00 MHDA- 2018/01/18 06:00 CRDT- 2018/01/17 06:00 PHST- 2018/01/17 06:00 [entrez] PHST- 2018/01/18 06:00 [pubmed] PHST- 2018/01/18 06:00 [medline] AID - nrcardio.2017.221 [pii] AID - 10.1038/nrcardio.2017.221 [doi] PST - ppublish SO - Nat Rev Cardiol. 2018 Jan 16;15(2):75-76. doi: 10.1038/nrcardio.2017.221. PMID- 28958460 OWN - NLM STAT- MEDLINE DCOM- 20181011 LR - 20181011 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 47 DP - 2018 Jan TI - Good adherence to therapy with statins reduces the risk of adverse clinical outcomes even among very elderly. Evidence from an Italian real-life investigation. PG - 25-31 LID - S0953-6205(17)30372-2 [pii] LID - 10.1016/j.ejim.2017.09.023 [doi] AB - AIM: To assess whether in individuals aged 80years or older adherence to statins is accompanied by a reduced risk of all-cause mortality and major cardiovascular events. METHODS: A nested case-control study was carried out on a cohort of patients aged 80years or older (very elderly individuals), who were under treatment with statins between 2008 and 2009, using the database available for all citizenship (about 10 million) of Lombardy (Italy). Cases were the cohort members who experienced death or hospitalization for stroke, myocardial infarction or heart failure from the initial prescription until 2012. Up to five controls were randomly selected for each case. Logistic regression was used to model the outcome risk associated with the adherence to therapy with statins. Two younger patient cohorts aged 60 to 69years and 70 to 79years were taken for comparison. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. RESULTS: Among very elderly individuals, those who had high adherence to statins showed significant risk reductions of death (56%; 95% Confidence Interval, 54% to 59%), myocardial infarction (15%; 5% to 24%), stroke (13%; 0% to 24%) and heart failure (30%; 23% to 36%) with respect to those at very low adherence. Adherence-related risk reductions were only slightly better for younger cohort members. CONCLUSIONS: Adherence to therapy with statins reduced the risk of both death and cardiovascular morbidity in patients aged 80years or older. CI - Copyright (c) 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Corrao, Giovanni AU - Corrao G AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. FAU - Monzio Compagnoni, Matteo AU - Monzio Compagnoni M AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Franchi, Matteo AU - Franchi M AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Cantarutti, Anna AU - Cantarutti A AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Pugni, Pietro AU - Pugni P AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Lombardy Region, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy; IRCSS Multimedica, Sesto San Giovanni, Milan, Italy. FAU - Mancia, Giuseppe AU - Mancia G AD - University of Milano-Bicocca, Milan, Italy. LA - eng PT - Comparative Study PT - Journal Article DEP - 20170927 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Aged MH - Aged, 80 and over MH - Case-Control Studies MH - Cohort Studies MH - Female MH - Heart Failure/mortality/*prevention & control MH - Hospitalization/statistics & numerical data MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypercholesterolemia/complications/*drug therapy MH - Italy/epidemiology MH - Logistic Models MH - Male MH - *Medication Adherence MH - Middle Aged MH - Myocardial Infarction/mortality/*prevention & control MH - Risk Reduction Behavior MH - Stroke/mortality/*prevention & control OTO - NOTNLM OT - *Adherence OT - *Cardiovascular outcomes OT - *Elderly OT - *Healthcare utilization database OT - *Mortality OT - *Record linkage OT - *Statins OT - *Very elderly EDAT- 2017/09/30 06:00 MHDA- 2018/10/12 06:00 CRDT- 2017/09/30 06:00 PHST- 2017/04/19 00:00 [received] PHST- 2017/08/31 00:00 [revised] PHST- 2017/09/21 00:00 [accepted] PHST- 2017/09/30 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2017/09/30 06:00 [entrez] AID - S0953-6205(17)30372-2 [pii] AID - 10.1016/j.ejim.2017.09.023 [doi] PST - ppublish SO - Eur J Intern Med. 2018 Jan;47:25-31. doi: 10.1016/j.ejim.2017.09.023. Epub 2017 Sep 27. PMID- 29150407 OWN - NLM STAT- MEDLINE DCOM- 20190314 LR - 20190314 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 28 IP - 1 DP - 2018 Jan TI - Disease trends over time and CD4(+)CCR5(+) T-cells expansion predict carotid atherosclerosis development in patients with systemic lupus erythematosus. PG - 53-63 LID - S0939-4753(17)30202-8 [pii] LID - 10.1016/j.numecd.2017.09.001 [doi] AB - BACKGROUND AND AIM: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study. METHODS AND RESULTS: Clinical history and information on principal CVRFs were collected at baseline and after 5 years in 40 SLE patients (36 women, mean age 42 +/- 9 years; 14.4 +/- 7 years of mean disease duration) and 50 age-matched controls. Carotid Doppler ultrasonography was employed to quantify the atherosclerotic burden at baseline and at follow up. Clinimetrics were applied to assess SLE activity over time (SLEDAI). The association between basal circulating T cell subsets (including CD4(+)CCR5(+); CD4(+)CXCR3(+); CD4(+)HLADR(+); CD4(+)CD45RA(+)RO(-), CD4(+)CD45RO(+)RA(-) and their subsets) and atherosclerosis development was evaluated. During the 5-year follow up, 32% of SLE patients, developed carotid atherosclerosis compared to 4% of controls. Furthermore, considering SLEDAI changes over time, patients within the highest tertile were those with increased incidence of carotid atherosclerosis independently of CVRF. In addition, increased levels of CD4(+)CCR5(+) T cells were independently associated with the development of carotid atherosclerosis in SLE patients. CONCLUSION: Serial clinical evaluations over time, rather than a single point estimation of disease activity or CVRF burden, are required to define the risk of carotid atherosclerosis development in SLE patients. Specific T cell subsets are associated with long-term atherosclerotic progression and may further be of help in predicting vascular disease progression. CI - Copyright (c) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Baragetti, A AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy. FAU - Ramirez, G A AU - Ramirez GA AD - Universita Vita-Salute San Raffaele, Milan, Italy; Unit of Medicine and Clinical Immunology, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Magnoni, M AU - Magnoni M AD - Department of Thoracic and Cardiovascular Surgery, Universita Vita-Salute San Raffaele Scientific Institute Milan, Italy. FAU - Garlaschelli, K AU - Garlaschelli K AD - Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy. FAU - Grigore, L AU - Grigore L AD - Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy; IRCCS - Multimedica Hospital, Sesto San Giovanni, Italy. FAU - Berteotti, M AU - Berteotti M AD - Department of Thoracic and Cardiovascular Surgery, Universita Vita-Salute San Raffaele Scientific Institute Milan, Italy. FAU - Scotti, I AU - Scotti I AD - Department of Thoracic and Cardiovascular Surgery, Universita Vita-Salute San Raffaele Scientific Institute Milan, Italy. FAU - Bozzolo, E AU - Bozzolo E AD - Universita Vita-Salute San Raffaele, Milan, Italy. FAU - Berti, A AU - Berti A AD - Universita Vita-Salute San Raffaele, Milan, Italy; Unit of Medicine and Clinical Immunology, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Camici, P G AU - Camici PG AD - Department of Thoracic and Cardiovascular Surgery, Universita Vita-Salute San Raffaele Scientific Institute Milan, Italy. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; IRCCS - Multimedica Hospital, Sesto San Giovanni, Italy. FAU - Manfredi, A A AU - Manfredi AA AD - Universita Vita-Salute San Raffaele, Milan, Italy; Unit of Medicine and Clinical Immunology, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Ammirati, E AU - Ammirati E AD - Niguarda Ca' Granda Hospital, Milan, Italy. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Science, Curtin University, Perth, Western Australia, Australia. Electronic address: danilo.norata@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170918 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Biomarkers) RN - 0 (CCR5 protein, human) RN - 0 (Receptors, CCR5) SB - IM MH - Adult MH - Biomarkers/blood MH - CD4-Positive T-Lymphocytes/*immunology/metabolism MH - Carotid Artery Diseases/blood/diagnosis/*immunology MH - *Cell Proliferation MH - Disease Progression MH - Female MH - Humans MH - Longitudinal Studies MH - Lupus Erythematosus, Systemic/blood/complications/diagnosis/*immunology MH - Lymphocyte Count MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Prospective Studies MH - Receptors, CCR5/blood/*immunology MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Ultrasonography, Doppler OTO - NOTNLM OT - *Adaptive immunity OT - *Carotid atherosclerosis OT - *Systemic lupus erythematosus EDAT- 2017/11/19 06:00 MHDA- 2019/03/15 06:00 CRDT- 2017/11/19 06:00 PHST- 2017/02/09 00:00 [received] PHST- 2017/09/07 00:00 [revised] PHST- 2017/09/09 00:00 [accepted] PHST- 2017/11/19 06:00 [pubmed] PHST- 2019/03/15 06:00 [medline] PHST- 2017/11/19 06:00 [entrez] AID - S0939-4753(17)30202-8 [pii] AID - 10.1016/j.numecd.2017.09.001 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2018 Jan;28(1):53-63. doi: 10.1016/j.numecd.2017.09.001. Epub 2017 Sep 18. PMID- 28914630 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20180611 IS - 1473-6535 (Electronic) IS - 0957-9672 (Linking) VI - 28 IP - 6 DP - 2017 Dec TI - Strategies for the use of nonstatin therapies. PG - 458-464 LID - 10.1097/MOL.0000000000000459 [doi] AB - PURPOSE OF REVIEW: Dyslipidaemias are a major risk factor for cardiovascular disease (CVD); in particular, high levels of low-density lipoprotein cholesterol (LDL-C) have been associated to a higher cardiovascular risk. Reducing LDL-C levels decreases the risk of coronary heart disease (CHD), and the greater the LDL-C reduction, the greater the decrease in cardiovascular risk. Although statins represent the first line lipid-lowering therapy, many patients do not reach the recommended goals or exhibit adverse side effects leading to therapy discontinuation; in addition, a significant percentage of statin-treated patients continue to experience cardiovascular events even in the presence of well controlled LDL-C levels, because of alterations in other lipid/lipoprotein classes, including triglycerides and high-density lipoprotein cholesterol. RECENT FINDINGS: These conditions require further therapeutic interventions to achieve the recommended lipid goals. Several drugs have been developed to address these needs. Recent studies have shown that the association of ezetimibe with rosuvastatin or atorvastatin results in a better hypolipidaemic effect; in addition to this, PCSK9 inhibitors significantly reduce LDL-C levels and cardiovascular events. SUMMARY: For patients who are intolerant to statins or not able to reach the recommended LDL-C levels, despite maximal tolerated dose of statin, or exhibiting additional lipid alterations, several drugs are available that can be used either in monotherapy or on top of the maximally tolerated dose of statins. FAU - Pirillo, Angela AU - Pirillo A AD - aCenter for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo bIRCCS Multimedica Hospital, Sesto San Giovanni cDepartment of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy dSchool of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia. FAU - Norata, Giuseppe D AU - Norata GD FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - England TA - Curr Opin Lipidol JT - Current opinion in lipidology JID - 9010000 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipids) SB - IM MH - Drug Discovery MH - Dyslipidemias/blood/*drug therapy MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/therapeutic use MH - Lipids/blood EDAT- 2017/09/16 06:00 MHDA- 2018/06/12 06:00 CRDT- 2017/09/16 06:00 PHST- 2017/09/16 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] PHST- 2017/09/16 06:00 [entrez] AID - 10.1097/MOL.0000000000000459 [doi] PST - ppublish SO - Curr Opin Lipidol. 2017 Dec;28(6):458-464. doi: 10.1097/MOL.0000000000000459. PMID- 29166588 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20181113 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 47 IP - 5 DP - 2017 Nov 21 TI - Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. PG - 875-889.e10 LID - S1074-7613(17)30472-7 [pii] LID - 10.1016/j.immuni.2017.10.017 [doi] AB - Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration. CI - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Kishore, Madhav AU - Kishore M AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Cheung, Kenneth C P AU - Cheung KCP AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Fu, Hongmei AU - Fu H AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy. FAU - Wang, Guosu AU - Wang G AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Coe, David AU - Coe D AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Ward, Eleanor J AU - Ward EJ AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Colamatteo, Alessandra AU - Colamatteo A AD - Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Naples 80131, Italy. FAU - Jangani, Maryam AU - Jangani M AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy. FAU - Matarese, Giuseppe AU - Matarese G AD - Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Naples 80131, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita di Napoli "Federico II," Naples 80131, Italy. FAU - Smith, David M AU - Smith DM AD - Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, Cambridgeshire CB40WG, UK. FAU - Haas, Robert AU - Haas R AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Mauro, Claudio AU - Mauro C AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. FAU - Wraith, David C AU - Wraith DC AD - Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK. FAU - Okkenhaug, Klaus AU - Okkenhaug K AD - Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy; IRCCS Multimedica Hospital, Milan 20138, Italy. FAU - De Rosa, Veronica AU - De Rosa V AD - Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Naples 80131, Italy. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia. FAU - Marelli-Berg, Federica M AU - Marelli-Berg FM AD - William Harvey Research Institute, Queen Mary University of London, London EC1M6BQ, UK. Electronic address: f.marelli-berg@qmul.ac.uk. LA - eng GR - RG/14/2/30616/British Heart Foundation/United Kingdom GR - FS/12/38/29640/British Heart Foundation/United Kingdom GR - BBS/E/B/000C0409/Biotechnology and Biological Sciences Research Council/United Kingdom GR - CH/15/2/32064 /British Heart Foundation/United Kingdom GR - BBS/E/B/000C0407/Biotechnology and Biological Sciences Research Council/United Kingdom GR - FS/11/64/28945/British Heart Foundation/United Kingdom GR - PG/15/105/31906/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CD28 Antigens) RN - 0 (CTLA-4 Antigen) RN - 0 (GCKR protein, human) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.2 (Glucokinase) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM EIN - Immunity. 2018 Apr 17;48(4):831-832. PMID: 29669254 MH - Adaptor Proteins, Signal Transducing/genetics MH - Animals MH - CD28 Antigens/physiology MH - CTLA-4 Antigen/physiology MH - Cells, Cultured MH - Glucokinase/*physiology MH - *Glycolysis MH - Humans MH - Mechanistic Target of Rapamycin Complex 1/physiology MH - Mechanistic Target of Rapamycin Complex 2/physiology MH - Mice MH - Mice, Inbred Strains MH - Phosphatidylinositol 3-Kinases/physiology MH - Proto-Oncogene Proteins c-akt/physiology MH - T-Lymphocytes, Regulatory/*physiology PMC - PMC5714502 OTO - NOTNLM OT - *CD28 OT - *CTLA-4 OT - *glycolysis OT - *mTOR OT - *metabolism OT - *migration OT - *regulatory T cells EDAT- 2017/11/23 06:00 MHDA- 2017/12/06 06:00 CRDT- 2017/11/23 06:00 PHST- 2016/12/22 00:00 [received] PHST- 2017/06/30 00:00 [revised] PHST- 2017/10/26 00:00 [accepted] PHST- 2017/11/23 06:00 [entrez] PHST- 2017/11/23 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] AID - S1074-7613(17)30472-7 [pii] AID - 10.1016/j.immuni.2017.10.017 [doi] PST - ppublish SO - Immunity. 2017 Nov 21;47(5):875-889.e10. doi: 10.1016/j.immuni.2017.10.017. PMID- 28877913 OWN - NLM STAT- MEDLINE DCOM- 20171127 LR - 20171128 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 136 IP - 20 DP - 2017 Nov 14 TI - Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up. PG - 1878-1891 LID - 10.1161/CIRCULATIONAHA.117.027966 [doi] AB - BACKGROUND: Patients with primary elevations of low-density lipoprotein cholesterol (LDL-C) >/=190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomized trial evidence supporting these recommendations in primary prevention. In the present analysis, we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C >/=190 mg/dL. METHODS: We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C >/=190 mg/dL without preexisting vascular disease at baseline. We performed post hoc analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) randomized, placebo-controlled trial, and observational posttrial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45 to 64 years, who were randomly assigned to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C <190 mg/dL (n=2969; mean LDL-C 178+/-6 mg/dL) and those with LDL-C >/=190 mg/dL (n=2560; mean LDL-C 206+/-12 mg/dL). The effect of pravastatin versus placebo on coronary heart disease and major adverse cardiovascular events were assessed over the 4.9-year randomized controlled trial phase and on mortality outcomes over a total of 20 years of follow-up. RESULTS: Among 5529 individuals without vascular disease, pravastatin reduced the risk of coronary heart disease by 27% (P=0.002) and major adverse cardiovascular events by 25% (P=0.004) consistently among those with and without LDL-C >/=190 mg/dL (P-interaction >0.9). Among individuals with LDL-C >/=190 mg/dL, pravastatin reduced the risk of coronary heart disease by 27% (P=0.033) and major adverse cardiovascular events by 25% (P=0.037) during the initial trial phase and the risk of coronary heart disease death, cardiovascular death, and all-cause mortality by 28% (P=0.020), 25% (P=0.009), and 18% (P=0.004), respectively, over a total of 20 years of follow-up. CONCLUSIONS: The present analyses provide robust novel evidence for the short- and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C >/=190 mg/dL. CI - (c) 2017 American Heart Association, Inc. FAU - Vallejo-Vaz, Antonio J AU - Vallejo-Vaz AJ AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, United Kingdom (A.J.V.-V., K.K.R.). FAU - Robertson, Michele AU - Robertson M AD - Robertson Centre for Biostatistics, University of Glasgow, United Kingdom (M.R., I.F.). FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano and IRCCS Multimedica, Italy (A.L.C.). FAU - Watts, Gerald F AU - Watts GF AD - Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia (G.F.W.). FAU - Kastelein, John J AU - Kastelein JJ AD - Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands (J.J.K.). FAU - Packard, Chris J AU - Packard CJ AD - College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom (C.J.P.). FAU - Ford, Ian AU - Ford I AD - Robertson Centre for Biostatistics, University of Glasgow, United Kingdom (M.R., I.F.). FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, United Kingdom (A.J.V.-V., K.K.R.). k.ray@imperial.ac.uk. LA - eng PT - Journal Article PT - Observational Study PT - Randomized Controlled Trial DEP - 20170906 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - KXO2KT9N0G (Pravastatin) SB - AIM SB - IM CIN - BMJ. 2017 Oct 31;359:j4906. PMID: 29089361 CIN - BMJ. 2017 Oct 31;359:j4915. PMID: 29089296 CIN - Circulation. 2017 Nov 14;136(20):1892-1894. PMID: 29133529 MH - Anticholesteremic Agents/pharmacology/therapeutic use MH - Cardiovascular Diseases/*blood/epidemiology/*prevention & control MH - Cholesterol, LDL/antagonists & inhibitors/*blood MH - Coronary Disease/blood/drug therapy/epidemiology MH - Follow-Up Studies MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/*therapeutic use MH - Hypercholesterolemia/blood/drug therapy/epidemiology MH - Male MH - Middle Aged MH - Pravastatin/pharmacology/*therapeutic use MH - Primary Prevention/*methods/trends MH - Scotland/epidemiology OTO - NOTNLM OT - cardiovascular diseases OT - lipids OT - lipoproteins OT - primary prevention OT - statin therapy EDAT- 2017/09/08 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/09/08 06:00 PHST- 2017/02/18 00:00 [received] PHST- 2017/07/21 00:00 [accepted] PHST- 2017/09/08 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/09/08 06:00 [entrez] AID - CIRCULATIONAHA.117.027966 [pii] AID - 10.1161/CIRCULATIONAHA.117.027966 [doi] PST - ppublish SO - Circulation. 2017 Nov 14;136(20):1878-1891. doi: 10.1161/CIRCULATIONAHA.117.027966. Epub 2017 Sep 6. PMID- 28369752 OWN - NLM STAT- MEDLINE DCOM- 20180628 LR - 20181113 IS - 1476-5381 (Electronic) IS - 0007-1188 (Linking) VI - 174 IP - 22 DP - 2017 Nov TI - Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials. PG - 3973-3985 LID - 10.1111/bph.13805 [doi] AB - For long time, the role of LDL and inflammation in the pathogenesis of atherosclerosis have been studied independently from each other and only more recently a common platform has been suggested. Accumulation of excess cholesterol due to the presence of increased circulating LDL promotes endothelium dysfunction and activation, which is associated with increased production of pro-inflammatory cytokines, overexpression of adhesion molecules, chemokines and C-reactive protein (CRP), increased generation of reactive oxygen species and reduction of nitric oxide levels and bioavailability. All these processes favour the progressive infiltration of inflammatory cells within the arterial wall where cholesterol accumulates, both extracellularly and intracellularly, and promotes vascular inflammation. According to this, lipid-lowering therapies should improve inflammation and, indeed, statins decrease circulating inflammatory markers such as CRP and improve endothelial function and plaque burden. Pleiotropic activities have been proposed to explain this effect. However, mendelian randomization studies ruled out a direct role for CRP on coronary artery disease and studies with other lipid lowering drugs, such as ezetimibe showed that the beneficial effect of LDL-cholesterol-lowering therapies on systemic inflammatory status, as monitored by changes in CRP plasma levels, could be achieved, independently of the mechanism of action, only in patients presenting with baseline inflamed conditions. These observations strengthen the direct link between cholesterol and inflammation and indicate that decreasing LDL levels is one of the key goals for improving cardiovascular outcome. LINKED ARTICLES: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc. CI - (c) 2017 The British Pharmacological Society. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - IRCCS Multimedica Hospital, Sesto San Giovanni, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western, Australia. LA - eng PT - Journal Article PT - Review DEP - 20170505 PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Hypolipidemic Agents) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cardiovascular Diseases/*metabolism/prevention & control MH - Cholesterol/*metabolism MH - Humans MH - Hypercholesterolemia/drug therapy/metabolism MH - Hypolipidemic Agents/therapeutic use MH - Inflammation/drug therapy/*metabolism PMC - PMC5659993 EDAT- 2017/04/04 06:00 MHDA- 2018/06/29 06:00 CRDT- 2017/04/04 06:00 PHST- 2016/12/19 00:00 [received] PHST- 2017/02/24 00:00 [revised] PHST- 2017/03/13 00:00 [accepted] PHST- 2017/04/04 06:00 [pubmed] PHST- 2018/06/29 06:00 [medline] PHST- 2017/04/04 06:00 [entrez] AID - 10.1111/bph.13805 [doi] PST - ppublish SO - Br J Pharmacol. 2017 Nov;174(22):3973-3985. doi: 10.1111/bph.13805. Epub 2017 May 5. PMID- 29016810 OWN - NLM STAT- MEDLINE DCOM- 20180720 LR - 20180720 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 113 IP - 13 DP - 2017 Nov 1 TI - miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways. PG - 1627-1638 LID - 10.1093/cvr/cvx157 [doi] AB - Aims: Atherosclerosis is an inflammatory disease wherein cholesterol-loaded macrophages play a major role. MicroRNAs and microparticles propagate inflammatory pathways and are involved in cardiovascular disease. We aimed to screen and validate circulating microRNAs correlated with atherosclerosis development in humans, and to dissect the molecular mechanisms associated with atherogenesis using in vitro and in vivo approaches. Methods and results: A panel of 179 secreted microRNAs was screened in plasma samples of patients with and without atherosclerosis, and validated cross-sectionally and prospectively in patients followed for up to 11 years. miR-30c-5p was inversely correlated with total and LDL cholesterol, carotid intimal media thickness (CIMT), presence and future development of plaques. Using a human macrophage line and in vitro gene silencing strategies, we found that miR-30c-5p was downregulated by oxidized LDL (oxLDL) via the scavenger receptor CD36 and inhibition miR processing by Dicer. In turn, miR-30c-5p downregulation was responsible for the effects of oxLDL on macrophage IL-1beta release, caspase-3 expression, and apoptosis. miR-30c-5p loaded into microparticles was uptaken by macrophages and regulated target genes, like caspase-3, at transcriptional level. To establish the relevance of this pathway on endothelial damage as the earliest step of atherogenesis, we show that systemic miR-30c-5p knockdown induced caspase-3 and impaired endothelial healing after carotid injury in C57Bl/6 J mice. Conclusions: With an unbiased screening of secreted microRNAs, we identify reduction of miR-30c-5p in microparticles as a promoter of early atherosclerosis, by conveying pro-inflammatory pro-apoptotic signals and impairing endothelial healing. Therefore, stimulation of miR-30c-5p is a candidate direct anti-atherosclerotic therapy. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author 2017. For Permissions, please email: journals.permissions@oup.com. FAU - Ceolotto, Giulio AU - Ceolotto G AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. FAU - Giannella, Alessandra AU - Giannella A AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. FAU - Albiero, Mattia AU - Albiero M AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. AD - Venetian Institute of Molecular Medicine, 35128 Padova, Italy. FAU - Kuppusamy, Maniselvan AU - Kuppusamy M AD - Department of Medicine-Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Radu, Claudia AU - Radu C AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. FAU - Simioni, Paolo AU - Simioni P AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Iori, Elisabetta AU - Iori E AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. AD - Venetian Institute of Molecular Medicine, 35128 Padova, Italy. FAU - Avogaro, Angelo AU - Avogaro A AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. FAU - Vigili de Kreutzenberg, Saula AU - Vigili de Kreutzenberg S AD - Department of Medicine, DIMED, University of Padova, via Giustiniani, 2, 35128 Padova, Italy. LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (CD36 Antigens) RN - 0 (Cholesterol, LDL) RN - 0 (Circulating MicroRNA) RN - 0 (IL1B protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Lipoproteins, LDL) RN - 0 (MIRN30 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Mirn30d microRNA, mouse) RN - 0 (oxidized low density lipoprotein) RN - EC 3.1.26.3 (DICER1 protein, human) RN - EC 3.1.26.3 (Ribonuclease III) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM CIN - Cardiovasc Res. 2017 Nov 1;113(13):1536-1537. PMID: 29036285 MH - Animals MH - Apoptosis MH - CD36 Antigens/metabolism MH - Carotid Artery Diseases/diagnostic imaging/genetics/*metabolism/pathology MH - Carotid Artery Injuries/genetics/metabolism/pathology MH - Carotid Intima-Media Thickness MH - Case-Control Studies MH - Caspase 3/metabolism MH - Cholesterol, LDL/blood MH - Circulating MicroRNA/blood/genetics/*metabolism MH - Cross-Sectional Studies MH - DEAD-box RNA Helicases/metabolism MH - Disease Models, Animal MH - Endothelial Cells/metabolism/pathology MH - Humans MH - Inflammation/genetics/*metabolism MH - Interleukin-1beta/metabolism MH - Lipoproteins, LDL/metabolism MH - Macrophages/*metabolism/pathology MH - Mice, Inbred C57BL MH - MicroRNAs/blood/genetics/*metabolism MH - *Plaque, Atherosclerotic MH - Prospective Studies MH - Ribonuclease III/metabolism MH - THP-1 Cells MH - Time Factors OTO - NOTNLM OT - Apoptosis OT - Atherosclerosis OT - Epigenetics OT - Inflammation OT - Macrophages EDAT- 2017/10/11 06:00 MHDA- 2018/07/22 06:00 CRDT- 2017/10/11 06:00 PHST- 2017/02/21 00:00 [received] PHST- 2017/08/08 00:00 [accepted] PHST- 2017/10/11 06:00 [pubmed] PHST- 2018/07/22 06:00 [medline] PHST- 2017/10/11 06:00 [entrez] AID - 4082334 [pii] AID - 10.1093/cvr/cvx157 [doi] PST - ppublish SO - Cardiovasc Res. 2017 Nov 1;113(13):1627-1638. doi: 10.1093/cvr/cvx157. PMID- 28892732 OWN - NLM STAT- MEDLINE DCOM- 20180319 LR - 20181202 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 133 DP - 2017 Nov TI - Clinical significance of diabetes likely induced by statins: Evidence from a large population-based cohort. PG - 60-68 LID - S0168-8227(17)30569-7 [pii] LID - 10.1016/j.diabres.2017.08.008 [doi] AB - AIM: To provide information on the extent to which type 2 diabetes more likely induced by statins affects the risk of macrovascular complications compared to diabetes unlikely induced by statins. METHODS: The 84,828 residents in the Italian Lombardy Region who were newly treated with statins between 2003 and 2005 were followed from the index statin prescription until 2009 (step-1 follow-up) to identify those starting antidiabetic therapy. The proportion of days of follow-up covered by statins measured adherence with statins. Cohort members who experienced diabetes were 1:3 matched with those who did not developed diabetes for gender, age and previous adherence with statin treatment. The 3321 diabetic - non-diabetic sets, were followed from the initial antidiabetic therapy until 2012 (step-2 follow-up) to estimate the hazard ratio (HR), and 95% Confidence Interval (CI), for macrovascular complications (proportional hazard models) associated with diabetes separately in each category of adherence with statins. RESULTS: During the step-1 follow-up, the risk of new-onset diabetes increased progressively with increasing adherence with statins. During the step-2 follow-up, the risk of macrovascular complications associated with diabetes decreased progressively from 1.70 (1.18-2.44), 1.41 (1.17-1.70), 1.30 (1.07-1.57) until 1.10 (0.40-2.80) as adherence with statins during the step-1 follow-up increased. CONCLUSIONS: Type 2 diabetes lost its association with increasing macrovascular risk when previous adherence with statins was very high, and thus the chance of its induction by the drug greater. Statin-dependent type 2 diabetes might be prognostically less adverse than diabetes unlikely induced by statins. CI - Copyright (c) 2017 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Corrao, Giovanni AU - Corrao G AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. FAU - Monzio Compagnoni, Matteo AU - Monzio Compagnoni M AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Rea, Federico AU - Rea F AD - Interuniversity Centre of Healthcare Research & Pharmacoepidemiology, Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Lombardy Region, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy; IRCSS Multimedica, Sesto San Giovanni, Milan, Italy. FAU - Mancia, Giuseppe AU - Mancia G AD - Faculty of Medicine, University of Milano-Bicocca, Milan, Italy. LA - eng PT - Journal Article DEP - 20170819 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Aged MH - Cohort Studies MH - Diabetes Mellitus, Type 2/*etiology MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Male MH - Middle Aged MH - Retrospective Studies OTO - NOTNLM OT - Adherence OT - Cohort study OT - Healthcare utilization database OT - Macrovascular outcomes OT - Statins OT - Type 2 diabetes EDAT- 2017/09/12 06:00 MHDA- 2018/03/20 06:00 CRDT- 2017/09/12 06:00 PHST- 2017/04/06 00:00 [received] PHST- 2017/07/13 00:00 [revised] PHST- 2017/08/14 00:00 [accepted] PHST- 2017/09/12 06:00 [pubmed] PHST- 2018/03/20 06:00 [medline] PHST- 2017/09/12 06:00 [entrez] AID - S0168-8227(17)30569-7 [pii] AID - 10.1016/j.diabres.2017.08.008 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2017 Nov;133:60-68. doi: 10.1016/j.diabres.2017.08.008. Epub 2017 Aug 19. PMID- 28758421 OWN - NLM STAT- MEDLINE DCOM- 20180709 LR - 20180712 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 24 IP - 17 DP - 2017 Nov TI - PCSK9 deficiency results in increased ectopic fat accumulation in experimental models and in humans. PG - 1870-1877 LID - 10.1177/2047487317724342 [doi] AB - Background Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low-density lipoprotein and very low-density lipoprotein receptor expression in several tissues. Here we evaluated whether PCSK9 may modulate the handling of triglycerides in the liver and peripheral tissues. Methods Subjects from the PLIC cohort were genotyped for the loss-of-function PCSK9 R46L variant and characterized for clinical and biochemical parameters, total and android fat mass, hepatic steatosis and epicardial fat thickness. Visceral adipose tissue and subcutaneous adipose tissue in PCSK9 KO and wild type mice were quantified by nuclear magnetic resonance imaging. Results Carriers of the R46L variant ( n = 13) had lower low-density lipoprotein cholesterol levels, higher body mass index and increased percentage of total and android fat masses compared with non-carriers ( n = 521). R46L variant associated with a two-fold increase prevalence of hepatic steatosis and higher epicardial fat thickness. These observations were replicated in PCSK9 KO mice, which showed increased visceral adipose tissue (but not subcutaneous adipose tissue) when fed chow or high-fat diet for 20 weeks, compared with wild type mice. Conclusions These data suggest that genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation. FAU - Baragetti, Andrea AU - Baragetti A AD - 1 Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. AD - 2 SISA Center for the Study of Atherosclerosis, Bassini Hospital, Italy. FAU - Balzarotti, Gloria AU - Balzarotti G AD - 1 Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. FAU - Grigore, Liliana AU - Grigore L AD - 2 SISA Center for the Study of Atherosclerosis, Bassini Hospital, Italy. AD - 3 IRCCS Multimedica Hospital, Italy. FAU - Pellegatta, Fabio AU - Pellegatta F AD - 2 SISA Center for the Study of Atherosclerosis, Bassini Hospital, Italy. AD - 3 IRCCS Multimedica Hospital, Italy. FAU - Guerrini, Uliano AU - Guerrini U AD - 1 Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. FAU - Pisano, Giuseppina AU - Pisano G AD - 4 Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, Universita degli Studi di Milano, Italy. FAU - Fracanzani, Anna L AU - Fracanzani AL AD - 4 Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, Universita degli Studi di Milano, Italy. FAU - Fargion, Silvia AU - Fargion S AD - 4 Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, Universita degli Studi di Milano, Italy. FAU - Norata, Giuseppe D AU - Norata GD AD - 1 Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. AD - 5 School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Western Australia. FAU - Catapano, Alberico L AU - Catapano AL AD - 1 Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. AD - 3 IRCCS Multimedica Hospital, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170731 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Cholesterol, LDL) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Pcsk9 protein, mouse) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM CIN - Eur J Prev Cardiol. 2017 Nov;24(17):1867-1869. PMID: 28958158 MH - Adipose Tissue/diagnostic imaging/metabolism/*physiopathology MH - *Adiposity/genetics MH - Animals MH - Body Mass Index MH - Cholesterol, LDL/blood MH - Genotype MH - Humans MH - Italy MH - Loss of Function Mutation MH - Male MH - Mice, Knockout MH - Phenotype MH - Proprotein Convertase 9/*deficiency/genetics MH - Time Factors OTO - NOTNLM OT - *PCSK9 OT - *ectopic fat OT - *loss of function mutations EDAT- 2017/08/02 06:00 MHDA- 2018/07/10 06:00 CRDT- 2017/08/01 06:00 PHST- 2017/08/02 06:00 [pubmed] PHST- 2018/07/10 06:00 [medline] PHST- 2017/08/01 06:00 [entrez] AID - 10.1177/2047487317724342 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2017 Nov;24(17):1870-1877. doi: 10.1177/2047487317724342. Epub 2017 Jul 31. PMID- 29056399 OWN - NLM STAT- MEDLINE DCOM- 20181030 LR - 20181113 IS - 1525-0024 (Electronic) IS - 1525-0016 (Linking) VI - 25 IP - 11 DP - 2017 Nov 1 TI - Targeting Cholesterol in Non-ischemic Heart Failure: A Role for LDLR Gene Therapy? PG - 2435-2437 LID - S1525-0016(17)30524-5 [pii] LID - 10.1016/j.ymthe.2017.10.008 [doi] FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS Multimedica Hospital, Sesto San Giovanni, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - IRCCS Multimedica Hospital, Sesto San Giovanni, Milan, Italy; Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia. Electronic address: danilo.norata@unimi.it. LA - eng PT - Journal Article PT - Comment DEP - 20171019 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (Cholesterol, LDL) RN - 0 (Receptors, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM CON - Mol Ther. 2017 Nov 1;25(11):2513-2525. PMID: 28822689 MH - *Cholesterol MH - Cholesterol, LDL MH - Genetic Therapy MH - *Heart Failure MH - Humans MH - Receptors, LDL/genetics PMC - PMC5675606 EDAT- 2017/10/24 06:00 MHDA- 2018/10/31 06:00 CRDT- 2017/10/24 06:00 PHST- 2017/10/24 06:00 [pubmed] PHST- 2018/10/31 06:00 [medline] PHST- 2017/10/24 06:00 [entrez] AID - S1525-0016(17)30524-5 [pii] AID - 10.1016/j.ymthe.2017.10.008 [doi] PST - ppublish SO - Mol Ther. 2017 Nov 1;25(11):2435-2437. doi: 10.1016/j.ymthe.2017.10.008. Epub 2017 Oct 19. PMID- 28965617 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20180611 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 29 DP - 2017 Oct TI - Detection of familial hypercholesterolemia in patients from a general practice database. PG - 25-30 LID - S1567-5688(17)30093-4 [pii] LID - 10.1016/j.atherosclerosissup.2017.07.004 [doi] AB - OBJECTIVES: Familial hypercholesterolemia (FH) is the most common monogenic lipid disorder associated with premature coronary heart disease. Early cholesterol-lowering therapy could effectively reduce cardiovascular disease morbidity and mortality in these patients. However, the majority of people with FH are undiagnosed, also due to low awareness and knowledge of FH in general practice, despite the high number of contacts GPs have with most of their patients which allows a systematic and effective approach to the detection of this condition. Here, we present a simple method to improve detection and to enhance awareness of FH in primary care using GP electronic health records. METHODS: We used electronic data from the Co.S. Consortium, involving more than 600 Italian affiliated GPs. Electronic data include demographic information, laboratory test results, recorded history of vascular disease and prescription of an HMG-CoA reductase inhibitor class medication. We performed a partial assessment of the Dutch Lipid Clinic Network (DLCN) score using those data that were recorded or available. We also sought to determine the prevalence of possible FH based on age-specific LDL-cholesterol thresholds employed by the diagnostic criteria of MEDPED and the non-age adjusted cut-off point (LDL-C >/=190 mg/dL). RESULTS: Data on LDL-C were available for 162,864 subjects. Mean LDL-C levels (SD) were 124.3 (33.6) mg/dL for non-treated subjects and 106.4 (38.5) mg/dL for statin-treated subjects. The cut-off of LDL-C >/=190 mg/dL yielded a prevalence of 2.9% among non-treated subjects and of 3.5% among statin-treated patients. Using the cut-off of >/=250 mg/dL, the prevalence was 0.1% among non-treated subjects and 0.3% among statin-treated patients. Using the cut-off >/=330 mg/dL (suggesting a probable diagnosis of FH according to the DLCN score) the prevalence was 0.01% and 0.02%. According to the stratification proposed by MEDPED criteria for the general population, the age-specific LDL-cholesterol thresholds identified 0.7% among non-treated subjects and 18.5% among statin-treated patients. CONCLUSION: The diagnosis of FH is possible in general medicine and should be an integral part of the GP's activity. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. Electronic address: manuela.casula@unimi.it. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Rossi Bernardi, Luigi AU - Rossi Bernardi L AD - IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Visconti, Marco AU - Visconti M AD - CoS (Consorzio Sanita) Study Center, Italy; FIMMG (Italian Federation of General Practitioner) Verona Study Center, Italy. FAU - Aronica, Alberto AU - Aronica A AD - CoS (Consorzio Sanita) Study Center, Italy; FIMMG (Italian Federation of General Practitioner) Verona Study Center, Italy. LA - eng PT - Journal Article PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Genetic Markers) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cholesterol/blood MH - DNA Mutational Analysis MH - Data Mining MH - *Databases, Factual MH - Electronic Health Records MH - *General Practice MH - Genetic Markers MH - Genetic Predisposition to Disease MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hyperlipoproteinemia Type II/*diagnosis/drug therapy/epidemiology/genetics MH - Italy/epidemiology MH - Mutation MH - Phenotype MH - Prevalence MH - Primary Health Care OTO - NOTNLM OT - Cardiovascular diseases OT - Familial hypercholesterolemia OT - Primary healthcare EDAT- 2017/10/03 06:00 MHDA- 2018/06/12 06:00 CRDT- 2017/10/03 06:00 PHST- 2017/10/03 06:00 [entrez] PHST- 2017/10/03 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] AID - S1567-5688(17)30093-4 [pii] AID - 10.1016/j.atherosclerosissup.2017.07.004 [doi] PST - ppublish SO - Atheroscler Suppl. 2017 Oct;29:25-30. doi: 10.1016/j.atherosclerosissup.2017.07.004. PMID- 28965616 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20180611 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 29 DP - 2017 Oct TI - Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study. PG - 17-24 LID - S1567-5688(17)30091-0 [pii] LID - 10.1016/j.atherosclerosissup.2017.07.002 [doi] AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). METHODS: We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). RESULTS: A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. CONCLUSIONS: This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. Electronic address: angela.pirillo@guestt.unimi.it. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Arca, Marcello AU - Arca M AD - Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy. FAU - Averna, Maurizio AU - Averna M AD - Biomedical Department of Internal Medicine and Specialistics (DIBIMIS), University of Palermo, Palermo, Italy. FAU - Bertolini, Stefano AU - Bertolini S AD - Department of Internal Medicine, University of Genoa, Genoa, Italy. FAU - Calandra, Sebastiano AU - Calandra S AD - Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. FAU - Tarugi, Patrizia AU - Tarugi P AD - Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. CN - LIPIGEN Group LA - eng PT - Journal Article PT - Multicenter Study PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (APOB protein, human) RN - 0 (Apolipoprotein B-100) RN - 0 (Genetic Markers) RN - 0 (LDLR protein, human) RN - 0 (Receptors, LDL) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM MH - Apolipoprotein B-100/genetics MH - Atherosclerosis/blood/genetics/prevention & control MH - Cholesterol/*blood MH - DNA Mutational Analysis MH - Databases, Factual MH - Genetic Markers MH - Genetic Predisposition to Disease MH - Heterozygote MH - Homozygote MH - Humans MH - Hyperlipoproteinemia Type II/blood/diagnosis/*genetics/therapy MH - Italy MH - *Mutation MH - Phenotype MH - Preliminary Data MH - Prognosis MH - Proprotein Convertase 9/genetics MH - Receptors, LDL/genetics MH - Risk Factors OTO - NOTNLM OT - APOB OT - Familial hypercholesterolemia OT - LDLR OT - PCSK9 OT - Pathogenic variants IR - Arca M FIR - Arca, Marcello IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Averna M FIR - Averna, Maurizio IRAD- UO Medicina Interna e Malattie Metaboliche, Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo e delle dislipidemie genetiche, A.O.U. Policlinico "P. Giaccone", Palermo, Italy. IR - Bertolini S FIR - Bertolini, Stefano IRAD- Centro Ambulatorio Dislipidemie - U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Calandra S FIR - Calandra, Sebastiano IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Catapano AL FIR - Catapano, Alberico Luigi IRAD- Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, IRCCS Multimedica, Milan, Italy. IR - Tarugi P FIR - Tarugi, Patrizia IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Pellegatta F FIR - Pellegatta, Fabio IRAD- Centro per lo Studio dell'Aterosclerosi, IRCCS Multimedica, Sesto San Giovanni, Italy. IR - Angelico F FIR - Angelico, Francesco IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Arca M FIR - Arca, Marcello IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Averna M FIR - Averna, Maurizio IRAD- UO Medicina Interna e Malattie Metaboliche, Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo e delle dislipidemie genetiche, A.O.U. Policlinico "P. Giaccone", Palermo, Italy. IR - Bartuli A FIR - Bartuli, Andrea IRAD- Ambulatorio Polispecialistico per le Malattie Rare, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy. IR - Biasucci G FIR - Biasucci, Giacomo IRAD- Centro Dislipidemie in Eta Evolutiva U.O. Pediatria e Neonatologia, Ospedale G. da Saliceto, Piacenza, Italy. IR - Biolo G FIR - Biolo, Gianni IRAD- S.S. Diabetologia e Malattie Metaboliche, U.C.O. Clinica Medica Generale, Azienda Ospedaliera Universitaria OORR, Ospedale Maggiore, Trieste, Italy. IR - Bonanni L FIR - Bonanni, Luca IRAD- Ambulatorio Dislipidemie, UO Medicina Interna, Ospedale dell'Angelo di Mestre, Venice, Italy. IR - Bonomo K FIR - Bonomo, Katia IRAD- AOU San Luigi Gonzaga, Orbassano, Turin, Italy. IR - Borghi C FIR - Borghi, Claudio IRAD- U.O. di Medicina Interna, Centro Aterosclerosi, Ambulatorio Dislipidemie, Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. IR - Bossi AC FIR - Bossi, Antonio Carlo IRAD- U.O.C. Malattie Endocrine e Centro regionale per il Diabete (Diabetologia), Ospedale "Treviglio-Caravaggio" di Treviglio, Bergamo, Italy. IR - Branchi A FIR - Branchi, Adriana IRAD- Ambulatorio Dislipidemie, Centro per lo Studio e la Prevenzione dell'Arteriosclerosi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy. IR - Carubbi F FIR - Carubbi, Francesca IRAD- U.O. Medicina ad indirizzo metabolico-nutrizionistico, Centro dislipidemie e centro di riferimento regionale per le malattie metaboliche rare, Nuovo Ospedale S. Agostino Estense (NOCSAE), Modena, Italy. IR - Cipollone F FIR - Cipollone, Francesco IRAD- Centro di alta specializzazione per la prevenzione dell'arteriosclerosi, centro di eccellenza ESH per l'ipertensione arteriosa, centro di riferimento regionale per le Dislipidemie, Ospedale Policlino S.S. Annunziata, Chieti, Italy. IR - Citroni N FIR - Citroni, Nadia IRAD- Centro Dislipidemia, UO Medicina Interna, Ospedale Santa Chiara, Trento, Italy. IR - Federici M FIR - Federici, Massimo IRAD- Dipartimento Medicina Interna - Centro per l'Aterosclerosi, Policlinico Universtario "Tor Vergata", Rome, Italy. IR - Ferri C FIR - Ferri, Claudio IRAD- Centro Ipertensione Arteriosa e Prevenzione Cardiovascolare, UOC Medicina Interna e Nefrologia, l'Aquila, Italy. IR - Fiorenza AM FIR - Fiorenza, Anna Maria IRAD- Dip. Medicina Interna, Centro Prevenzione e Cura dell'aterosclerosi, A.O. "Guido Salvini", Garbagnate Milanese, Milan, Italy. IR - Giaccari A FIR - Giaccari, Andrea IRAD- UOC Endocrinologia e Malattie del Metabolismo, Policlinico Gemelli, Rome, Italy. IR - Giorgino F FIR - Giorgino, Francesco IRAD- U.O. Endocrinologia, Ambulatori di Diabetologia e Malattie Metaboliche, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Guardamagna O FIR - Guardamagna, Ornella IRAD- U.O. Dislipidemie e Prevenzione Cardiovascolare, Ospedale Regina Margherita, Turin, Italy. IR - Iannuzzi A FIR - Iannuzzi, Arcangelo IRAD- U.O. Medicina Interna 5, Centro per le malattie da arteriosclerosi, AORN Cardarelli, Naples, Italy. IR - Iughetti L FIR - Iughetti, Lorenzo IRAD- U.O. Clinica Pediatrica, Policlinico di Modena, Modena, Italy. IR - Lupattelli G FIR - Lupattelli, Graziana IRAD- U.O. Medicina Interna Angiologia, Malattie da Arteriosclerosi, Ambulatorio di malattie del ricambio lipidico, Ospedale Santa Maria della Misericordia, Perugia, Italy. IR - Mandraffino G FIR - Mandraffino, Giuseppe IRAD- Dipartimento di Medicina Interna e Terapia Medica, Centro per la Diagnosi e Cura della Dislipidemia e Prevenzione dell'Aterosclerosi, A.O. Universitaria Policlinico "G. Martino", Messina, Italy. IR - Marcucci R FIR - Marcucci, Rossella IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Mombelli G FIR - Mombelli, Giuliana IRAD- Centro Universitario Dislipidemie "E. Grossi Paoletti", A.O. Ospedale Niguarda Ca' Granda, Milan, Italy. IR - Muntoni S FIR - Muntoni, Sandro IRAD- Centro per le Malattie Dismetaboliche e l'arteriosclerosi, Associazione ME.DI.CO Onlus, Cagliari, Italy. IR - Pecchioli V FIR - Pecchioli, Valerio IRAD- UOSD 'Prevenzione cardiovascolare', Dipartimento di Scienze Mediche, Azienda Sanitaria Locale Frosinone, Frosinone, Italy. IR - Pederiva C FIR - Pederiva, Cristina IRAD- U.O. Clinica Pediatrica, Servizio Clinico Dislipidemie per lo Studio e la Prevenzione dell'Aterosclerosi in eta pediatrica, Ospedale San Paolo, Milan, Italy. IR - Pipolo A FIR - Pipolo, Antonio IRAD- AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy. IR - Pisciotta L FIR - Pisciotta, Livia IRAD- U.O. Clinica di Medicina Interna 1, Ambulatorio Dislipidemie, IRCCS - A.O.U. San Martino - IST, Genoa, Italy. IR - Pujia A FIR - Pujia, Arturo IRAD- A.O.U. Mater Domini, Catanzaro, UOC di Nutrizione Clinica, Ambulatorio Dislipidemie, Catanzaro, Italy. IR - Purrello F FIR - Purrello, Francesco IRAD- U.O. Medicina Interna, Ospedale "Garibaldi Nesima", Catania, Italy. IR - Repetti E FIR - Repetti, Elena IRAD- Societa di Diabetologia e Malattie Metaboliche, Asti, Italy. IR - Rubba P FIR - Rubba, Paolo IRAD- Centro Coordinamento regionale per le Iperlipidemie, AOU Policlinico Federico II, Naples, Italy. IR - Sabba C FIR - Sabba, Carlo IRAD- U.O. di Medicina Interna "Frugoni" e Centro di Assistenza e Ricerca Malattie Rare, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Sampietro T FIR - Sampietro, Tiziana IRAD- U.O. Lipoaferesi, Centro Regionale di Riferimento per la diagnosi e cura delle Dislipidemie Ereditarie, Fondazione Toscana "G. Monasterio", Pisa, Italy. IR - Sarzani R FIR - Sarzani, Riccardo IRAD- Clinica di Medicina Interna e Geriatria, Centro di riferimento regionale ipertensione arteriosa e malattie cardiovascolari, INRCA Ospedale "Sestilli" e Azienda Ospedaliero-Universitaria Ospedali Riuniti di Torrette di Ancona, Ancona, Italy. IR - Tagliabue MP FIR - Tagliabue, Milena Paola IRAD- SCDU Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Universita di Torino, Turin, Italy. IR - Trenti C FIR - Trenti, Chiara IRAD- Arcispedale S. Maria Nuova - Azienda ospedaliera di Reggio Emilia, Reggio Emilia, Italy. IR - Vigna GB FIR - Vigna, Giovanni Battista IRAD- U. O Medicina Interna Universitaria, Centro per lo Studio delle Dislipidemie e dell'Aterosclerosi Azienda Ospedaliero-Universitaria di Ferrara, Polo di Cona, Ferrara, Italy. IR - Werba JP FIR - Werba, Jose Pablo IRAD- U.O. Ambulatorio Prevenzione Aterosclerosi IRCCS Cardiologico Monzino, Milan, Italy. IR - Zambon S FIR - Zambon, Sabina IRAD- U. O. Clinica Medica 1, Centro Dislipidemie e Aterosclerosi, A.O. di Padova, Padua, Italy. IR - Zenti MG FIR - Zenti, Maria Grazia IRAD- U.O. Endocrinologia, Diabetologia e Malattie del Metabolismo, Centro regionale specializzato per la diagnosi e terapia delle dislipidemie e aferesi terapeutica, A.O. Universitaria Integrata di Verona, Verona, Italy. IR - Montali A FIR - Montali, Anna IRAD- Centro per l'Arteriosclerosi, Dipartimento di Medicina Interna e Specialita Mediche, Universita di Roma "La Sapienza" - Azienda Policlinico Umberto I, Rome, Italy. IR - Noto D FIR - Noto, Davide IRAD- Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo, O.S di Medicina Interna e Malattie metaboliche, Universita degli Studi di Palermo, Palermo, Italy. IR - Bertolini S FIR - Bertolini, Stefano IRAD- Centro Ambulatorio Dislipidemie - U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Calandra S FIR - Calandra, Sebastiano IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Fortunato G FIR - Fortunato, Giuliana IRAD- Laboratorio di screening di Malattie Metaboliche, CEINGE - Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche, Azienda Ospedaliera Universitaria "Federico II", Naples, Italy. IR - Grigore L FIR - Grigore, Liliana IRAD- Centro per lo Studio dell'Aterosclerosi, IRCCS Multimedica, Sesto San Giovanni, Italy. IR - Del Ben M FIR - Del Ben, Maria IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Maranghi M FIR - Maranghi, Marianna IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Cefalu AB FIR - Cefalu, A Baldassarre IRAD- UO Medicina Interna e Malattie Metaboliche, Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo e delle dislipidemie genetiche, A.O.U. Policlinico "P. Giaccone", Palermo, Italy. IR - Buonuomo PS FIR - Buonuomo, Paola Sabrina IRAD- Ambulatorio Polispecialistico per le Malattie Rare, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy. IR - Capra ME FIR - Capra, Maria Elena IRAD- Centro Dislipidemie in Eta Evolutiva U.O. Pediatria e Neonatologia, Ospedale G. da Saliceto, Piacenza, Italy. IR - Vinci P FIR - Vinci, Pierandrea IRAD- S.S. Diabetologia e Malattie Metaboliche, U.C.O. Clinica Medica Generale, Azienda Ospedaliera Universitaria OORR, Ospedale Maggiore, Trieste, Italy. IR - D'Addato S FIR - D'Addato, Sergio IRAD- U.O. di Medicina Interna, Centro Aterosclerosi, Ambulatorio Dislipidemie, Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. IR - Galbiati S FIR - Galbiati, Stella IRAD- U.O.C. Malattie Endocrine e Centro regionale per il Diabete (Diabetologia), Ospedale "Treviglio-Caravaggio" di Treviglio, Bergamo, Italy. IR - Nascimbeni F FIR - Nascimbeni, Fabio IRAD- U.O. Medicina ad indirizzo metabolico-nutrizionistico, Centro dislipidemie e centro di riferimento regionale per le malattie metaboliche rare, Nuovo Ospedale S. Agostino Estense (NOCSAE), Modena, Italy. IR - Bucci M FIR - Bucci, Marco IRAD- Centro di alta specializzazione per la prevenzione dell'arteriosclerosi, centro di eccellenza ESH per l'ipertensione arteriosa, centro di riferimento regionale per le Dislipidemie, Ospedale Policlino S.S. Annunziata, Chieti, Italy. IR - Spagnoli W FIR - Spagnoli, Walter IRAD- Centro Dislipidemia, UO Medicina Interna, Ospedale Santa Chiara, Trento, Italy. IR - Cardolini I FIR - Cardolini, Iris IRAD- Dipartimento Medicina Interna - Centro per l'Aterosclerosi, Policlinico Universtario "Tor Vergata", Rome, Italy. IR - Cervelli N FIR - Cervelli, Nazzareno IRAD- Centro Ipertensione Arteriosa e Prevenzione Cardiovascolare, UOC Medicina Interna e Nefrologia, l'Aquila, Italy. IR - Emanuela C FIR - Emanuela, Colombo IRAD- Dip. Medicina Interna, Centro Prevenzione e Cura dell'aterosclerosi, A.O. "Guido Salvini", Garbagnate Milanese, Milan, Italy. IR - Sun VA FIR - Sun, Vinsin A IRAD- UOC Endocrinologia e Malattie del Metabolismo, Policlinico Gemelli, Rome, Italy. IR - Laviola L FIR - Laviola, Luigi IRAD- U.O. Endocrinologia, Ambulatori di Diabetologia e Malattie Metaboliche, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Bello F FIR - Bello, Francesca IRAD- U.O. Dislipidemie e Prevenzione Cardiovascolare, Ospedale Regina Margherita, Turin, Italy. IR - Chiariello G FIR - Chiariello, Giuseppe IRAD- U.O. Medicina Interna 5, Centro per le malattie da arteriosclerosi, AORN Cardarelli, Naples, Italy. IR - Predieri B FIR - Predieri, Barbara IRAD- U.O. Clinica Pediatrica, Policlinico di Modena, Modena, Italy. IR - Siepi D FIR - Siepi, Donatella IRAD- U.O. Medicina Interna Angiologia, Malattie da Arteriosclerosi, Ambulatorio di malattie del ricambio lipidico, Ospedale Santa Maria della Misericordia, Perugia, Italy. IR - Saitta A FIR - Saitta, Antonino IRAD- Dipartimento di Medicina Interna e Terapia Medica, Centro per la Diagnosi e Cura della Dislipidemia e Prevenzione dell'Aterosclerosi, A.O. Universitaria Policlinico "G. Martino", Messina, Italy. IR - Giusti B FIR - Giusti, Betti IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Pavanello C FIR - Pavanello, Chiara IRAD- Centro Universitario Dislipidemie "E. Grossi Paoletti", A.O. Ospedale Niguarda Ca' Granda, Milan, Italy. IR - Lussu M FIR - Lussu, Milena IRAD- Centro per le Malattie Dismetaboliche e l'arteriosclerosi, Associazione ME.DI.CO Onlus, Cagliari, Italy. IR - Prati L FIR - Prati, Lucia IRAD- UOSD 'Prevenzione cardiovascolare', Dipartimento di Scienze Mediche, Azienda Sanitaria Locale Frosinone, Frosinone, Italy. IR - Banderali G FIR - Banderali, Giuseppe IRAD- U.O. Clinica Pediatrica, Servizio Clinico Dislipidemie per lo Studio e la Prevenzione dell'Aterosclerosi in eta pediatrica, Ospedale San Paolo, Milan, Italy. IR - Balleari G FIR - Balleari, Giulia IRAD- U.O. Clinica di Medicina Interna 1, Ambulatorio Dislipidemie, IRCCS - A.O.U. San Martino - IST, Genoa, Italy. IR - Montalcini T FIR - Montalcini, Tiziana IRAD- A.O.U. Mater Domini, Catanzaro, UOC di Nutrizione Clinica, Ambulatorio Dislipidemie, Catanzaro, Italy. IR - Scicali R FIR - Scicali, Roberto IRAD- U.O. Medicina Interna, Ospedale "Garibaldi Nesima", Catania, Italy. IR - Gentile L FIR - Gentile, Luigi IRAD- Societa di Diabetologia e Malattie Metaboliche, Asti, Italy. IR - Gentile M FIR - Gentile, Marco IRAD- Centro Coordinamento regionale per le Iperlipidemie, AOU Policlinico Federico II, Naples, Italy. IR - Suppressa P FIR - Suppressa, Patrizia IRAD- U.O. di Medicina Interna "Frugoni" e Centro di Assistenza e Ricerca Malattie Rare, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Sbrana F FIR - Sbrana, Francesco IRAD- U.O. Lipoaferesi, Centro Regionale di Riferimento per la diagnosi e cura delle Dislipidemie Ereditarie, Fondazione Toscana "G. Monasterio", Pisa, Italy. IR - Cocci G FIR - Cocci, Guido IRAD- Clinica di Medicina Interna e Geriatria, Centro di riferimento regionale ipertensione arteriosa e malattie cardiovascolari, INRCA Ospedale "Sestilli" e Azienda Ospedaliero-Universitaria Ospedali Riuniti di Torrette di Ancona, Ancona, Italy. IR - Benso A FIR - Benso, Andrea IRAD- SCDU Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Universita di Torino, Turin, Italy. IR - Negri EA FIR - Negri, Emanuele Alberto IRAD- Arcispedale S. Maria Nuova - Azienda ospedaliera di Reggio Emilia, Reggio Emilia, Italy. IR - Ghirardello O FIR - Ghirardello, Omar IRAD- U. O Medicina Interna Universitaria, Centro per lo Studio delle Dislipidemie e dell'Aterosclerosi Azienda Ospedaliero-Universitaria di Ferrara, Polo di Cona, Ferrara, Italy. IR - Lorenzo V FIR - Lorenzo, Vigo IRAD- U.O. Ambulatorio Prevenzione Aterosclerosi IRCCS Cardiologico Monzino, Milan, Italy. IR - Zambon A FIR - Zambon, Alberto IRAD- U. O. Clinica Medica 1, Centro Dislipidemie e Aterosclerosi, A.O. di Padova, Padua, Italy. IR - Enzo B FIR - Enzo, Bonora IRAD- U.O. Endocrinologia, Diabetologia e Malattie del Metabolismo, Centro regionale specializzato per la diagnosi e terapia delle dislipidemie e aferesi terapeutica, A.O. Universitaria Integrata di Verona, Verona, Italy. IR - Minicocci I FIR - Minicocci, Ilenia IRAD- Centro per l'Arteriosclerosi, Dipartimento di Medicina Interna e Specialita Mediche, Universita di Roma "La Sapienza" - Azienda Policlinico Umberto I, Rome, Italy. IR - Spina R FIR - Spina, Rossella IRAD- Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo, O.S di Medicina Interna e Malattie metaboliche, Universita degli Studi di Palermo, Palermo, Italy. IR - Orlando C FIR - Orlando, Camilla IRAD- Centro Ambulatorio Dislipidemie - U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Tarugi P FIR - Tarugi, Patrizia IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Di Taranto MD FIR - Di Taranto, Maria Donata IRAD- Laboratorio di screening di Malattie Metaboliche, CEINGE - Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche, Azienda Ospedaliera Universitaria "Federico II", Naples, Italy. IR - Catapano AL FIR - Catapano, Alberico Luigi IRAD- Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, IRCCS Multimedica, Milan, Italy. IR - Casula M FIR - Casula, Manuela IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. IR - Chiodo L FIR - Chiodo, Lorenzo IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. IR - Garlaschelli K FIR - Garlaschelli, Katia IRAD- Centro per lo Studio dell'Aterosclerosi, Ospedale E. Bassini, Cinisello Balsamo, Milan, Italy. IR - Manzato E FIR - Manzato, Enzo IRAD- Dipartimento di Medicina (DIMED), Sezione Geriatrica, Universita di Padova, Padua, Italy. IR - Tragni E FIR - Tragni, Elena IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. EDAT- 2017/10/03 06:00 MHDA- 2018/06/12 06:00 CRDT- 2017/10/03 06:00 PHST- 2017/10/03 06:00 [entrez] PHST- 2017/10/03 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] AID - S1567-5688(17)30091-0 [pii] AID - 10.1016/j.atherosclerosissup.2017.07.002 [doi] PST - ppublish SO - Atheroscler Suppl. 2017 Oct;29:17-24. doi: 10.1016/j.atherosclerosissup.2017.07.002. PMID- 28965615 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20180611 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 29 DP - 2017 Oct TI - Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN). PG - 11-16 LID - S1567-5688(17)30090-9 [pii] LID - 10.1016/j.atherosclerosissup.2017.07.001 [doi] AB - BACKGROUND AND AIMS: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). METHODS: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. RESULTS AND CONCLUSIONS: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score >/=6. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Averna, Maurizio AU - Averna M AD - Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy. Electronic address: maurizio.averna@unipa.it. FAU - Cefalu, Angelo B AU - Cefalu AB AD - Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Noto, Davide AU - Noto D AD - Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy. FAU - Arca, Marcello AU - Arca M AD - Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy. FAU - Bertolini, Stefano AU - Bertolini S AD - Department of Internal Medicine, University of Genoa, Genoa, Italy. FAU - Calandra, Sebastiano AU - Calandra S AD - Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Tarugi, Patrizia AU - Tarugi P AD - Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy. CN - LIPIGEN Group LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Genetic Markers) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Atherosclerosis/blood/diagnosis/*genetics/prevention & control MH - Cholesterol/*blood MH - DNA Mutational Analysis MH - Databases, Factual MH - Genetic Markers MH - Genetic Predisposition to Disease MH - Humans MH - Hyperlipoproteinemia Type II/blood/diagnosis/*genetics/therapy MH - Italy MH - *Mutation MH - Phenotype MH - Prognosis MH - Program Development MH - Prospective Studies MH - Retrospective Studies MH - Risk Factors OTO - NOTNLM OT - Dyslipidemias OT - Genetic testing OT - National network IR - Arca M FIR - Arca, Marcello IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Averna M FIR - Averna, Maurizio IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Bertolini S FIR - Bertolini, Stefano IRAD- Centro Ambulatorio Dislipidemie - U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Calandra S FIR - Calandra, Sebastiano IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Catapano AL FIR - Catapano, Alberico Luigi IRAD- Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, and IRCCS Multimedica, Milan, Italy. IR - Tarugi P FIR - Tarugi, Patrizia IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Pellegatta F FIR - Pellegatta, Fabio IRAD- Centro per lo Studio dell'Aterosclerosi, IRCCS Multimedica, Sesto San Giovanni, Italy. IR - Angelico F FIR - Angelico, Francesco IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Arca M FIR - Arca, Marcello IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Averna M FIR - Averna, Maurizio IRAD- UO Medicina Clinica, Respiratoria e delle Urgenze, Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo, A.O.U. Policlinico "P. Giaccone", Palermo, Italy. IR - Bartuli A FIR - Bartuli, Andrea IRAD- Ambulatorio Polispecialistico per le Malattie Rare, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy. IR - Biasucci G FIR - Biasucci, Giacomo IRAD- Centro Dislipidemie in Eta Evolutiva U.O. Pediatria e Neonatologia, Ospedale G. da Saliceto, Piacenza, Italy. IR - Biolo G FIR - Biolo, Gianni IRAD- S.S. Diabetologia e Malattie Metaboliche, U.C.O. Clinica Medica Generale, Azienda Ospedaliera Universitaria OORR, Ospedale Maggiore, Trieste, Italy. IR - Bonanni L FIR - Bonanni, Luca IRAD- Ambulatorio Dislipidemie, UO Medicina Interna, Ospedale dell'Angelo di Mestre, Venice, Italy. IR - Bonomo K FIR - Bonomo, Katia IRAD- AOU San Luigi Gonzaga, Orbassano, Turin, Italy. IR - Borghi C FIR - Borghi, Claudio IRAD- U.O. di Medicina Interna, Centro Aterosclerosi, Ambulatorio Dislipidemie, Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. IR - Bossi AC FIR - Bossi, Antonio Carlo IRAD- U.O.C. Malattie Endocrine e Centro regionale per il Diabete (Diabetologia), Ospedale "Treviglio-Caravaggio" di Treviglio, Bergamo, Italy. IR - Branchi A FIR - Branchi, Adriana IRAD- Ambulatorio Dislipidemie, Centro per lo Studio e la Prevenzione dell'Arteriosclerosi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy. IR - Carubbi F FIR - Carubbi, Francesca IRAD- U.O. Medicina ad indirizzo metabolico-nutrizionistico, Centro dislipidemie e centro di riferimento regionale per le malattie metaboliche rare, Nuovo Ospedale S. Agostino Estense (NOCSAE), Modena, Italy. IR - Cipollone F FIR - Cipollone, Francesco IRAD- Centro di alta specializzazione per la prevenzione dell'arteriosclerosi, centro di eccellenza ESH per l'ipertensione arteriosa, centro di riferimento regionale per le Dislipidemie, Ospedale Policlino S.S. Annunziata, Chieti, Italy. IR - Citroni N FIR - Citroni, Nadia IRAD- Centro Dislipidemia, UO Medicina Interna, Ospedale Santa Chiara, Trento, Italy. IR - Federici M FIR - Federici, Massimo IRAD- Dipartimento Medicina Interna - Centro per l'Aterosclerosi, Policlinico Universtario "Tor Vergata", Rome, Italy. IR - Ferri C FIR - Ferri, Claudio IRAD- Centro Ipertensione Arteriosa e Prevenzione Cardiovascolare UOC Medicina Interna e Nefrologia, L'Aquila, Italy. IR - Fiorenza AM FIR - Fiorenza, Anna Maria IRAD- Dip. Medicina Interna, Centro Prevenzione e Cura dell'aterosclerosi, A.O. "Guido Salvini", Garbagnate Milanese, Milan, Italy. IR - Giaccari A FIR - Giaccari, Andrea IRAD- UOC Endocrinologia e Malattie del Metabolismo, Policlinico Gemelli, Rome, Italy. IR - Giorgino F FIR - Giorgino, Francesco IRAD- U.O. Endocrinologia, Ambulatori di Diabetologia e Malattie Metaboliche, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Guardamagna O FIR - Guardamagna, Ornella IRAD- U.O. Dislipidemie e Prevenzione Cardiovascolare, Ospedale Regina Margherita, Turin, Italy. IR - Iannuzzi A FIR - Iannuzzi, Arcangelo IRAD- U.O. Medicina Interna 5, Centro per le malattie da arteriosclerosi, AORN Cardarelli, Naples, Italy. IR - Iughetti L FIR - Iughetti, Lorenzo IRAD- U.O. Clinica Pediatrica, Policlinico di Modena, Modena, Italy. IR - Lupattelli G FIR - Lupattelli, Graziana IRAD- U.O. Medicina Interna Angiologia, Malattie da Arteriosclerosi, Ambulatorio di malattie del ricambio lipidico, Ospedale Santa Maria della Misericordia, Perugia, Italy. IR - Mandraffino G FIR - Mandraffino, Giuseppe IRAD- Dipartimento di Medicina Interna e Terapia Medica, Centro per la Diagnosi e Cura della Dislipidemia e Prevenzione dell'Aterosclerosi, A.O. Universitaria Policlinico "G.Martino", Messina, Italy. IR - Marcucci R FIR - Marcucci, Rossella IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Mombelli G FIR - Mombelli, Giuliana IRAD- Centro Universitario Dislipidemie "E. Grossi Paoletti", A.O. Ospedale Niguarda Ca' Granda, Milan, Italy. IR - Muntoni S FIR - Muntoni, Sandro IRAD- Centro per le Malattie Dismetaboliche e l'arteriosclerosi, Associazione ME.DI.CO Onlus, Cagliari, Italy. IR - Pecchioli V FIR - Pecchioli, Valerio IRAD- UOSD 'Prevenzione cardiovascolare', Dipartimento di Scienze Mediche, Azienda Sanitaria Locale Frosinone, Frosinone, Italy. IR - Pederiva C FIR - Pederiva, Cristina IRAD- U.O. Clinica Pediatrica, Servizio Clinico Dislipidemie per lo Studio e la Prevenzione dell'Aterosclerosi in eta pediatrica, Ospedale San Paolo, Milan, Italy. IR - Pipolo A FIR - Pipolo, Antonio IRAD- AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy. IR - Pisciotta L FIR - Pisciotta, Livia IRAD- U.O. Clinica di Medicina Interna 1, Ambulatorio Dislipidemie, IRCCS - A.O.U. San Martino - IST, Genoa, Italy. IR - Pujia A FIR - Pujia, Arturo IRAD- A.O.U. Mater Domini, Catanzaro, UOC di Nutrizione Clinica, Ambulatorio Dislipidemie, Catanzaro, Italy. IR - Purrello F FIR - Purrello, Francesco IRAD- U.O. Medicina Interna, Ospedale "Garibaldi Nesima", Catania, Italy. IR - Repetti E FIR - Repetti, Elena IRAD- Societa di Diabetologia e Malattie Metaboliche, Asti, Italy. IR - Rubba P FIR - Rubba, Paolo IRAD- Centro Coordinamento regionale per le Iperlipidemie, AOU Policlinico Federico II, Naples, Italy. IR - Sabba C FIR - Sabba, Carlo IRAD- U.O. di Medicina Interna "Frugoni" e Centro di Assistenza e Ricerca Malattie Rare, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Sampietro T FIR - Sampietro, Tiziana IRAD- U.O. Lipoaferesi, Centro Regionale di Riferimento per la diagnosi e cura delle Dislipidemie Ereditarie, Fondazione Toscana "G. Monasterio", Pisa, Italy. IR - Sarzani R FIR - Sarzani, Riccardo IRAD- Clinica di Medicina Interna e Geriatria, Centro di riferimento regionale ipertensione arteriosa e malattie cardiovascolari, INRCA Ospedale "Sestilli" e Azienda Ospedaliero-Universitaria Ospedali Riuniti di Torrette di Ancona, Ancona, Italy. IR - Tagliabue MP FIR - Tagliabue, Milena Paola IRAD- SCDU Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Universita di Torino, Turin, Italy. IR - Trenti C FIR - Trenti, Chiara IRAD- Arcispedale S. Maria Nuova - Azienda ospedaliera di Reggio Emilia, Reggio Emilia, Italy. IR - Vigna GB FIR - Vigna, Giovanni Battista IRAD- U. O Medicina Interna Universitaria, Centro per lo Studio delle Dislipidemie e dell'Aterosclerosi Azienda Ospedaliero-Universitaria di Ferrara, Polo di Cona, Ferrara, Italy. IR - Werba JP FIR - Werba, Jose Pablo IRAD- U.O. Ambulatorio Prevenzione Aterosclerosi IRCCS Cardiologico Monzino, Milan, Italy. IR - Zambon S FIR - Zambon, Sabina IRAD- U. O. Clinica Medica 1, Centro Dislipidemie e Aterosclerosi, A.O. di Padova, Padua, Italy. IR - Zenti MG FIR - Zenti, Maria Grazia IRAD- U.O. Endocrinologia, Diabetologia e Malattie del Metabolismo, Centro regionale specializzato per la diagnosi e terapia delle dislipidemie e aferesi terapeutica, A.O. Universitaria Integrata di Verona, Verona, Italy. IR - Montali A FIR - Montali, Anna IRAD- Centro per l'Arteriosclerosi, Dipartimento di Medicina Interna e Specialita Mediche, Universita di Roma "La Sapienza" - Azienda Policlinico Umberto I, Rome, Italy. IR - Noto D FIR - Noto, Davide IRAD- Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo, Universita degli Studi di Palermo, Palermo, Italy. IR - Bertolini S FIR - Bertolini, Stefano IRAD- Centro Ambulatorio Dislipidemie - U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Calandra S FIR - Calandra, Sebastiano IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Fortunato G FIR - Fortunato, Giuliana IRAD- Laboratorio di screening di Malattie Metaboliche, CEINGE - Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche, Azienda Ospedaliera Universitaria "Federico II", Naples, Italy. IR - Grigore L FIR - Grigore, Liliana IRAD- Centro per lo Studio dell'Aterosclerosi, IRCCS Multimedica, Sesto San Giovanni, Italy. IR - Del Ben M FIR - Del Ben, Maria IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Maranghi M FIR - Maranghi, Marianna IRAD- Dipartimento di Medicina Interna e Specialita Mediche "La Sapienza", A.O. Policlinico Umberto I, Rome, Italy. IR - Cefalu AB FIR - Cefalu, Angelo B IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Barbagallo CM FIR - Barbagallo, Carlo M IRAD- UO Medicina Clinica, Respiratoria e delle Urgenze, Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo, A.O.U. Policlinico "P. Giaccone", Palermo, Italy. IR - Buonuomo PS FIR - Buonuomo, Paola Sabrina IRAD- Ambulatorio Polispecialistico per le Malattie Rare, IRCCS Ospedale Pediatrico Bambino Gesu, Rome, Italy. IR - Capra ME FIR - Capra, Maria Elena IRAD- Centro Dislipidemie in Eta Evolutiva U.O. Pediatria e Neonatologia, Ospedale G. da Saliceto, Piacenza, Italy. IR - Vinci P FIR - Vinci, Pierandrea IRAD- S.S. Diabetologia e Malattie Metaboliche, U.C.O. Clinica Medica Generale, Azienda Ospedaliera Universitaria OORR, Ospedale Maggiore, Trieste, Italy. IR - D'Addato S FIR - D'Addato, Sergio IRAD- U.O. di Medicina Interna, Centro Aterosclerosi, Ambulatorio Dislipidemie, Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. IR - Galbiati S FIR - Galbiati, Stella IRAD- U.O.C. Malattie Endocrine e Centro regionale per il Diabete (Diabetologia), Ospedale "Treviglio-Caravaggio" di Treviglio, Bergamo, Italy. IR - Nascimbeni F FIR - Nascimbeni, Fabio IRAD- U.O. Medicina ad indirizzo metabolico-nutrizionistico, Centro dislipidemie e centro di riferimento regionale per le malattie metaboliche rare, Nuovo Ospedale S. Agostino Estense (NOCSAE), Modena, Italy. IR - Bucci M FIR - Bucci, Marco IRAD- Centro di alta specializzazione per la prevenzione dell'arteriosclerosi, centro di eccellenza ESH per l'ipertensione arteriosa, centro di riferimento regionale per le Dislipidemie, Ospedale Policlino S.S. Annunziata, Chieti, Italy. IR - Spagnoli W FIR - Spagnoli, Walter IRAD- Centro Dislipidemia, UO Medicina Interna, Ospedale Santa Chiara, Trento, Italy. IR - Cardolini I FIR - Cardolini, Iris IRAD- Dipartimento Medicina Interna - Centro per l'Aterosclerosi, Policlinico Universtario "Tor Vergata", Rome, Italy. IR - Cervelli N FIR - Cervelli, Nazzareno IRAD- Centro Ipertensione Arteriosa e Prevenzione Cardiovascolare UOC Medicina Interna e Nefrologia, L'Aquila, Italy. IR - Emanuela C FIR - Emanuela, Colombo IRAD- Dip. Medicina Interna, Centro Prevenzione e Cura dell'aterosclerosi, A.O. "Guido Salvini", Garbagnate Milanese, Milan, Italy. IR - Vinsin AS FIR - Vinsin, A Sun IRAD- UOC Endocrinologia e Malattie del Metabolismo, Policlinico Gemelli, Rome, Italy. IR - Laviola L FIR - Laviola, Luigi IRAD- U.O. Endocrinologia, Ambulatori di Diabetologia e Malattie Metaboliche, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Bello F FIR - Bello, Francesca IRAD- U.O. Dislipidemie e Prevenzione Cardiovascolare, Ospedale Regina Margherita, Turin, Italy. IR - Chiariello G FIR - Chiariello, Giuseppe IRAD- U.O. Medicina Interna 5, Centro per le malattie da arteriosclerosi, AORN Cardarelli, Naples, Italy. IR - Predieri B FIR - Predieri, Barbara IRAD- U.O. Clinica Pediatrica, Policlinico di Modena, Modena, Italy. IR - Siepi D FIR - Siepi, Donatella IRAD- U.O. Medicina Interna Angiologia, Malattie da Arteriosclerosi, Ambulatorio di malattie del ricambio lipidico, Ospedale Santa Maria della Misericordia, Perugia, Italy. IR - Saitta A FIR - Saitta, Antonino IRAD- Dipartimento di Medicina Interna e Terapia Medica, Centro per la Diagnosi e Cura della Dislipidemia e Prevenzione dell'Aterosclerosi, A.O. Universitaria Policlinico "G.Martino", Messina, Italy. IR - Giusti B FIR - Giusti, Betti IRAD- Ambulatorio Malattie Aterotrombotiche, AOUC Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. IR - Pavanello C FIR - Pavanello, Chiara IRAD- Centro Universitario Dislipidemie "E. Grossi Paoletti", A.O. Ospedale Niguarda Ca' Granda, Milan, Italy. IR - Lussu M FIR - Lussu, Milena IRAD- Centro per le Malattie Dismetaboliche e l'arteriosclerosi, Associazione ME.DI.CO Onlus, Cagliari, Italy. IR - Prati L FIR - Prati, Lucia IRAD- UOSD 'Prevenzione cardiovascolare', Dipartimento di Scienze Mediche, Azienda Sanitaria Locale Frosinone, Frosinone, Italy. IR - Banderali G FIR - Banderali, Giuseppe IRAD- U.O. Clinica Pediatrica, Servizio Clinico Dislipidemie per lo Studio e la Prevenzione dell'Aterosclerosi in eta pediatrica, Ospedale San Paolo, Milan, Italy. IR - Balleari G FIR - Balleari, Giulia IRAD- U.O. Clinica di Medicina Interna 1, Ambulatorio Dislipidemie, IRCCS - A.O.U. San Martino - IST, Genoa, Italy. IR - Montalcini T FIR - Montalcini, Tiziana IRAD- A.O.U. Mater Domini, Catanzaro, UOC di Nutrizione Clinica, Ambulatorio Dislipidemie, Catanzaro, Italy. IR - Scicali R FIR - Scicali, Roberto IRAD- U.O. Medicina Interna, Ospedale "Garibaldi Nesima", Catania, Italy. IR - Gentile L FIR - Gentile, Luigi IRAD- Societa di Diabetologia e Malattie Metaboliche, Asti, Italy. IR - Gentile M FIR - Gentile, Marco IRAD- Centro Coordinamento regionale per le Iperlipidemie, AOU Policlinico Federico II, Naples, Italy. IR - Suppressa P FIR - Suppressa, Patrizia IRAD- U.O. di Medicina Interna "Frugoni" e Centro di Assistenza e Ricerca Malattie Rare, A.O. Universitaria Policlinico Consorziale, Universita degli Studi di Bari "Aldo Moro", Bari, Italy. IR - Sbrana F FIR - Sbrana, Francesco IRAD- U.O. Lipoaferesi, Centro Regionale di Riferimento per la diagnosi e cura delle Dislipidemie Ereditarie, Fondazione Toscana "G. Monasterio", Pisa, Italy. IR - Cocci G FIR - Cocci, Guido IRAD- Clinica di Medicina Interna e Geriatria, Centro di riferimento regionale ipertensione arteriosa e malattie cardiovascolari, INRCA Ospedale "Sestilli" e Azienda Ospedaliero-Universitaria Ospedali Riuniti di Torrette di Ancona, Ancona, Italy. IR - Benso A FIR - Benso, Andrea IRAD- SCDU Endocrinologia, Diabetologia e Metabolismo, Dipartimento di Scienze Mediche, Universita di Torino, Turin, Italy. IR - Negri EA FIR - Negri, Emanuele Alberto IRAD- Arcispedale S. Maria Nuova - Azienda ospedaliera di Reggio Emilia, Reggio Emilia, Italy. IR - Ghirardello O FIR - Ghirardello, Omar IRAD- U. O Medicina Interna Universitaria, Centro per lo Studio delle Dislipidemie e dell'Aterosclerosi Azienda Ospedaliero-Universitaria di Ferrara, Polo di Cona, Ferrara, Italy. IR - Lorenzo V FIR - Lorenzo, Vigo IRAD- U.O. Ambulatorio Prevenzione Aterosclerosi IRCCS Cardiologico Monzino, Milan, Italy. IR - Zambon A FIR - Zambon, Alberto IRAD- U. O. Clinica Medica 1, Centro Dislipidemie e Aterosclerosi, A.O. di Padova, Padua, Italy. IR - Enzo B FIR - Enzo, Bonora IRAD- U.O. Endocrinologia, Diabetologia e Malattie del Metabolismo, Centro regionale specializzato per la diagnosi e terapia delle dislipidemie e aferesi terapeutica, A.O. Universitaria Integrata di Verona, Verona, Italy. IR - Minicocci I FIR - Minicocci, Ilenia IRAD- Centro per l'Arteriosclerosi, Dipartimento di Medicina Interna e Specialita Mediche, Universita di Roma "La Sapienza" - Azienda Policlinico Umberto I, Rome, Italy. IR - Spina R FIR - Spina, Rossella IRAD- Centro di riferimento regionale per la prevenzione, diagnosi e cura delle malattie rare del metabolismo, Universita degli Studi di Palermo, Palermo, Italy. IR - Orlando C FIR - Orlando, Camilla IRAD- Centro Ambulatorio Dislipidemie - U.O. Clinica di Medicina Interna 1, O. Universitaria San Martino, Genua, Italy. IR - Tarugi P FIR - Tarugi, Patrizia IRAD- Laboratorio Sequenziamento Genomico, Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, Modena, Italy. IR - Di Taranto MD FIR - Di Taranto, Maria Donata IRAD- Laboratorio di screening di Malattie Metaboliche, CEINGE - Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche, Azienda Ospedaliera Universitaria "Federico II", Naples, Italy. IR - Catapano AL FIR - Catapano, Alberico Luigi IRAD- Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, and IRCCS Multimedica, Milan, Italy. IR - Casula M FIR - Casula, Manuela IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. IR - Chiodo L FIR - Chiodo, Lorenzo IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. IR - Garlaschelli K FIR - Garlaschelli, Katia IRAD- Centro per lo Studio dell'Aterosclerosi, Ospedale E. Bassini, Cinisello Balsamo, Milan, Italy. IR - Manzato E FIR - Manzato, Enzo IRAD- Dipartimento di Medicina (DIMED), Sezione Geriatrica, Universita di Padova, Padua, Italy. IR - Tragni E FIR - Tragni, Elena IRAD- Centro Universitario di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. EDAT- 2017/10/03 06:00 MHDA- 2018/06/12 06:00 CRDT- 2017/10/03 06:00 PHST- 2017/10/03 06:00 [entrez] PHST- 2017/10/03 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] AID - S1567-5688(17)30090-9 [pii] AID - 10.1016/j.atherosclerosissup.2017.07.001 [doi] PST - ppublish SO - Atheroscler Suppl. 2017 Oct;29:11-16. doi: 10.1016/j.atherosclerosissup.2017.07.001. PMID- 28846118 OWN - NLM STAT- MEDLINE DCOM- 20170920 LR - 20181113 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 318 IP - 10 DP - 2017 Sep 12 TI - Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk. PG - 947-956 LID - 10.1001/jama.2017.11467 [doi] AB - Importance: Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered. Objective: To estimate the association between changes in levels of LDL-C (and other lipoproteins) and the risk of cardiovascular events related to variants in the CETP gene, both alone and in combination with variants in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene. Design, Setting, and Participants: Mendelian randomization analyses evaluating the association between CETP and HMGCR scores, changes in lipid and lipoprotein levels, and the risk of cardiovascular events involving 102837 participants from 14 cohort or case-control studies conducted in North America or the United Kingdom between 1948 and 2012. The associations with cardiovascular events were externally validated in 189539 participants from 48 studies conducted between 2011 and 2015. Exposures: Differences in mean high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein B (apoB) levels in participants with CETP scores at or above vs below the median. Main Outcomes and Measures: Odds ratio (OR) for major cardiovascular events. Results: The primary analysis included 102837 participants (mean age, 59.9 years; 58% women) who experienced 13821 major cardiovascular events. The validation analyses included 189539 participants (mean age, 58.5 years; 39% women) with 62240 cases of coronary heart disease (CHD). Considered alone, the CETP score was associated with higher levels of HDL-C, lower LDL-C, concordantly lower apoB, and a corresponding lower risk of major vascular events (OR, 0.946 [95% CI, 0.921-0.972]) that was similar in magnitude to the association between the HMGCR score and risk of major cardiovascular events per unit change in levels of LDL-C (and apoB). When combined with the HMGCR score, the CETP score was associated with the same reduction in LDL-C levels but an attenuated reduction in apoB levels and a corresponding attenuated nonsignificant risk of major cardiovascular events (OR, 0.985 [95% CI, 0.955-1.015]). In external validation analyses, a genetic score consisting of variants with naturally occurring discordance between levels of LDL-C and apoB was associated with a similar risk of CHD per unit change in apoB level (OR, 0.782 [95% CI, 0.720-0.845] vs 0.793 [95% CI, 0.774-0.812]; P = .79 for difference), but a significantly attenuated risk of CHD per unit change in LDL-C level (OR, 0.916 [95% CI, 0.890-0.943] vs 0.831 [95% CI, 0.816-0.847]; P < .001) compared with a genetic score associated with concordant changes in levels of LDL-C and apoB. Conclusions and Relevance: Combined exposure to variants in the genes that encode the targets of CETP inhibitors and statins was associated with discordant reductions in LDL-C and apoB levels and a corresponding risk of cardiovascular events that was proportional to the attenuated reduction in apoB but significantly less than expected per unit change in LDL-C. The clinical benefit of lowering LDL-C levels may therefore depend on the corresponding reduction in apoB-containing lipoprotein particles. FAU - Ference, Brian A AU - Ference BA AD - Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, Michigan. AD - Institute for Advanced Studies, University of Bristol, Bristol, United Kingdom. FAU - Kastelein, John J P AU - Kastelein JJP AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Irving Institute for Clinical and Translational Research, Columbia University College of Physicians and Surgeons, New York, New York. FAU - Chapman, M John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), Pitie-Salpetriere University Hospital, Paris, France. FAU - Nicholls, Stephen J AU - Nicholls SJ AD - South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom. FAU - Packard, Chris J AU - Packard CJ AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. FAU - Laufs, Ulrich AU - Laufs U AD - Department of Cardiology, University of Leipzig, Leipzig, Germany. FAU - Brook, Robert D AU - Brook RD AD - Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor. FAU - Oliver-Williams, Clare AU - Oliver-Williams C AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. FAU - Butterworth, Adam S AU - Butterworth AS AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. AD - National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom. FAU - Danesh, John AU - Danesh J AD - MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. AD - National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom. AD - Wellcome Trust Sanger Institute, Hinxton, United Kingdom. FAU - Smith, George Davey AU - Smith GD AD - MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milano, Italy. FAU - Sabatine, Marc S AU - Sabatine MS AD - Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. LA - eng GR - MC_UU_12013/1/Medical Research Council/United Kingdom GR - MR/L003120/1/Medical Research Council/United Kingdom GR - RG/08/014/24067/British Heart Foundation/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Anticholesteremic Agents) RN - 0 (Apolipoproteins B) RN - 0 (CETP protein, human) RN - 0 (Cholesterol Ester Transfer Proteins) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - EC 1.1.1.- (HMGCR protein, human) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) SB - AIM SB - IM CIN - JAMA. 2017 Sep 12;318(10 ):915-917. PMID: 28846117 MH - Anticholesteremic Agents/therapeutic use MH - Apolipoproteins B/*blood MH - Cardiovascular Diseases/*genetics/prevention & control MH - Cholesterol Ester Transfer Proteins/*antagonists & inhibitors/genetics MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/*blood MH - Female MH - *Genetic Variation MH - Humans MH - Hydroxymethylglutaryl CoA Reductases/*genetics MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypercholesterolemia/blood/drug therapy/*genetics MH - Male MH - Mendelian Randomization Analysis MH - Middle Aged MH - Risk Factors PMC - PMC5710502 EDAT- 2017/08/29 06:00 MHDA- 2017/09/21 06:00 CRDT- 2017/08/29 06:00 PHST- 2017/08/29 06:00 [pubmed] PHST- 2017/09/21 06:00 [medline] PHST- 2017/08/29 06:00 [entrez] AID - 2650886 [pii] AID - 10.1001/jama.2017.11467 [doi] PST - ppublish SO - JAMA. 2017 Sep 12;318(10):947-956. doi: 10.1001/jama.2017.11467. PMID- 28859793 OWN - NLM STAT- MEDLINE DCOM- 20170913 LR - 20170913 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 70 IP - 10 DP - 2017 Sep 5 TI - Optimizing Cholesterol Treatment in Patients With Muscle Complaints. PG - 1290-1301 LID - S0735-1097(17)38966-0 [pii] LID - 10.1016/j.jacc.2017.07.752 [doi] AB - Statins are highly effective for preventing cardiovascular events by reducing low-density lipoprotein cholesterol (LDL-C). However, many patients taking statins report muscle-related symptoms that prevent the use of guideline recommended doses. Patients with reported intolerance to statins have a high risk of cardiovascular events. Clinical strategies that optimize cardiovascular risk reduction through LDL-C lowering need to be applied in patients experiencing intolerable side effects that they attribute to statins. In this paper, the authors review definitions of statin intolerance, propose algorithms to better define statin intolerance, and describe approaches to optimize cardiovascular risk reduction among individuals reporting statin-associated muscle symptoms. CI - Copyright (c) 2017 American College of Cardiology Foundation. All rights reserved. FAU - Rosenson, Robert S AU - Rosenson RS AD - Department of Medicine, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: robert.rosenson@mssm.edu. FAU - Baker, Steven AU - Baker S AD - Department of Medicine, Neuromuscular Disease Clinic, McMaster University, Hamilton, Ontario, Canada. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, Medical University of Lodz, Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland. FAU - Borow, Kenneth M AU - Borow KM AD - National Medication Safety, Outcomes and Adherence Program, MediMergent, Rockville, Maryland. FAU - Braun, Lynne T AU - Braun LT AD - Department of Adult Health and Gerentologic Nursing, College of Nursing, Rush University Medical Center, Chicago, Illinois. FAU - Bruckert, Eric AU - Bruckert E AD - Institute of Cardiometabolism and Nutrition (ICAN), Endocrinology Department, Hopital Pitie Salpetriere, Paris, France. FAU - Brunham, Liam R AU - Brunham LR AD - Department of Medicine, University of Vancouver, British Columbia, Canada. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy. FAU - Elam, Marshall B AU - Elam MB AD - Departments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee. FAU - Mancini, G B John AU - Mancini GBJ AD - Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Moriarty, Patrick M AU - Moriarty PM AD - Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas. FAU - Morris, Pamela B AU - Morris PB AD - Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina. FAU - Muntner, Paul AU - Muntner P AD - Department of Epidemiology, University of Alabama Birmingham, Birmingham, Alabama. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London, United Kingdom. FAU - Stroes, Erik S AU - Stroes ES AD - Department of Vascular Medicine, AMC, Amsterdam, the Netherlands. FAU - Taylor, Beth A AU - Taylor BA AD - Department of Kinesiology, University of Connecticut, Storrs, Connecticut; Division of Cardiology, Hartford Hospital, Hartford, Connecticut. FAU - Taylor, Valerie H AU - Taylor VH AD - Department of Psychiatry, University of Toronto, Women's College Hospital, Toronto, Ontario, Canada. FAU - Watts, Gerald F AU - Watts GF AD - Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital; School of Medicine, University of Western Australia, Perth, Western Australia. FAU - Thompson, Paul D AU - Thompson PD AD - Division of Cardiology, Hartford Hospital, Hartford, Connecticut. LA - eng PT - Journal Article PT - Review PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Anticholesteremic Agents) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) SB - AIM SB - IM MH - Anticholesteremic Agents/*adverse effects/therapeutic use MH - Cardiovascular Diseases/blood/*prevention & control MH - Cholesterol/*blood MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/therapeutic use MH - Muscle, Skeletal/*drug effects MH - Muscular Diseases/*chemically induced MH - Risk Factors OTO - NOTNLM OT - cardiovascular disease OT - low-density lipoprotein OT - myalgia OT - myopathy OT - statin intolerance EDAT- 2017/09/02 06:00 MHDA- 2017/09/14 06:00 CRDT- 2017/09/02 06:00 PHST- 2017/05/21 00:00 [received] PHST- 2017/07/20 00:00 [revised] PHST- 2017/07/21 00:00 [accepted] PHST- 2017/09/02 06:00 [entrez] PHST- 2017/09/02 06:00 [pubmed] PHST- 2017/09/14 06:00 [medline] AID - S0735-1097(17)38966-0 [pii] AID - 10.1016/j.jacc.2017.07.752 [doi] PST - ppublish SO - J Am Coll Cardiol. 2017 Sep 5;70(10):1290-1301. doi: 10.1016/j.jacc.2017.07.752. PMID- 28919772 OWN - NLM STAT- MEDLINE DCOM- 20171030 LR - 20181113 IS - 1178-2048 (Electronic) IS - 1176-6344 (Linking) VI - 13 DP - 2017 TI - Anti-PCSK9 antibodies for the treatment of heterozygous familial hypercholesterolemia: patient selection and perspectives. PG - 343-351 LID - 10.2147/VHRM.S130338 [doi] AB - Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels from birth, which exposes the arteries to high levels of atherogenic lipoproteins lifelong and results in a significantly increased risk of premature cardiovascular events. The diagnosis of FH, followed by an appropriate and early treatment is critical to reduce the cardiovascular burden in this population. Phase I-III clinical trials showed the benefit of proprotein convertase subtilisin kexin 9 inhibitors, both alirocumab and evolocumab, in these patients with an average low-density lipoprotein cholesterol reduction ranging from -40% to -60%. The aim of this review is to address the unmet needs in cholesterol management, elucidate the biology and the clinical benefit of proprotein convertase subtilisin kexin 9 inhibition and finally discuss the open gaps and future directions in the treatment of patients with heterozygous FH. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano. AD - IRCCS Multimedica Hospital, Sesto San Giovanni. FAU - Pirillo, Angela AU - Pirillo A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano. AD - IRCCS Multimedica Hospital, Sesto San Giovanni. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano. AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia. LA - eng PT - Journal Article PT - Review DEP - 20170904 PL - New Zealand TA - Vasc Health Risk Manag JT - Vascular health and risk management JID - 101273479 RN - 0 (Antibodies, Monoclonal) RN - 0 (Anticholesteremic Agents) RN - 0 (Biomarkers) RN - 0 (Cholesterol, LDL) RN - 0 (Serine Proteinase Inhibitors) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - LKC0U3A8NJ (evolocumab) RN - PP0SHH6V16 (alirocumab) SB - IM MH - Adult MH - Animals MH - Antibodies, Monoclonal/adverse effects/*therapeutic use MH - Anticholesteremic Agents/adverse effects/*therapeutic use MH - Biomarkers/blood MH - Cholesterol, LDL/*blood MH - Clinical Trials as Topic MH - Evidence-Based Medicine MH - Female MH - Genetic Predisposition to Disease MH - *Heterozygote MH - Humans MH - Hyperlipoproteinemia Type II/blood/*drug therapy/enzymology/genetics MH - Male MH - Phenotype MH - Proprotein Convertase 9/*antagonists & inhibitors/immunology/metabolism MH - Serine Proteinase Inhibitors/adverse effects/*therapeutic use MH - Treatment Outcome MH - Young Adult PMC - PMC5590683 OTO - NOTNLM OT - HeFH OT - alirocumab OT - cholesterol OT - dyslipidemia OT - evolocumab COIS- Disclosure The authors have received research funding, and/or honoraria for advisory boards, consultancy or speaker bureau from Aegerion (ALC, GDN), Amgen (ALC, GDN), AstraZeneca (ALC), Eli Lilly (ALC), Genzyme (ALC), Mediolanum (ALC), Merck or MSD (ALC), Pfizer (ALC, GDN), Recordati (ALC, GDN), Rottapharm (ALC), Sanofi-Regeneron (ALC, GDN), Sigma-Tau (ALC). AP reports no conflicts of interest in this work. EDAT- 2017/09/19 06:00 MHDA- 2017/10/31 06:00 CRDT- 2017/09/19 06:00 PHST- 2017/09/19 06:00 [entrez] PHST- 2017/09/19 06:00 [pubmed] PHST- 2017/10/31 06:00 [medline] AID - 10.2147/VHRM.S130338 [doi] AID - vhrm-13-343 [pii] PST - epublish SO - Vasc Health Risk Manag. 2017 Sep 4;13:343-351. doi: 10.2147/VHRM.S130338. eCollection 2017. PMID- 28728483 OWN - NLM STAT- MEDLINE DCOM- 20180131 LR - 20181202 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 24 IP - 14 DP - 2017 Sep TI - PCSK9 inhibition in statin-intolerant HeFH patients: What's new? PG - 1525-1527 LID - 10.1177/2047487317721980 [doi] FAU - Casula, Manuela AU - Casula M AD - 1 Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A AD - 2 Center for the Study of Atherosclerosis, E Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - 3 IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - 4 Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. AD - 5 School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - 1 Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. AD - 3 IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. LA - eng PT - Editorial PT - Comment DEP - 20170721 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM CON - Eur J Prev Cardiol. 2017 Sep;24(14 ):1528-1531. PMID: 28555526 MH - Cholesterol, LDL MH - Humans MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors MH - Hyperlipoproteinemia Type II MH - *Proprotein Convertase 9 EDAT- 2017/07/22 06:00 MHDA- 2018/02/01 06:00 CRDT- 2017/07/22 06:00 PHST- 2017/07/22 06:00 [pubmed] PHST- 2018/02/01 06:00 [medline] PHST- 2017/07/22 06:00 [entrez] AID - 10.1177/2047487317721980 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2017 Sep;24(14):1525-1527. doi: 10.1177/2047487317721980. Epub 2017 Jul 21. PMID- 28444290 OWN - NLM STAT- MEDLINE DCOM- 20180717 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 38 IP - 32 DP - 2017 Aug 21 TI - Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. PG - 2459-2472 LID - 10.1093/eurheartj/ehx144 [doi] AB - Aims: To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results: We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion: Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD. CI - (c) The Author 2017. Published on behalf of the European Society of Cardiology FAU - Ference, Brian A AU - Ference BA AD - Division of Translational Research and Clinical Epidemiology, Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, MI 48202, USA. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA. FAU - Graham, Ian AU - Graham I AD - Trinity College Dublin, Ireland. FAU - Ray, Kausik K AU - Ray KK AD - Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, Imperial College, London, UK. FAU - Packard, Chris J AU - Packard CJ AD - College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK. FAU - Bruckert, Eric AU - Bruckert E AD - INSERM UMRS1166, Department of Endocrinology-Metabolism, ICAN - Institute of CardioMetabolism and Nutrition, AP-HP, Hopital de la Pitie, Paris, France. FAU - Hegele, Robert A AU - Hegele RA AD - Department of Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. FAU - Krauss, Ronald M AU - Krauss RM AD - Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. FAU - Raal, Frederick J AU - Raal FJ AD - Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. FAU - Schunkert, Heribert AU - Schunkert H AD - Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Munich 80636, Germany. AD - Deutsches Zentrum fur Herz und Kreislauferkrankungen (DZHK), Partner Site Munich Heart Alliance, Munich 81377, Germany. FAU - Watts, Gerald F AU - Watts GF AD - Lipid Disorders Clinic, Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia. FAU - Boren, Jan AU - Boren J AD - Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden. FAU - Fazio, Sergio AU - Fazio S AD - Department of Medicine, Center for Preventive Cardiology of the Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA. FAU - Horton, Jay D AU - Horton JD AD - Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Masana, Luis AU - Masana L AD - Research Unit of Lipids and Atherosclerosis, University Rovira i Virgili, C. Sant Llorenc 21, Reus 43201, Spain. FAU - Nicholls, Stephen J AU - Nicholls SJ AD - South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark. AD - Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. AD - The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark. FAU - van de Sluis, Bart AU - van de Sluis B AD - Department of Pediatrics, Molecular Genetics Section, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen AV 9713, The Netherlands. FAU - Taskinen, Marja-Riitta AU - Taskinen MR AD - Helsinki University Central Hospital and Research Programs' Unit, Diabetes and Obesity, Heart and Lung Centre, University of Helsinki, Helsinki, Finland. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Hacettepe University, Ankara, Turkey. FAU - Landmesser, Ulf AU - Landmesser U AD - Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA. AD - INSERM UMRS1166, Department of Endocrinology-Metabolism, ICAN - Institute of CardioMetabolism and Nutrition, AP-HP, Hopital de la Pitie, Paris, France. AD - Department of Cardiology, Charite-Universitatsmedizin Berlin (CBF), Hindenburgdamm 30, Berlin 12203, Germany. FAU - Laufs, Ulrich AU - Laufs U AD - Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitatsklinikum des Saarlandes, Homburg, Saar, Germany. FAU - Wiklund, Olov AU - Wiklund O AD - Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. AD - Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Stock, Jane K AU - Stock JK AD - European Atherosclerosis Society, Gothenburg, Sweden. FAU - Chapman, M John AU - Chapman MJ AD - INSERM, Dyslipidemia and Atherosclerosis Research, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy. LA - eng PT - Journal Article PT - Review PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipoproteins, LDL) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Anticholesteremic Agents/therapeutic use MH - Atherosclerosis/*etiology/prevention & control MH - Cholesterol, HDL/metabolism MH - Cholesterol, LDL/metabolism MH - Consensus MH - Epidemiologic Methods MH - Ezetimibe/therapeutic use MH - Genetic Predisposition to Disease/genetics MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hyperlipidemias/prevention & control MH - Lipoproteins, LDL/*physiology MH - Proprotein Convertase 9/antagonists & inhibitors PMC - PMC5837225 OTO - NOTNLM OT - Atherosclerosis OT - Cardiovascular disease OT - Causality OT - Clinical trials OT - Ezetimibe OT - Low-density lipoprotein OT - Mendelian randomization OT - PCSK9 OT - Recommendations OT - Statin EDAT- 2017/04/27 06:00 MHDA- 2018/07/18 06:00 CRDT- 2017/04/27 06:00 PHST- 2016/11/30 00:00 [received] PHST- 2017/03/08 00:00 [accepted] PHST- 2017/04/27 06:00 [pubmed] PHST- 2018/07/18 06:00 [medline] PHST- 2017/04/27 06:00 [entrez] AID - 3745109 [pii] AID - 10.1093/eurheartj/ehx144 [doi] PST - ppublish SO - Eur Heart J. 2017 Aug 21;38(32):2459-2472. doi: 10.1093/eurheartj/ehx144. PMID- 28741244 OWN - NLM STAT- MEDLINE DCOM- 20180629 LR - 20181202 IS - 1573-7241 (Electronic) IS - 0920-3206 (Linking) VI - 31 IP - 4 DP - 2017 Aug TI - Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins: a Systematic Review and Meta-Analysis. PG - 419-431 LID - 10.1007/s10557-017-6743-0 [doi] AB - PURPOSE: We conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing of statins. METHODS: We searched selected databases through January 2, 2017 to identify relevant RCTs and quasi-RCTs. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), while secondary outcomes included adverse events and adherence. RESULTS: Twelve RCTs and 1 quasi-RCT (n = 1023 patients) were included in the analysis. Pooled analysis revealed no statistically significant difference between alternate-day and daily regimens of atorvastatin and rosuvastatin in terms of change in LDL-C (mean difference [MD] 6.79 mg/dL, 95% confidence interval [CI] -1.59, 15.17, p = 0.11, and 10.51 mg/dL, 95%CI -0.23, 21.26, p = 0.06, respectively) and TG (p > 0.05). Daily regimens of atorvastatin and rosuvastatin were superior to alternate-day regimes in term of change in TC (MD 12.45 mg/L, 95%CI 8.14, 16.76, p < 0.00001, and 15.80 mg/dL, 95%CI 5.66, 25.95, p = 0.002, respectively). For all outcomes, there was no statistically significant difference between alternate-day and daily regimens for both fluvastatin and pravastatin (p > 0.05). Both regimens of statins were generally well tolerated with good adherence. CONCLUSIONS: Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG. FAU - Awad, Kamal AU - Awad K AUID- ORCID: http://orcid.org/0000-0001-6707-1629 AD - Faculty of Medicine, Zagazig University, El-Sharkia, Zagazig, 44519, Egypt. kamal225244@medicine.zu.edu.eg. FAU - Mikhailidis, Dimitri P AU - Mikhailidis DP AD - Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK. FAU - Toth, Peter P AU - Toth PP AD - Preventive Cardiology, CGH Medical Center, Sterling, IL, USA. AD - The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. FAU - Jones, Steven R AU - Jones SR AD - The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. FAU - Moriarty, Patrick AU - Moriarty P AD - Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, KS, USA. AD - Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA. FAU - Lip, Gregory Y H AU - Lip GYH AD - University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK. FAU - Muntner, Paul AU - Muntner P AD - Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. AD - IRCCS Multimedica, Milan, Italy. FAU - Pencina, Michael J AU - Pencina MJ AD - Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Chapel Hill, NC, USA. FAU - Rosenson, Robert S AU - Rosenson RS AD - Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Rysz, Jacek AU - Rysz J AD - Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Lodz, Poland. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Lodz, Poland. AD - Polish Mother's Memorial Hospital Research Institute, Lodz, Poland. AD - Cardiovascular Research Centre, University in Zielona Gora, Zielona Gora, Poland. CN - Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cholesterol/blood MH - Cholesterol, LDL/blood MH - Drug Administration Schedule MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage/adverse effects MH - *Medication Adherence MH - Randomized Controlled Trials as Topic MH - Triglycerides/blood OTO - NOTNLM OT - Cholesterol OT - LDL cholesterol OT - Lipids OT - Lipoproteins OT - Statins EDAT- 2017/07/26 06:00 MHDA- 2018/06/30 06:00 CRDT- 2017/07/26 06:00 PHST- 2017/07/26 06:00 [pubmed] PHST- 2018/06/30 06:00 [medline] PHST- 2017/07/26 06:00 [entrez] AID - 10.1007/s10557-017-6743-0 [doi] AID - 10.1007/s10557-017-6743-0 [pii] PST - ppublish SO - Cardiovasc Drugs Ther. 2017 Aug;31(4):419-431. doi: 10.1007/s10557-017-6743-0. PMID- 27789571 OWN - NLM STAT- In-Data-Review LR - 20170816 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 38 IP - 29 DP - 2017 Aug 1 TI - European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. PG - 2245-2255 LID - 10.1093/eurheartj/ehw480 [doi] FAU - Landmesser, Ulf AU - Landmesser U AD - Department of Cardiology, Charite-Universitatsmedizin Berlin (CBF), Hindenburgdamm 30, 12203 Berlin, Berlin Institute of Health (BIH), and Deutsches Zentrum fur Herz-Kreislaufforschung (DZHK), Germany. FAU - Chapman, M. John AU - Chapman MJ AD - National Institute for Health and Medical Research (INSERM), University of Pierre and Marie Curie, Pitie-Salpetriere Hospital, 47 Hopital boulevard, Paris, 75013 France. FAU - Farnier, Michel AU - Farnier M AD - Lipid Clinic, Point Medical, Dijon, France. FAU - Gencer, Baris AU - Gencer B AD - Cardiology Division, Department of Specialties in Medicine, Geneva University Hospitals, 4, rue Gabrielle-Perret-GentilCH - 1211 Geneva, Switzerland. FAU - Gielen, Stephan AU - Gielen S AD - Department of Internal Medicine III, Martin-Luther-University Halle/Wittenberg, University Hospital, Dept. of Int. Medicine III, Universitatsring 19/2006108, Halle/Saale, Germany. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. FAU - Luscher, Thomas F AU - Luscher TF AD - University Heart Center, Cardiology Clinic, University Hospital Zurich, Ramistrasse 100, 8091 Zurich and Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. FAU - Sinning, David AU - Sinning D AD - Department of Cardiology, Charite-Universitatsmedizin Berlin (CBF), Hindenburgdamm 30, 12203 Berlin, Berlin Institute of Health (BIH), and Deutsches Zentrum fur Herz-Kreislaufforschung (DZHK), Germany. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Hacettepe University, Faculty of Medicine, Sihhiye, Ankara, Turkey. FAU - Wiklund, Olov AU - Wiklund O AD - Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. FAU - Zamorano, Jose Luis AU - Zamorano JL AD - Department of Cardiology, University Hospital Ramon y Cajal, Colmenar Viejo Road, Km. 9.1, Madrid, Spain. FAU - Pinto, Fausto J AU - Pinto FJ AD - Cardiology Department, CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Alameda da Universidade, Lisboa, Portugal. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan and Multimedica IRCSS Milano, Milan, Italy. CN - European Society of Cardiology (ESC) CN - European Atherosclerosis Society (EAS) LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 EIN - Eur Heart J. 2017 Jan 21;:. PMID: 28110294 EDAT- 2016/10/30 06:00 MHDA- 2016/10/30 06:00 CRDT- 2016/10/30 06:00 PHST- 2016/05/04 00:00 [received] PHST- 2016/08/15 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2016/10/30 06:00 [medline] PHST- 2016/10/30 06:00 [entrez] AID - ehw480 [pii] AID - 10.1093/eurheartj/ehw480 [doi] PST - ppublish SO - Eur Heart J. 2017 Aug 1;38(29):2245-2255. doi: 10.1093/eurheartj/ehw480. PMID- 28716185 OWN - NLM STAT- MEDLINE DCOM- 20180424 LR - 20180424 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 27 DP - 2017 Jul TI - Pitavastatin and HDL: Effects on plasma levels and function(s). PG - e1-e9 LID - S1567-5688(17)30043-0 [pii] LID - 10.1016/j.atherosclerosissup.2017.05.001 [doi] AB - Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported. Despite the established inverse correlation between HDL-C levels and cardiovascular risk, several clinical trials with HDL-C-increasing drugs (such as niacin, CETP inhibitors or fibrate) failed to demonstrate that a significant rise in HDL-C levels translate into a cardiovascular benefit. Statins, that are the most used lipid-lowering drugs, can also increase HDL-C levels, although this effect is highly variable among studies and statins; the most recent developed statin, pitavastatin, beside its role as LDL-C-lowering agent, increases HDL-C levels at a significantly higher extent and progressively upon treatment; such increase was observed also when patients where shifted from another statin to pitavastatin. The stratification by baseline HDL-C levels revealed that only pitavastatin significantly increased HDL-C levels in patients with baseline HDL-C /=1000 subjects followed-up for >/=1 year. Two review authors assessed study eligibility and risk of bias and undertook data extraction independently. Pooled estimates were calculated by a random-effects model and between-study heterogeneity was tested and measured by I(2) index. Furthermore, stratified analyses and the evaluation of publication bias were performed. Finally, the meta-analysis included 20 studies, 18 cohort and 2 case-control studies. Overall, NOD risk was higher in statin users than nonusers (RR 1.44; 95% CI 1.31-1.58). High between-study heterogeneity (I(2) = 97%) was found. Estimates for all single statins showed a class effect, from rosuvastatin (RR 1.61; 1.30-1.98) to simvastatin (RR 1.38; 1.19-1.61). CONCLUSIONS: The present meta-analysis confirms and reinforces the evidence of a diabetogenic effect by statins utilization. These observations confirm the need of a rigorous monitoring of patients taking statins, in particular pre-diabetic patients or patients presenting with established risk factors for diabetes. CI - Copyright (c) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Casula, M AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. Electronic address: sefap@unimi.it. FAU - Mozzanica, F AU - Mozzanica F AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Scotti, L AU - Scotti L AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Tragni, E AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Pirillo, A AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Via M. Gorki 50, Cinisello Balsamo, 20092, Milan, Italy. FAU - Corrao, G AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Catapano, A L AU - Catapano AL AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica, Via Milanese 300, 20099, Sesto S. Giovanni (MI), Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20170310 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipids) SB - IM MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Diabetes Mellitus/blood/*chemically induced/diagnosis MH - Dyslipidemias/blood/diagnosis/*drug therapy MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Lipids/blood MH - Observational Studies as Topic MH - Odds Ratio MH - Risk Assessment MH - Risk Factors OTO - NOTNLM OT - Incident diabetes OT - Meta-analysis OT - Observational studies OT - Statins EDAT- 2017/04/19 06:00 MHDA- 2017/09/07 06:00 CRDT- 2017/04/19 06:00 PHST- 2016/11/08 00:00 [received] PHST- 2017/01/11 00:00 [revised] PHST- 2017/03/02 00:00 [accepted] PHST- 2017/04/19 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/04/19 06:00 [entrez] AID - S0939-4753(17)30043-1 [pii] AID - 10.1016/j.numecd.2017.03.001 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2017 May;27(5):396-406. doi: 10.1016/j.numecd.2017.03.001. Epub 2017 Mar 10. PMID- 28237179 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20170906 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 27 IP - 5 DP - 2017 May TI - Translating the biology of adipokines in atherosclerosis and cardiovascular diseases: Gaps and open questions. PG - 379-395 LID - S0939-4753(16)30350-7 [pii] LID - 10.1016/j.numecd.2016.12.005 [doi] AB - AIM: Critically discuss the available data, to identify the current gaps and to provide key concepts that will help clinicians in translating the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases. DATA SYNTHESIS: Adipose tissue is nowadays recognized as an active endocrine organ, a function related to the ability to secrete adipokines (such as leptin and adiponectin) and pro-inflammatory cytokines (tumor necrosis factor alpha and resistin). Studies in vitro and in animal models have observed that obesity status presents a chronic low-grade inflammation as the consequence of the immune cells infiltrating the adipose tissue as well as adipocytes. This inflammatory signature is often related to the presence of cardiovascular diseases, including atherosclerosis and thrombosis. These links are less clear in humans, where the role of adipokines as prognostic marker and/or player in cardiovascular diseases is not as clear as that observed in experimental models. Moreover, plasma adipokine levels might reflect a condition of adipokine-resistance in which adipokine redundancy occurs. The investigation of the cardio-metabolic phenotype of carriers of single nucleotide polymorphisms affecting the levels or function of a specific adipokine might help determine their relevance in humans. Thus, the aim of the present review is to critically discuss the available data, identify the current gaps and provide key concepts that will help clinicians translate the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases. CI - Copyright (c) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Ruscica, M AU - Ruscica M AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Baragetti, A AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS Multimedica Hospital, Sesto San Giovanni, Milan, Italy. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia. Electronic address: danilo.norata@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20161223 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Adipokines) RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Receptors, Adipokine) SB - IM MH - Adipokines/*blood/genetics MH - Adipose Tissue/*metabolism/physiopathology MH - Animals MH - Atherosclerosis/*blood/diagnosis/physiopathology MH - Biomarkers/blood MH - Cardiovascular Diseases/*blood/diagnosis/physiopathology MH - Cytokines/blood MH - Genetic Predisposition to Disease MH - Genetic Variation MH - Humans MH - Inflammation Mediators/blood MH - Phenotype MH - Prognosis MH - Receptors, Adipokine/metabolism MH - Risk Factors MH - Signal Transduction MH - *Translational Medical Research OTO - NOTNLM OT - Adipokines OT - Atherosclerosis OT - Cardiovascular risk EDAT- 2017/02/27 06:00 MHDA- 2017/09/07 06:00 CRDT- 2017/02/27 06:00 PHST- 2016/11/05 00:00 [received] PHST- 2016/12/14 00:00 [revised] PHST- 2016/12/16 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/02/27 06:00 [entrez] AID - S0939-4753(16)30350-7 [pii] AID - 10.1016/j.numecd.2016.12.005 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2017 May;27(5):379-395. doi: 10.1016/j.numecd.2016.12.005. Epub 2016 Dec 23. PMID- 28304229 OWN - NLM STAT- MEDLINE DCOM- 20170421 LR - 20181202 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 376 IP - 16 DP - 2017 Apr 20 TI - Antidrug Antibodies in Patients Treated with Alirocumab. PG - 1589-90 LID - 10.1056/NEJMc1616623 [doi] FAU - Roth, Eli M AU - Roth EM AD - Sterling Research Group, Cincinnati, OH eroth@sterlingresearch.org. FAU - Goldberg, Anne C AU - Goldberg AC AD - Washington University School of Medicine, St. Louis, MO. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan Multimedica IRCCS, Milan, Italy. FAU - Torri, Albert AU - Torri A AD - Regeneron Pharmaceuticals, Tarrytown, NY. FAU - Yancopoulos, George D AU - Yancopoulos GD AD - Regeneron Pharmaceuticals, Tarrytown, NY. FAU - Stahl, Neil AU - Stahl N AD - Regeneron Pharmaceuticals, Tarrytown, NY. FAU - Brunet, Aurelie AU - Brunet A AD - Sanofi, Bridgewater, NJ. FAU - Lecorps, Guillaume AU - Lecorps G AD - Sanofi, Chilly Mazarin, France. FAU - Colhoun, Helen M AU - Colhoun HM AD - University of Edinburgh, Edinburgh, United Kingdom. LA - eng PT - Letter PT - Comment DEP - 20170317 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Antibodies) RN - 0 (Antibodies, Monoclonal) RN - 0 (Anticholesteremic Agents) SB - AIM SB - IM CON - N Engl J Med. 2017 Apr 20;376(16):1517-1526. PMID: 28304227 MH - Antibodies MH - *Antibodies, Monoclonal MH - *Anticholesteremic Agents MH - Humans EDAT- 2017/03/18 06:00 MHDA- 2017/04/22 06:00 CRDT- 2017/03/18 06:00 PHST- 2017/03/18 06:00 [pubmed] PHST- 2017/04/22 06:00 [medline] PHST- 2017/03/18 06:00 [entrez] AID - 10.1056/NEJMc1616623 [doi] PST - ppublish SO - N Engl J Med. 2017 Apr 20;376(16):1589-90. doi: 10.1056/NEJMc1616623. Epub 2017 Mar 17. PMID- 28407816 OWN - NLM STAT- MEDLINE DCOM- 20180302 LR - 20181113 IS - 1472-6947 (Electronic) IS - 1472-6947 (Linking) VI - 17 IP - 1 DP - 2017 Apr 13 TI - Automatic identification of variables in epidemiological datasets using logic regression. PG - 40 LID - 10.1186/s12911-017-0429-1 [doi] AB - BACKGROUND: For an individual participant data (IPD) meta-analysis, multiple datasets must be transformed in a consistent format, e.g. using uniform variable names. When large numbers of datasets have to be processed, this can be a time-consuming and error-prone task. Automated or semi-automated identification of variables can help to reduce the workload and improve the data quality. For semi-automation high sensitivity in the recognition of matching variables is particularly important, because it allows creating software which for a target variable presents a choice of source variables, from which a user can choose the matching one, with only low risk of having missed a correct source variable. METHODS: For each variable in a set of target variables, a number of simple rules were manually created. With logic regression, an optimal Boolean combination of these rules was searched for every target variable, using a random subset of a large database of epidemiological and clinical cohort data (construction subset). In a second subset of this database (validation subset), this optimal combination rules were validated. RESULTS: In the construction sample, 41 target variables were allocated on average with a positive predictive value (PPV) of 34%, and a negative predictive value (NPV) of 95%. In the validation sample, PPV was 33%, whereas NPV remained at 94%. In the construction sample, PPV was 50% or less in 63% of all variables, in the validation sample in 71% of all variables. CONCLUSIONS: We demonstrated that the application of logic regression in a complex data management task in large epidemiological IPD meta-analyses is feasible. However, the performance of the algorithm is poor, which may require backup strategies. FAU - Lorenz, Matthias W AU - Lorenz MW AD - Department of Neurology, University Clinic Frankfurt, Schleusenweg 2-16, D-60528, Frankfurt/Main, Germany. Matthias.lorenz@em.uni-frankfurt.de. FAU - Abdi, Negin Ashtiani AU - Abdi NA AD - Faculty of Computer Science and Engineering, Frankfurt University of Applied Sciences, Frankfurt/Main, Germany. FAU - Scheckenbach, Frank AU - Scheckenbach F AD - Department of Neurology, University Clinic Frankfurt, Schleusenweg 2-16, D-60528, Frankfurt/Main, Germany. FAU - Pflug, Anja AU - Pflug A AD - Department of Neurology, University Clinic Frankfurt, Schleusenweg 2-16, D-60528, Frankfurt/Main, Germany. FAU - Bulbul, Alpaslan AU - Bulbul A AD - Department of Neurology, University Clinic Frankfurt, Schleusenweg 2-16, D-60528, Frankfurt/Main, Germany. FAU - Catapano, Alberico L AU - Catapano AL AD - IRCSS Multimedica, Milan, Italy. AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Agewall, Stefan AU - Agewall S AD - Institute of Clinical Sciences, University of Oslo, Oslo, Norway. AD - Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway. FAU - Ezhov, Marat AU - Ezhov M AD - Atherosclerosis Department, Cardiology Research Center, Moscow, Russia. FAU - Bots, Michiel L AU - Bots ML AD - University Medical Center Utrecht, Utrecht, The Netherlands. AD - Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. FAU - Orth, Andreas AU - Orth A AD - Faculty of Computer Science and Engineering, Frankfurt University of Applied Sciences, Frankfurt/Main, Germany. CN - PROG-IMT study group LA - eng GR - U01 HL080295/HL/NHLBI NIH HHS/United States GR - R01 DE013094/DE/NIDCR NIH HHS/United States GR - N01 HC015103/HC/NHLBI NIH HHS/United States GR - N01HC55222/HL/NHLBI NIH HHS/United States GR - N01HC85086/HL/NHLBI NIH HHS/United States GR - R37 NS029993/NS/NINDS NIH HHS/United States GR - N01HC85079/HL/NHLBI NIH HHS/United States GR - N01 HC035129/HC/NHLBI NIH HHS/United States PT - Journal Article DEP - 20170413 PL - England TA - BMC Med Inform Decis Mak JT - BMC medical informatics and decision making JID - 101088682 SB - IM MH - Algorithms MH - Carotid Artery Diseases/*diagnostic imaging MH - Carotid Intima-Media Thickness MH - Data Mining MH - *Databases, Factual MH - *Epidemiologic Factors MH - Humans MH - *Logistic Models MH - *Medical Informatics Applications MH - Meta-Analysis as Topic MH - Predictive Value of Tests MH - Prognosis PMC - PMC5390441 OTO - NOTNLM OT - Data management OT - Epidemiology OT - Logic regression OT - Meta-analysis IR - Norata GD FIR - Norata, Giuseppe D IR - Empana JP FIR - Empana, Jean Philippe IR - Lin HJ FIR - Lin, Hung-Ju IR - McLachlan S FIR - McLachlan, Stela IR - Bokemark L FIR - Bokemark, Lena IR - Ronkainen K FIR - Ronkainen, Kimmo IR - Amato M FIR - Amato, Mauro IR - Schminke U FIR - Schminke, Ulf IR - Srinivasan SR FIR - Srinivasan, Sathanur R IR - Lind L FIR - Lind, Lars IR - Kato A FIR - Kato, Akihiko IR - Dimitriadis C FIR - Dimitriadis, Chrystosomos IR - Przewlocki T FIR - Przewlocki, Tadeusz IR - Okazaki S FIR - Okazaki, Shuhei IR - Stehouwer CD FIR - Stehouwer, C D A IR - Lazarevic T FIR - Lazarevic, Tatjana IR - Willeit P FIR - Willeit, Peter IR - Yanez DN FIR - Yanez, David N IR - Steinmetz H FIR - Steinmetz, Helmuth IR - Sander D FIR - Sander, Dirk IR - Poppert H FIR - Poppert, Holger IR - Desvarieux M FIR - Desvarieux, Moise IR - Ikram MA FIR - Ikram, M Arfan IR - Bevc S FIR - Bevc, Sebastjan IR - Staub D FIR - Staub, Daniel IR - Sirtori CR FIR - Sirtori, Cesare R IR - Iglseder B FIR - Iglseder, Bernhard IR - Engstrom G FIR - Engstrom, Gunnar IR - Tripepi G FIR - Tripepi, Giovanni IR - Beloqui O FIR - Beloqui, Oscar IR - Lee MS FIR - Lee, Moo-Sik IR - Friera A FIR - Friera, Alfonsa IR - Xie W FIR - Xie, Wuxiang IR - Grigore L FIR - Grigore, Liliana IR - Plichart M FIR - Plichart, Matthieu IR - Su TC FIR - Su, Ta-Chen IR - Robertson C FIR - Robertson, Christine IR - Schmidt C FIR - Schmidt, Caroline IR - Tuomainen TP FIR - Tuomainen, Tomi-Pekka IR - Veglia F FIR - Veglia, Fabrizio IR - Volzke H FIR - Volzke, Henry IR - Nijpels G FIR - Nijpels, Giel IR - Jovanovic A FIR - Jovanovic, Aleksandar IR - Willeit J FIR - Willeit, Johann IR - Sacco RL FIR - Sacco, Ralph L IR - Franco OH FIR - Franco, Oscar H IR - Hojs R FIR - Hojs, Radovan IR - Uthoff H FIR - Uthoff, Heiko IR - Hedblad B FIR - Hedblad, Bo IR - Park HW FIR - Park, Hyun Woong IR - Suarez C FIR - Suarez, Carmen IR - Zhao D FIR - Zhao, Dong IR - Catapano A FIR - Catapano, Alberico IR - Ducimetiere P FIR - Ducimetiere, Pierre IR - Chien KL FIR - Chien, Kuo-Liong IR - Price JF FIR - Price, Jackie F IR - Bergstrom G FIR - Bergstrom, Goran IR - Kauhanen J FIR - Kauhanen, Jussi IR - Tremoli E FIR - Tremoli, Elena IR - Dorr M FIR - Dorr, Marcus IR - Berenson G FIR - Berenson, Gerald IR - Papagianni A FIR - Papagianni, Aikaterini IR - Kablak-Ziembicka A FIR - Kablak-Ziembicka, Anna IR - Kitagawa K FIR - Kitagawa, Kazuo IR - Dekker JM FIR - Dekker, Jaqueline M IR - Stolic R FIR - Stolic, Radojica IR - Kiechl S FIR - Kiechl, Stefan IR - Polak JF FIR - Polak, Joseph F IR - Sitzer M FIR - Sitzer, Matthias IR - Bickel H FIR - Bickel, Horst IR - Rundek T FIR - Rundek, Tatjana IR - Hofman A FIR - Hofman, Albert IR - Ekart R FIR - Ekart, Robert IR - Frauchiger B FIR - Frauchiger, Beat IR - Castelnuovo S FIR - Castelnuovo, Samuela IR - Rosvall M FIR - Rosvall, Maria IR - Zoccali C FIR - Zoccali, Carmine IR - Landecho MF FIR - Landecho, Manuel F IR - Bae JH FIR - Bae, Jang-Ho IR - Gabriel R FIR - Gabriel, Rafael IR - Liu J FIR - Liu, Jing IR - Baldassarre D FIR - Baldassarre, Damiano IR - Kavousi M FIR - Kavousi, Maryam EDAT- 2017/04/15 06:00 MHDA- 2018/03/03 06:00 CRDT- 2017/04/15 06:00 PHST- 2016/05/12 00:00 [received] PHST- 2017/03/23 00:00 [accepted] PHST- 2017/04/15 06:00 [entrez] PHST- 2017/04/15 06:00 [pubmed] PHST- 2018/03/03 06:00 [medline] AID - 10.1186/s12911-017-0429-1 [doi] AID - 10.1186/s12911-017-0429-1 [pii] PST - epublish SO - BMC Med Inform Decis Mak. 2017 Apr 13;17(1):40. doi: 10.1186/s12911-017-0429-1. PMID- 28374849 OWN - NLM STAT- In-Process LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 DP - 2017 Apr 4 TI - Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials. PG - 45788 LID - 10.1038/srep45788 [doi] AB - Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40-80 mg, rosuvastatin 20-40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20-<40 mg, rosuvastatin 10-<20 mg, simvastatin 40-<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita di Milano and IRCCS Multimedica, Milan, Italy. FAU - Lee, L Veronica AU - Lee LV AD - Sanofi, Bridgewater, New Jersey, USA. FAU - Louie, Michael J AU - Louie MJ AD - Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA. FAU - Thompson, Desmond AU - Thompson D AD - Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA. FAU - Bergeron, Jean AU - Bergeron J AD - Clinique des Maladies Lipidiques, CHU de Quebec-Universite Laval, Quebec, QC, Canada. FAU - Krempf, Michel AU - Krempf M AD - CHU de Nantes - Hopital Nord Laennec, Saint-Herblain, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170404 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 PMC - PMC5379546 EDAT- 2017/04/05 06:00 MHDA- 2017/04/05 06:00 CRDT- 2017/04/05 06:00 PHST- 2017/01/27 00:00 [received] PHST- 2017/03/01 00:00 [accepted] PHST- 2017/04/05 06:00 [entrez] PHST- 2017/04/05 06:00 [pubmed] PHST- 2017/04/05 06:00 [medline] AID - srep45788 [pii] AID - 10.1038/srep45788 [doi] PST - epublish SO - Sci Rep. 2017 Apr 4;7:45788. doi: 10.1038/srep45788. PMID- 28434484 OWN - NLM STAT- MEDLINE DCOM- 20180314 LR - 20180314 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 26 DP - 2017 Apr TI - Practical aspects in the management of statin-associated muscle symptoms (SAMS). PG - 45-55 LID - S1567-5688(17)30024-7 [pii] LID - 10.1016/S1567-5688(17)30024-7 [doi] AB - BACKGROUND AND AIMS: Statin-associated muscle symptoms (SAMS) frequently cause statin non-adherence, switching and discontinuation, contributing to adverse cardiovascular (CV) outcomes. Therefore, the management of SAMS is key in the effective treatment of patients with cardiovascular disease (CVD), through achievement of maximum-tolerated statin dosing and other practical aspects. The aim of this article is to provide practical, focused advice for healthcare professionals on the management of patients with SAMS. METHODS: An expert working group combined current evidence, published guidelines and experiences surrounding a number of topics concerning SAMS to provide recommendations on how to best assess and manage this condition and reach the highest tolerated dose of statin for each individual patient. RESULTS: The group collaborated to provide guidance on definitions in the SAMS field, psychological issues, re-challenging and switching treatments, as well as interpretation of current guidelines and optimal treatment of SAMS in different patient populations. An algorithm was developed to guide the management of patients with SAMS. In addition, the expert working group considered some of the more complex scenarios in a series of frequently asked questions and suggested answers. CONCLUSIONS: The expert working group gave recommendations for healthcare professionals on the management of SAMS but highlighted the importance of tailoring the treatment approach to each individual patient. Evidence supporting the role of nutraceuticals and complementary therapies, such as vitamin D, was lacking, however the majority of the group favoured combination therapy with ezetimibe and the addition of PCSK9 inhibitors in high-risk patients. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Laufs, Ulrich AU - Laufs U AD - Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany. Electronic address: Ulrich.Laufs@uniklinikum-saarland.de. FAU - Filipiak, Krysztof J AU - Filipiak KJ AD - First Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. FAU - Gouni-Berthold, Ioanna AU - Gouni-Berthold I AD - Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, and IRCCS Multimedica, Milan, Italy. CN - SAMS expert working group LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Cardiovascular Diseases/*drug therapy MH - *Disease Management MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/therapeutic use MH - Muscular Diseases/chemically induced/*prevention & control MH - *Practice Guidelines as Topic OTO - NOTNLM OT - Cardiovascular disease OT - Cholesterol OT - Lipids OT - Muscle symptoms OT - Myalgia OT - Myopathy OT - Statin OT - Statin intolerance IR - Mandraffino G FIR - Mandraffino, Giuseppe IRAD- Universita degli Studi di Messina, Italy. IR - Benlian P FIR - Benlian, Pascale IRAD- Universite Lille 2, France. EDAT- 2017/04/25 06:00 MHDA- 2018/03/15 06:00 CRDT- 2017/04/25 06:00 PHST- 2017/04/25 06:00 [entrez] PHST- 2017/04/25 06:00 [pubmed] PHST- 2018/03/15 06:00 [medline] AID - S1567-5688(17)30024-7 [pii] AID - 10.1016/S1567-5688(17)30024-7 [doi] PST - ppublish SO - Atheroscler Suppl. 2017 Apr;26:45-55. doi: 10.1016/S1567-5688(17)30024-7. PMID- 28529917 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20181113 IS - 2223-3652 (Print) IS - 2223-3652 (Linking) VI - 7 IP - Suppl 1 DP - 2017 Apr TI - Current guidelines on prevention with a focus on dyslipidemias. PG - S4-S10 LID - 10.21037/cdt.2017.04.04 [doi] AB - Examination of the current the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on the prevention of cardiovascular disease and the management of dyslipidemias finds much common ground. Both note that Atherosclerotic cardiovascular disease (ASCVD) is, in most people, the product of a number of risk factors, notably tobacco exposure, hyperlipidemia, hypertension, inactivity, overweight and diabetes. They stress that risk calculators can help in the assessment of risk in apparently healthy persons. Persons with established ASCVD and many with diabetes or renal impairment are at high to very high risk and warrant intensive risk factor advice and guideline-based preventive therapies. The ACC/AHA guidelines favor the universal use of statins in all high-risk subjects and in primary prevention where the global risk exceeds 7.5% in 10 years, with a percentage reduction in low-density lipoprotein cholesterol (LDL-C) based on statin intensity as the "goal". In contrast, the ESC/EAS guidelines favor a goal or percentage-based reduction in LDL-C based on total risk and baseline LDL-C level. Both guidelines consider certain imaging and other measures to stratify risk as well as the use of non-statin therapies in those not achieving recommended targets. Perhaps the most important challenges are to stress similarities rather than differences, and to simplify communications with both healthcare professionals and the public. FAU - Graham, Ian M AU - Graham IM AD - Trinity College Dublin, Dublin, Ireland. AD - Adelaide Health Foundation, Tallaght Hospital, Dublin, Ireland. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular sciences and IRCCS Multimedica, University of Milan, Milan, Italy. FAU - Wong, Nathan D AU - Wong ND AD - Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, USA. LA - eng PT - Journal Article PT - Review PL - China (Republic : 1949- ) TA - Cardiovasc Diagn Ther JT - Cardiovascular diagnosis and therapy JID - 101601613 PMC - PMC5418212 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease (ASCVD) OT - cardiovascular risk OT - cholesterol OT - low-density lipoprotein cholesterol (LDL-C) OT - risk factors COIS- Conflicts of Interest: IM Graham has received speaker fees confined to talks on the content of the guidelines and on risk estimation from MSD and Pfizer. AL Catapano has received speaker/consulting fees from Aegerion, Abbot, Amgen, BMS, Eli Lilly, Genzyme, Kowa, Merck, Novartis, Pfizer, Recordati, Roche, Sanofi and Sigma-Tau. ND Wong has received research support thorough his institution from Amgen, Regneron and Gilead, and speaker/consulting fees from Amgen, Merck, Pfizer, Sanofi and Regeneron. EDAT- 2017/05/23 06:00 MHDA- 2017/05/23 06:01 CRDT- 2017/05/23 06:00 PHST- 2017/05/23 06:00 [entrez] PHST- 2017/05/23 06:00 [pubmed] PHST- 2017/05/23 06:01 [medline] AID - 10.21037/cdt.2017.04.04 [doi] AID - cdt-07-S1-S4 [pii] PST - ppublish SO - Cardiovasc Diagn Ther. 2017 Apr;7(Suppl 1):S4-S10. doi: 10.21037/cdt.2017.04.04. PMID- 28466399 OWN - NLM STAT- MEDLINE DCOM- 20180105 LR - 20181113 IS - 1573-7241 (Electronic) IS - 0920-3206 (Linking) VI - 31 IP - 2 DP - 2017 Apr TI - Identification and Management of Statin-Associated Symptoms in Clinical Practice: Extension of a Clinician Survey to 12 Further Countries. PG - 187-195 LID - 10.1007/s10557-017-6727-0 [doi] AB - PURPOSE: Statins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. METHODS: A cross-sectional survey was conducted (2015-2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated. RESULTS: Muscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17-74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40-90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43-72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52-83%). CONCLUSIONS: The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible. FAU - Rosenson, Robert S AU - Rosenson RS AD - Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, MC1 Level, New York, NY, 10029, USA. robert.rosenson@mssm.edu. FAU - Gandra, Shravanthi R AU - Gandra SR AD - Amgen Inc., Thousand Oaks, CA, USA. FAU - McKendrick, Jan AU - McKendrick J AD - PRMA Consulting, Fleet, Hampshire, UK. FAU - Dent, Ricardo AU - Dent R AD - Amgen Inc., Thousand Oaks, CA, USA. FAU - Wieffer, Heather AU - Wieffer H AD - PRMA Consulting, Fleet, Hampshire, UK. FAU - Cheng, Lung-I AU - Cheng LI AD - Amgen Inc., Thousand Oaks, CA, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milano and IRCCS Multimedica, Milan, Italy. FAU - Oh, Paul AU - Oh P AD - Toronto Rehabilitation Institute, Toronto, ON, Canada. FAU - Kees Hovingh, G AU - Kees Hovingh G AD - Academic Medical Center, Amsterdam, the Netherlands. FAU - Stroes, Erik S AU - Stroes ES AD - Academic Medical Center, Amsterdam, the Netherlands. LA - eng PT - Journal Article PT - Multicenter Study PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Colombia/epidemiology MH - Cross-Sectional Studies MH - Dose-Response Relationship, Drug MH - Drug Substitution MH - Europe/epidemiology MH - Health Care Surveys MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*adverse effects MH - Hypercholesterolemia/diagnosis/*drug therapy/epidemiology MH - Muscle, Skeletal/*drug effects MH - Muscular Diseases/chemically induced/*diagnosis/epidemiology/*therapy MH - *Practice Patterns, Physicians' MH - Predictive Value of Tests MH - Prevalence MH - Risk Assessment MH - Risk Factors MH - Saudi Arabia/epidemiology MH - United Arab Emirates/epidemiology PMC - PMC5427112 OTO - NOTNLM OT - Clinical practice OT - Hypercholesterolemia OT - Reduced statin tolerance OT - Statin-associated muscle symptoms OT - Statin-associated symptoms EDAT- 2017/05/04 06:00 MHDA- 2018/01/06 06:00 CRDT- 2017/05/04 06:00 PHST- 2017/05/04 06:00 [pubmed] PHST- 2018/01/06 06:00 [medline] PHST- 2017/05/04 06:00 [entrez] AID - 10.1007/s10557-017-6727-0 [doi] AID - 10.1007/s10557-017-6727-0 [pii] PST - ppublish SO - Cardiovasc Drugs Ther. 2017 Apr;31(2):187-195. doi: 10.1007/s10557-017-6727-0. PMID- 28190771 OWN - NLM STAT- MEDLINE DCOM- 20170710 LR - 20181113 IS - 1932-7420 (Electronic) IS - 1550-4131 (Linking) VI - 25 IP - 3 DP - 2017 Mar 7 TI - Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4(+) T Cell Differentiation via PI3K p110delta-Akt-Mediated Signals. PG - 593-609 LID - S1550-4131(17)30043-8 [pii] LID - 10.1016/j.cmet.2017.01.008 [doi] AB - Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4(+) T cells. Memory CD4(+) T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4(+) T cell differentiation into CD44(hi)-CCR7(lo)-CD62L(lo)-CXCR3(+)-LFA1(+) effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4(+) T cells and dendritic cells and was mediated via direct exposure of CD4(+) T cells to palmitate, leading to increased activation of a PI3K p110delta-Akt-dependent pathway upon priming. CI - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Mauro, Claudio AU - Mauro C AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. Electronic address: c.mauro@qmul.ac.uk. FAU - Smith, Joanne AU - Smith J AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Cucchi, Danilo AU - Cucchi D AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK; Istituto Pasteur, Fondazione Cenci Bolognetti, Rome 00161, Italy. FAU - Coe, David AU - Coe D AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Fu, Hongmei AU - Fu H AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy. FAU - Cermenati, Gaia AU - Cermenati G AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy. FAU - Caruso, Donatella AU - Caruso D AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy. FAU - Mitro, Nico AU - Mitro N AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy; IRCCS Multimedica, Milan 2-242091, Italy. FAU - Ammirati, Enrico AU - Ammirati E AD - De Gasperis Cardio Center, Niguarda Ca' Granda Hospital, Milan 3-20162, Italy. FAU - Longhi, Maria P AU - Longhi MP AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. FAU - Okkenhaug, Klaus AU - Okkenhaug K AD - Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, CB22 3AT, UK. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan 9-20133, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia. FAU - Marelli-Berg, Federica M AU - Marelli-Berg FM AD - William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. Electronic address: f.marelli-berg@qmul.ac.uk. LA - eng GR - RG/14/2/30616/British Heart Foundation/United Kingdom GR - FS/12/38/29640/British Heart Foundation/United Kingdom GR - BBS/E/B/000C0409/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBS/E/B/000C0407/Biotechnology and Biological Sciences Research Council/United Kingdom GR - FS/13/49/30421/British Heart Foundation/United Kingdom GR - FS/11/64/28945/British Heart Foundation/United Kingdom GR - PG/15/105/31906/British Heart Foundation/United Kingdom GR - CH/15/2/32064/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170209 PL - United States TA - Cell Metab JT - Cell metabolism JID - 101233170 RN - 0 (CXCR3 protein, human) RN - 0 (Fatty Acids) RN - 0 (Receptors, CXCR3) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM CIN - Cell Metab. 2017 Mar 7;25(3):490-492. PMID: 28273470 MH - Adiposity MH - Animals MH - Antigen Presentation/immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - *Cell Differentiation MH - Cell Movement MH - Dendritic Cells/immunology MH - Diet, High-Fat MH - Fatty Acids/metabolism MH - Female MH - Humans MH - *Immunologic Memory MH - Inflammation/pathology MH - Lymphocyte Activation/immunology MH - Lymphoid Tissue/pathology MH - Male MH - Mice, Inbred C57BL MH - Obesity/enzymology/*immunology/pathology MH - Oxidation-Reduction MH - Phenotype MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Receptors, CXCR3/metabolism MH - *Signal Transduction MH - *Stress, Physiological PMC - PMC5355363 OTO - NOTNLM OT - *Akt OT - *CD4 OT - *T lymphocyte OT - *differentiation OT - *effector memory OT - *high-fat diet OT - *inflammation OT - *obesity OT - *palmitate OT - *saturated fatty acid EDAT- 2017/02/14 06:00 MHDA- 2017/07/14 06:00 CRDT- 2017/02/14 06:00 PHST- 2016/03/23 00:00 [received] PHST- 2016/09/29 00:00 [revised] PHST- 2017/01/11 00:00 [accepted] PHST- 2017/02/14 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2017/02/14 06:00 [entrez] AID - S1550-4131(17)30043-8 [pii] AID - 10.1016/j.cmet.2017.01.008 [doi] PST - ppublish SO - Cell Metab. 2017 Mar 7;25(3):593-609. doi: 10.1016/j.cmet.2017.01.008. Epub 2017 Feb 9. PMID- 27681501 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20171113 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 125 DP - 2017 Mar TI - Corrigendum to "Incretin-based drugs and risk of acute pancreatitis: A nested-case control study within a healthcare database" [Diabetes Res. Clin. Pract. 108 (2) (2015) 243-249]. PG - 68 LID - S0168-8227(16)30543-5 [pii] LID - 10.1016/j.diabres.2016.09.003 [doi] FAU - Soranna, Davide AU - Soranna D AD - Dipartimento di Statistica e Metodi Quantitativi, Sezione di Biostatistica, Epidemiologia e Sanita Pubblica, Universita Milano-Bicocca, Milan, Italy; Istituto Auxologico Italiano, Milan, Italy. FAU - Bosetti, Cristina AU - Bosetti C AD - Dipartimento di Epidemiologia, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. FAU - Casula, Manuela AU - Casula M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano, Milan, Italy; IRCSS Multimedica, Milan, Italy. FAU - La Vecchia, Carlo AU - La Vecchia C AD - Dipartimento di Scienze Cliniche e di Comunita, Universita Milano, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Unita Organizzativa Governo dei dati, delle strategie e piani del sistema sanitario, Regione Lombardia, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Dipartimento di Statistica e Metodi Quantitativi, Sezione di Biostatistica, Epidemiologia e Sanita Pubblica, Universita Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. LA - eng PT - Journal Article DEP - 20160924 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 EDAT- 2016/09/30 06:00 MHDA- 2016/09/30 06:01 CRDT- 2016/09/30 06:00 PHST- 2016/09/30 06:00 [pubmed] PHST- 2016/09/30 06:01 [medline] PHST- 2016/09/30 06:00 [entrez] AID - S0168-8227(16)30543-5 [pii] AID - 10.1016/j.diabres.2016.09.003 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2017 Mar;125:68. doi: 10.1016/j.diabres.2016.09.003. Epub 2016 Sep 24. PMID- 29389351 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20180516 IS - 1885-5857 (Electronic) IS - 1885-5857 (Linking) VI - 70 IP - 2 DP - 2017 Feb TI - 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. PG - 115 LID - S1885-5857(17)30002-6 [pii] LID - 10.1016/j.rec.2017.01.002 [doi] FAU - Catapano, Alberico L AU - Catapano AL FAU - Graham, Ian AU - Graham I FAU - De Backer, Guy AU - De Backer G FAU - Wiklund, Olov AU - Wiklund O FAU - Chapman, M John AU - Chapman MJ FAU - Drexel, Heinz AU - Drexel H FAU - Hoes, Arno W AU - Hoes AW FAU - Jennings, Catriona S AU - Jennings CS FAU - Landmesser, Ulf AU - Landmesser U FAU - Pedersen, Terje R AU - Pedersen TR FAU - Reiner, Zeljko AU - Reiner Z FAU - Riccardi, Gabriele AU - Riccardi G FAU - Taskinen, Marja-Riita AU - Taskinen MR FAU - Tokgozoglu, Lale AU - Tokgozoglu L FAU - Monique Verschuren, W M AU - Monique Verschuren WM FAU - Vlachopoulos, Charalambos AU - Vlachopoulos C FAU - Wood, David A AU - Wood DA FAU - Luis Zamorano, Jose AU - Luis Zamorano J CN - Additional Contributor FAU - Cooney, Marie-Therese AU - Cooney MT LA - eng LA - spa PT - Journal Article TT - 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. PL - Spain TA - Rev Esp Cardiol (Engl Ed) JT - Revista espanola de cardiologia (English ed.) JID - 101587954 EDAT- 2018/02/02 06:00 MHDA- 2018/02/02 06:01 CRDT- 2018/02/02 06:00 PHST- 2018/02/02 06:00 [entrez] PHST- 2018/02/02 06:00 [pubmed] PHST- 2018/02/02 06:01 [medline] AID - S1885-5857(17)30002-6 [pii] AID - 10.1016/j.rec.2017.01.002 [doi] PST - ppublish SO - Rev Esp Cardiol (Engl Ed). 2017 Feb;70(2):115. doi: 10.1016/j.rec.2017.01.002. PMID- 27634340 OWN - NLM STAT- MEDLINE DCOM- 20180221 LR - 20180323 IS - 1878-5832 (Electronic) IS - 1359-6446 (Linking) VI - 22 IP - 1 DP - 2017 Jan TI - Statin-associated myopathy and the quest for biomarkers: can we effectively predict statin-associated muscle symptoms? PG - 85-96 LID - S1359-6446(16)30321-X [pii] LID - 10.1016/j.drudis.2016.09.001 [doi] AB - Over the past three decades, statins have become the cornerstone of prevention and treatment of atherosclerotic cardiovascular and metabolic diseases. Albeit generally well tolerated, these drugs can elicit a variety of muscle-associated symptoms that represent the most important reason for treatment discontinuation. Statin-associated myopathy has been systematically underestimated by randomized controlled trials as compared with the incidence observed in clinical practice and obtained from patient registries. There are several reasons for this discrepancy, among which the lack of reliable diagnostic tests and a validated questionnaire to assess muscle symptoms are recognized as unmet needs. Here, we review the cellular and molecular mechanisms underlying statin-associated myopathy and discuss the experimental and clinical data on various biomarkers to diagnose and predict muscle-related complaints. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Muntean, Danina M AU - Muntean DM AD - Department of Pathophysiology Functional Sciences, Victor Babes University of Medicine and Pharmacy of Timisoara, Timisoara, Romania; Center for Translational Research and Systems Medicine, Victor Babes University of Medicine and Pharmacy of Timisoara, Timisoara, Romania. FAU - Thompson, Paul D AU - Thompson PD AD - Division of Cardiology, Hartford Hospital, Hartford, CT, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy. FAU - Stasiolek, Mariusz AU - Stasiolek M AD - Department of Neurology, Polish Mother's Memorial Hospital-Research Institute in Lodz, Lodz, Poland. FAU - Fabis, Jaroslaw AU - Fabis J AD - Department of Arthroscopy, Minimally Invasive Surgery and Sports Traumatology, Medical University of Lodz, Poland. FAU - Muntner, Paul AU - Muntner P AD - Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Serban, Maria-Corina AU - Serban MC AD - Department of Pathophysiology Functional Sciences, Victor Babes University of Medicine and Pharmacy of Timisoara, Timisoara, Romania; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland; Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland. Electronic address: maciejbanach@aol.co.uk. LA - eng PT - Journal Article PT - Review PT - Research Support, Non-U.S. Gov't DEP - 20160912 PL - England TA - Drug Discov Today JT - Drug discovery today JID - 9604391 RN - 0 (Biomarkers) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Animals MH - Biomarkers/*analysis MH - Drug Interactions MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/pharmacokinetics MH - Muscular Diseases/*chemically induced/*diagnosis/genetics/metabolism MH - Predictive Value of Tests MH - Risk Factors EDAT- 2016/09/17 06:00 MHDA- 2018/02/22 06:00 CRDT- 2016/09/17 06:00 PHST- 2016/05/30 00:00 [received] PHST- 2016/07/28 00:00 [revised] PHST- 2016/09/05 00:00 [accepted] PHST- 2016/09/17 06:00 [pubmed] PHST- 2018/02/22 06:00 [medline] PHST- 2016/09/17 06:00 [entrez] AID - S1359-6446(16)30321-X [pii] AID - 10.1016/j.drudis.2016.09.001 [doi] PST - ppublish SO - Drug Discov Today. 2017 Jan;22(1):85-96. doi: 10.1016/j.drudis.2016.09.001. Epub 2016 Sep 12. PMID- 27756478 OWN - NLM STAT- MEDLINE DCOM- 20170501 LR - 20171116 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 118 IP - 12 DP - 2016 Dec 15 TI - Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia. PG - 1812-1820 LID - S0002-9149(16)31478-3 [pii] LID - 10.1016/j.amjcard.2016.08.071 [doi] AB - Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG >/=126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy. CI - Copyright A(c) 2016 The Authors and Merck Sharp & Dohme Corp. Published by Elsevier Inc. All rights reserved. FAU - Toth, Peter P AU - Toth PP AD - CGH Medical Center, Sterling, Illinois; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: Peter.Toth@cghmc.com. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy. FAU - Farnier, Michel AU - Farnier M AD - Lipid Clinic, Point Medical, Dijon, France. FAU - Foody, Joanne AU - Foody J AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. FAU - Tomassini, Joanne E AU - Tomassini JE AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. FAU - Jensen, Erin AU - Jensen E AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. FAU - Polis, Adam B AU - Polis AB AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. FAU - Hanson, Mary E AU - Hanson ME AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. FAU - Musliner, Thomas A AU - Musliner TA AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. FAU - Tershakovec, Andrew M AU - Tershakovec AM AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey. LA - eng PT - Journal Article DEP - 20160913 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Anticholesteremic Agents) RN - 0 (Apolipoproteins B) RN - 0 (Blood Glucose) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Triglycerides) RN - AGG2FN16EV (Simvastatin) RN - EOR26LQQ24 (Ezetimibe) SB - AIM SB - IM MH - Aged MH - Anticholesteremic Agents/*therapeutic use MH - Apolipoproteins B/metabolism MH - Blood Glucose/*metabolism MH - Cholesterol, HDL/metabolism MH - Cholesterol, LDL/metabolism MH - Comorbidity MH - Drug Therapy, Combination MH - Ezetimibe/*therapeutic use MH - Fasting MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypercholesterolemia/*drug therapy/epidemiology/metabolism MH - Hyperglycemia/*chemically induced/metabolism MH - Male MH - Metabolic Syndrome/epidemiology/metabolism MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Simvastatin/*therapeutic use MH - Triglycerides/metabolism EDAT- 2016/10/21 06:00 MHDA- 2017/05/02 06:00 CRDT- 2016/10/21 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2016/08/23 00:00 [revised] PHST- 2016/08/23 00:00 [accepted] PHST- 2016/10/21 06:00 [pubmed] PHST- 2017/05/02 06:00 [medline] PHST- 2016/10/21 06:00 [entrez] AID - S0002-9149(16)31478-3 [pii] AID - 10.1016/j.amjcard.2016.08.071 [doi] PST - ppublish SO - Am J Cardiol. 2016 Dec 15;118(12):1812-1820. doi: 10.1016/j.amjcard.2016.08.071. Epub 2016 Sep 13. PMID- 27939304 OWN - NLM STAT- MEDLINE DCOM- 20170213 LR - 20170213 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 22 DP - 2016 Dec TI - Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. PG - 1-32 LID - S1567-5688(16)30049-6 [pii] LID - 10.1016/j.atherosclerosissup.2016.10.001 [doi] AB - BACKGROUND: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. METHODS: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. CONCLUSIONS: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. CN - EAS Familial Hypercholesterolaemia Studies Collaboration FAU - Vallejo-Vaz, Antonio J AU - Vallejo-Vaz AJ AD - Imperial Centre for Cardiovascular Disease Prevention (ICCP), School of Public Health, Imperial College London, London, UK. Electronic address: a.vallejo-vaz@imperial.ac.uk. FAU - Akram, Asif AU - Akram A AD - Global eHealth Unit, School of Public Health, Imperial College London, London, UK; Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. FAU - Kondapally Seshasai, Sreenivasa Rao AU - Kondapally Seshasai SR AD - Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, UK. FAU - Cole, Della AU - Cole D AD - Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, UK. FAU - Watts, Gerald F AU - Watts GF AD - Cardiovascular Medicine, Royal Perth Hospital, University of Western Australia, Perth, Australia. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands. FAU - Kastelein, John J P AU - Kastelein JJ AD - Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands. FAU - Mata, Pedro AU - Mata P AD - Fundacion Hipercolesterolemia Familiar, Madrid, Spain. FAU - Raal, Frederick J AU - Raal FJ AD - Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Santos, Raul D AU - Santos RD AD - Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. FAU - Soran, Handrean AU - Soran H AD - University Department of Medicine, Central Manchester University Hospitals, Manchester, UK. FAU - Freiberger, Tomas AU - Freiberger T AD - Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Ceitec, Masaryk University, Brno, Czech Republic. FAU - Abifadel, Marianne AU - Abifadel M AD - Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Saint-Joseph University, Beirut, Lebanon. FAU - Aguilar-Salinas, Carlos A AU - Aguilar-Salinas CA AD - Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico. FAU - Alnouri, Fahad AU - Alnouri F AD - Cardiovascular Prevention and Rehabilitation Unit, Prince Sultan Cardiac Centre Riyadh, Riyadh, Saudi Arabia. FAU - Alonso, Rodrigo AU - Alonso R AD - Lipid Clinic, Department of Nutrition, Clinica Las Condes, Santiago de Chile, Chile. FAU - Al-Rasadi, Khalid AU - Al-Rasadi K AD - Sultan Qaboos University Hospital, Muscat, Oman. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, Medical University of Lodz, Lodz, Poland. FAU - Bogsrud, Martin P AU - Bogsrud MP AD - National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Norway. FAU - Bourbon, Mafalda AU - Bourbon M AD - Instituto Nacional de Saude Doutor Ricardo Jorge and Biosystems & Integrative Sciences Institute (BioISI), Universidade de Lisboa, Portugal. FAU - Bruckert, Eric AU - Bruckert E AD - Endocrinologie, metabolisme et prevention cardiovasculaire, Institut E3M et IHU cardiometabolique (ICAN), Hopital Pitie-Salpetriere, Paris, France. FAU - Car, Josip AU - Car J AD - Global eHealth Unit, School of Public Health, Imperial College London, London, UK; Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. FAU - Ceska, Richard AU - Ceska R AD - Charles University in Prague, Prague, Czech Republic. FAU - Corral, Pablo AU - Corral P AD - FASTA University, School of Medicine, Mar del Plata, Argentina. FAU - Descamps, Olivier AU - Descamps O AD - Centres Hospitaliers Jolimont, Haine Saint-Paul, Belgium. FAU - Dieplinger, Hans AU - Dieplinger H AD - Austrian Atherosclerosis Society, c/o Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Do, Can T AU - Do CT AD - Vietnam Heart Institute, Bach Mai Hospital, Hanoi, Viet Nam. FAU - Durst, Ronen AU - Durst R AD - Hadassah Hebrew University Medical Centre, Jerusalem, Israel. FAU - Ezhov, Marat V AU - Ezhov MV AD - Russian Cardiology Research and Production Centre, Moscow, Russia. FAU - Fras, Zlatko AU - Fras Z AD - University Medical Centre Ljubljana, Division of Medicine, Preventive Cardiology Unit, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. FAU - Gaita, Dan AU - Gaita D AD - Universitatea de Medicina si Farmacie Victor Babes din Timisoara, Romania. FAU - Gaspar, Isabel M AU - Gaspar IM AD - Medical Genetics Department, Centro Hospitalar de Lisboa Ocidental and Genetics Laboratory, Lisbon Medical School, University of Lisbon, Portugal. FAU - Genest, Jaques AU - Genest J AD - McGill University, Montreal, Canada. FAU - Harada-Shiba, Mariko AU - Harada-Shiba M AD - National Cerebral and Cardiovascular Centre Research Institute, Osaka, Japan. FAU - Jiang, Lixin AU - Jiang L AD - National Clinical Research Centre of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Beijing, China. FAU - Kayikcioglu, Meral AU - Kayikcioglu M AD - Ege University Medical School, Department of Cardiology, Izmir, Turkey. FAU - Lam, Carolyn S P AU - Lam CS AD - National Heart Centre Singapore and Duke-National University of Singapore, Singapore. FAU - Latkovskis, Gustavs AU - Latkovskis G AD - Research Institute of Cardiology and Regenerative Therapy, Faculty of Medicine, University of Latvia, Paul Stradins Clinical University Hospital, Riga, Latvia. FAU - Laufs, Ulrich AU - Laufs U AD - Universitat des Saarlandes, Homburg, Germany. FAU - Liberopoulos, Evangelos AU - Liberopoulos E AD - University of Ioannina Medical School, Ioannina, Greece. FAU - Lin, Jie AU - Lin J AD - Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Lin, Nan AU - Lin N AD - Imperial Centre for Cardiovascular Disease Prevention (ICCP), School of Public Health, Imperial College London, London, UK. FAU - Maher, Vincent AU - Maher V AD - Tallaght Hospital, Ireland. FAU - Majano, Nelson AU - Majano N AD - Hospital Militar de Caracas, Caracas, Venezuela. FAU - Marais, A David AU - Marais AD AD - University of Cape Town and National Health Laboratory Service, South Africa. FAU - Marz, Winfried AU - Marz W AD - Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Germany. FAU - Mirrakhimov, Erkin AU - Mirrakhimov E AD - Kyrgyz State Medical Academy, Kyrgyzstan. FAU - Miserez, Andre R AU - Miserez AR AD - Diagene GmbH, Research Institute, Reinach, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland. FAU - Mitchenko, Olena AU - Mitchenko O AD - Dyslipidaemia Department, Institute of Cardiology AMS of Ukraine, Ukraine. FAU - Nawawi, Hapizah AU - Nawawi H AD - Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM) and Faculty of Medicine, Universiti Teknologi MARA, Malaysia. FAU - Nilsson, Lennart AU - Nilsson L AD - Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark. FAU - Paragh, Gyorgy AU - Paragh G AD - Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary. FAU - Petrulioniene, Zaneta AU - Petrulioniene Z AD - Vilnius University Santariskiu Hospital, Centre of Cardiology and Angiology, Vilnius, Lithuania. FAU - Pojskic, Belma AU - Pojskic B AD - Cantonal Hospital, Zenica, Bosnia and Herzegovina. FAU - Reiner, Zeljko AU - Reiner Z AD - Department for Metabolic Diseases, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Croatia. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Biotechnology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Santos, Lourdes E AU - Santos LE AD - Cardinal Santos Medical Centre, University of the Philippines - Philippine General Hospital (UP-PGH), Philippines. FAU - Schunkert, Heribert AU - Schunkert H AD - Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Deutsches Zentrum fur Herz- und Kreislauferkrankungen (DZHK), Munich Heart Alliance, Germany. FAU - Shehab, Abdullah AU - Shehab A AD - CMHS, UAE University, AlAin, United Arab Emirates. FAU - Slimane, M Naceur AU - Slimane MN AD - Research Unit on Dyslipidaemia and Atherosclerosis, Faculty of Medicine of Monastir, Tunisia. FAU - Stoll, Mario AU - Stoll M AD - Cardiovascular Genetic Laboratory, Cardiovascular Health Commission, Montevideo, Uruguay. FAU - Su, Ta-Chen AU - Su TC AD - Department of Internal Medicine and Cardiovascular Centre, National Taiwan University Hospital, Taipei, Taiwan. FAU - Susekov, Andrey AU - Susekov A AD - Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Postgraduate Education, Ministry of Health of Russian Federation, Russia. FAU - Tilney, Myra AU - Tilney M AD - Faculty of Medicine & Surgery, Medical School, Mater Dei Hospital, University of Malta, Malta. FAU - Tomlinson, Brian AU - Tomlinson B AD - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. FAU - Tselepis, Alexandros D AU - Tselepis AD AD - Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece. FAU - Vohnout, Branislav AU - Vohnout B AD - Coordination Centre for Familial Hyperlipoproteinemias, Institute of Nutrition, FOZOS, Slovak Medical University, Department of Epidemiology, School of Medicine, Comenius University, Bratislava, Slovakia. FAU - Widen, Elisabeth AU - Widen E AD - Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. FAU - Yamashita, Shizuya AU - Yamashita S AD - Rinku General Medical Centre and Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan and Multimedica IRCCS, Milan, Italy. FAU - Ray, Kausik K AU - Ray KK AD - Imperial Centre for Cardiovascular Disease Prevention (ICCP), School of Public Health, Imperial College London, London, UK. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20161207 PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 SB - IM MH - Access to Information MH - Cooperative Behavior MH - Data Mining MH - *Delivery of Health Care, Integrated/organization & administration MH - Humans MH - Hyperlipoproteinemia Type II/diagnosis/genetics/mortality/*therapy MH - Information Storage and Retrieval MH - *International Cooperation MH - Organizational Objectives MH - *Professional Practice Gaps MH - *Registries MH - *Research Design MH - Treatment Outcome OTO - NOTNLM OT - Cardiovascular disease OT - Familial Hypercholesterolaemia Studies Collaboration OT - Familial hypercholesterolaemia OT - LDL-Cholesterol OT - Registry OT - Study design EDAT- 2016/12/13 06:00 MHDA- 2017/02/14 06:00 CRDT- 2016/12/13 06:00 PHST- 2016/12/13 06:00 [pubmed] PHST- 2017/02/14 06:00 [medline] PHST- 2016/12/13 06:00 [entrez] AID - S1567-5688(16)30049-6 [pii] AID - 10.1016/j.atherosclerosissup.2016.10.001 [doi] PST - ppublish SO - Atheroscler Suppl. 2016 Dec;22:1-32. doi: 10.1016/j.atherosclerosissup.2016.10.001. Epub 2016 Dec 7. PMID- 27751505 OWN - NLM STAT- MEDLINE DCOM- 20171106 LR - 20180518 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 255 DP - 2016 Dec TI - Circulating CD14+ and CD14(high)CD16- classical monocytes are reduced in patients with signs of plaque neovascularization in the carotid artery. PG - 171-178 LID - S0021-9150(16)31407-1 [pii] LID - 10.1016/j.atherosclerosis.2016.10.004 [doi] AB - BACKGROUND AND AIMS: Monocytes are known to play a key role in the initiation and progression of atherosclerosis and contribute to plaque destabilization through the generation of signals that promote inflammation and neoangiogenesis. In humans, studies investigating the features of circulating monocytes in advanced atherosclerotic lesions are lacking. METHODS: Patients (mean age 69 years, 56% males) with intermediate asymptomatic carotid stenosis (40-70% in diameter) were evaluated for maximal stenosis in common carotid artery, carotid bulb and internal carotid artery, overall disease burden as estimated with total plaque area (TPA), greyscale and neovascularization in 244 advanced carotid plaques. Absolute counts of circulating CD14+ monocytes, of classical (CD14(high)CD16-), intermediate (CD14(high)CD16+) and non-classical (CD14(low)CD16+) monocytes and HLA-DR+ median fluorescence intensity for each subset were evaluated with flow cytometry. RESULTS: No correlation was found between monocytes and overall atherosclerotic burden, nor with high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). In contrast, plaque signs of neovascularization were associated with significantly lower counts of circulating CD14+ monocytes (297 versus 350 cells/mm(3), p = 0.039) and of classical monocytes (255 versus 310 cells/mm(3), p = 0.029). CONCLUSIONS: Neovascularized atherosclerotic lesions selectively associate with lower blood levels of CD14+ and CD14(high)CD16- monocytes independently of systemic inflammatory activity, as indicated by normal hsCRP levels. Whether the reduction of circulating CD14+ and CD14(high)CD16- monocytes is due to a potential redistribution of these cell types into active lesions remains to be explored. CI - Copyright A(c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Ammirati, Enrico AU - Ammirati E AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; De Gasperis Cardio Center, Niguarda Ca' Granda Hospital, Milan, Italy. Electronic address: ammirati.enrico@hsr.it. FAU - Moroni, Francesco AU - Moroni F AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: moroni@studenti.unisr.it. FAU - Magnoni, Marco AU - Magnoni M AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. FAU - Di Terlizzi, Simona AU - Di Terlizzi S AD - FRACTAL - Flow cytometry Resource Advanced Cytometry Technical Applications Laboratory, San Raffaele Scientific Institute, Milan, Italy. FAU - Villa, Chiara AU - Villa C AD - FRACTAL - Flow cytometry Resource Advanced Cytometry Technical Applications Laboratory, San Raffaele Scientific Institute, Milan, Italy. FAU - Sizzano, Federico AU - Sizzano F AD - Nestle Institute of Health Sciences, Biobanking & Flow Cytometry Core EPFL, Innovation Park Batiment H, Lausanne, Switzerland. FAU - Palini, Alessio AU - Palini A AD - Nestle Institute of Health Sciences, Biobanking & Flow Cytometry Core EPFL, Innovation Park Batiment H, Lausanne, Switzerland. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - Center SISA for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Tripiciano, Fernanda AU - Tripiciano F AD - Hematology and Blood Transfusion Service, San Raffaele Scientific Institute, Milan, Italy. FAU - Scotti, Isabella AU - Scotti I AD - Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS - Multimedica Hospital, Sesto San Giovanni, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Manfredi, Angelo A AU - Manfredi AA AD - Unit of Internal Medicine & Clinical Immunology, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Center SISA for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia. FAU - Camici, Paolo G AU - Camici PG AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. LA - eng PT - Journal Article PT - Video-Audio Media PT - Research Support, Non-U.S. Gov't DEP - 20161006 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Biomarkers) RN - 0 (Contrast Media) RN - 0 (IL6 protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Phospholipids) RN - 0 (Receptors, IgG) RN - 0 (contrast agent BR1) RN - 9007-41-4 (C-Reactive Protein) RN - WS7LR3I1D6 (Sulfur Hexafluoride) SB - IM CIN - Atherosclerosis. 2016 Dec;255:117-118. PMID: 27814908 MH - Aged MH - Biomarkers/blood MH - C-Reactive Protein/analysis MH - Carotid Arteries/diagnostic imaging/*pathology MH - Carotid Stenosis/*blood/diagnostic imaging/pathology MH - Contrast Media/administration & dosage MH - Female MH - Flow Cytometry MH - Humans MH - Inflammation Mediators/blood MH - Interleukin-6/analysis MH - Lipopolysaccharide Receptors/*blood MH - Male MH - Middle Aged MH - Monocytes/*metabolism MH - *Neovascularization, Pathologic MH - Phospholipids/administration & dosage MH - *Plaque, Atherosclerotic MH - Receptors, IgG/*blood MH - Severity of Illness Index MH - Sulfur Hexafluoride/administration & dosage MH - Ultrasonography, Doppler, Duplex OTO - NOTNLM OT - *Carotid atherosclerosis OT - *Classical monocytes OT - *Contrast enhanced ultrasound OT - *Monocytes subsets OT - *Plaque neovascularization EDAT- 2016/10/19 06:00 MHDA- 2017/11/07 06:00 CRDT- 2016/10/19 06:00 PHST- 2016/01/16 00:00 [received] PHST- 2016/09/16 00:00 [revised] PHST- 2016/10/04 00:00 [accepted] PHST- 2016/10/19 06:00 [pubmed] PHST- 2017/11/07 06:00 [medline] PHST- 2016/10/19 06:00 [entrez] AID - S0021-9150(16)31407-1 [pii] AID - 10.1016/j.atherosclerosis.2016.10.004 [doi] PST - ppublish SO - Atherosclerosis. 2016 Dec;255:171-178. doi: 10.1016/j.atherosclerosis.2016.10.004. Epub 2016 Oct 6. PMID- 27959767 OWN - NLM STAT- MEDLINE DCOM- 20161229 LR - 20180125 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 375 IP - 22 DP - 2016 Dec 1 TI - Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. PG - 2144-2153 AB - BACKGROUND: Pharmacologic inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) are being evaluated in clinical trials for the treatment of cardiovascular disease. The effect of lowering low-density lipoprotein (LDL) cholesterol levels by inhibiting PCSK9 on the risk of cardiovascular events or diabetes is unknown. METHODS: We used genetic scores consisting of independently inherited variants in the genes encoding PCSK9 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR; the target of statins) as instruments to randomly assign 112,772 participants from 14 studies, with 14,120 cardiovascular events and 10,635 cases of diabetes, to groups according to the number of LDL cholesterol-lowering alleles that they had inherited. We compared the effects of lower LDL cholesterol levels that were mediated by variants in PCSK9, HMGCR, or both on the risk of cardiovascular events and the risk of diabetes. RESULTS: Variants in PCSK9 and HMGCR were associated with nearly identical protective effects on the risk of cardiovascular events per decrease of 10 mg per deciliter (0.26 mmol per liter) in the LDL cholesterol level: odds ratio for cardiovascular events, 0.81 (95% confidence interval [CI], 0.74 to 0.89) for PCSK9 and 0.81 (95% CI, 0.72 to 0.90) for HMGCR. Variants in these two genes were also associated with very similar effects on the risk of diabetes: odds ratio for each 10 mg per deciliter decrease in LDL cholesterol, 1.11 (95% CI, 1.04 to 1.19) for PCSK9 and 1.13 (95% CI, 1.06 to 1.20) for HMGCR. The increased risk of diabetes was limited to persons with impaired fasting glucose levels for both scores and was lower in magnitude than the protective effect against cardiovascular events. When present together, PCSK9 and HMGCR variants had additive effects on the risk of both cardiovascular events and diabetes. CONCLUSIONS: In this study, variants in PCSK9 had approximately the same effect as variants in HMGCR on the risk of cardiovascular events and diabetes per unit decrease in the LDL cholesterol level. The effects of these variants were independent and additive. (Funded by the Medical Research Council and the National Heart, Lung, and Blood Institute.). FAU - Ference, Brian A AU - Ference BA AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Robinson, Jennifer G AU - Robinson JG AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Brook, Robert D AU - Brook RD AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Catapano, Alberico L AU - Catapano AL AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Chapman, M John AU - Chapman MJ AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Neff, David R AU - Neff DR AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Voros, Szilard AU - Voros S AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Giugliano, Robert P AU - Giugliano RP AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Davey Smith, George AU - Davey Smith G AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Fazio, Sergio AU - Fazio S AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). FAU - Sabatine, Marc S AU - Sabatine MS AD - From the Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit (B.A.F.), the Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor (R.D.B.), and Michigan State University, East Lansing (D.R.N.) - all in Michigan; the Departments of Epidemiology and Medicine, College of Public Health, University of Iowa, Iowa City (J.G.R.); the Department of Pharmacological and Biomolecular Sciences, University of Milan and MultiMedica Istituto di Ricovero e Cura a Carattere Scientifico, Milan (A.L.C.); INSERM, Pitie-Salpetriere University Hospital, Paris (M.J.C.); the Global Genomics Group, Richmond, VA (S.V.); the Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (R.P.G., M.S.S.); the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (G.D.S.); and the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (S.F.). LA - eng GR - MC_UU_12013/1/Medical Research Council/United Kingdom PT - Journal Article PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Cholesterol, LDL) RN - EC 1.1.1.- (HMGCR protein, human) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - AIM SB - IM CIN - Nat Rev Endocrinol. 2017 Feb;13(2):65. PMID: 27983735 MH - Cardiovascular Diseases/*genetics MH - Cholesterol, LDL/*blood MH - Diabetes Mellitus/*genetics MH - Female MH - *Genetic Predisposition to Disease MH - Genetic Variation MH - Humans MH - Hydroxymethylglutaryl CoA Reductases/*genetics MH - Male MH - Middle Aged MH - Proprotein Convertase 9/*genetics MH - Random Allocation MH - Risk EDAT- 2016/12/14 06:00 MHDA- 2016/12/31 06:00 CRDT- 2016/12/14 06:00 PHST- 2016/12/14 06:00 [entrez] PHST- 2016/12/14 06:00 [pubmed] PHST- 2016/12/31 06:00 [medline] AID - 10.1056/NEJMoa1604304 [doi] PST - ppublish SO - N Engl J Med. 2016 Dec 1;375(22):2144-2153. doi: 10.1056/NEJMoa1604304. PMID- 27532233 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20190327 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 223 DP - 2016 Nov 15 TI - Genetically determined telomeres shortening is associated with carotid atherosclerosis progression and increased incidence of cardiovascular events. PG - 43-45 LID - S0167-5273(16)31870-8 [pii] LID - 10.1016/j.ijcard.2016.08.164 [doi] FAU - Baragetti, A AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy. FAU - Palmen, J AU - Palmen J AD - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK. FAU - Garlaschelli, K AU - Garlaschelli K AD - Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy. FAU - Grigore, L AU - Grigore L AD - Center for the Study of Atherosclerosis - Bassini Hospital, Cinisello Balsamo, Italy; IRCCS - Multimedica Hospital, Sesto San Giovanni, Italy. FAU - Humphries, S E AU - Humphries SE AD - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK. FAU - Talmud, P J AU - Talmud PJ AD - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; IRCCS - Multimedica Hospital, Sesto San Giovanni, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: danilo.norata@unimi.it. LA - eng GR - RG/08/008/25291/British Heart Foundation/United Kingdom PT - Letter DEP - 20160808 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (CLPTM1L protein, human) RN - 0 (Membrane Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (telomerase RNA) RN - 63231-63-0 (RNA) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Asymptomatic Diseases MH - *Cardiovascular Diseases/epidemiology/etiology MH - *Carotid Artery Diseases/complications/diagnosis/genetics MH - Carotid Intima-Media Thickness MH - Disease Progression MH - Humans MH - Incidence MH - Membrane Proteins/*genetics MH - Neoplasm Proteins/*genetics MH - Polymorphism, Single Nucleotide MH - RNA/*genetics MH - Risk Factors MH - Statistics as Topic MH - Telomerase/*genetics MH - Telomere Shortening/*genetics OTO - NOTNLM OT - Cardiovascular OT - Genetics OT - Intima-Media Thickness OT - Telomeres EDAT- 2016/08/18 06:00 MHDA- 2017/10/17 06:00 CRDT- 2016/08/18 06:00 PHST- 2016/07/18 00:00 [received] PHST- 2016/08/07 00:00 [accepted] PHST- 2016/08/18 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] PHST- 2016/08/18 06:00 [entrez] AID - S0167-5273(16)31870-8 [pii] AID - 10.1016/j.ijcard.2016.08.164 [doi] PST - ppublish SO - Int J Cardiol. 2016 Nov 15;223:43-45. doi: 10.1016/j.ijcard.2016.08.164. Epub 2016 Aug 8. PMID- 27750108 OWN - NLM STAT- MEDLINE DCOM- 20171220 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 254 DP - 2016 Nov TI - Drug treatment and adherence of subjects <40 years with diagnosis of heterozygous familial hypercholesterolemia. PG - 172-178 LID - S0021-9150(16)31423-X [pii] LID - 10.1016/j.atherosclerosis.2016.10.020 [doi] AB - BACKGROUND AND AIMS: We aimed at describing the therapeutic approach in young adult patients diagnosed with heterozygous familial hypercholesterolemia (HeFH) and their adherence and persistence to treatment. METHODS: From regional administrative databases, individuals aged /=60 days, and influencing factors using log binomial models. RESULTS: Of 1404 patients, 42.4% were initially treated with a high-efficacy statin. 23.4% of patients showed at least one treatment change. Mean MPR was 68.7% (29.9), and patients showing continued statin use were 47.0%. Therapy modification was significantly associated with a past cardiovascular event (relative risk, RR [95% confidential interval] 2.28 [1.69-3.09]) and at least one lipid test (RR 1.82 [1.31-2.53]). MPR >/=80% was significantly associated with the first statin prescribed (atorvastatin RR 1.28 [1.09-1.51] and rosuvastatin RR 1.21 [1.01-1.44], vs. simvastatin), a past cardiovascular event (RR 1.33 [1.12-1.59]), at least one therapy change (RR 1.28 [1.15-1.43]), at least a lipid test (RR 1.26 [1.07-1.49]). A similar pattern was observed for persistence. CONCLUSIONS: This analysis of young adult HeFH patients showed that therapy change was quite frequent, and probably reflected adjustments according to individual response. Adherence and persistence were inadequate, even in this population at high cardiovascular risk, and they need to be improved through proper patient education and shared treatment decision-making approach. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy. Electronic address: sefap@unimi.it. FAU - Scotti, Lorenza AU - Scotti L AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, via Bicocca degli Arcimboldi 8, 20126 Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Region Lombardia, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, via Bicocca degli Arcimboldi 8, 20126 Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy; IRCCS MultiMedica, via Milanese 300, 20099 Sesto S. Giovanni, MI, Italy. LA - eng PT - Journal Article DEP - 20161012 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - A0JWA85V8F (Atorvastatin) RN - AGG2FN16EV (Simvastatin) SB - IM MH - Adult MH - Atorvastatin/therapeutic use MH - Cardiovascular Diseases/drug therapy/genetics MH - Decision Making MH - Female MH - Follow-Up Studies MH - Heterozygote MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hyperlipoproteinemia Type II/*drug therapy/*genetics MH - Male MH - *Medication Adherence MH - Patient Education as Topic MH - Risk Factors MH - Rosuvastatin Calcium/therapeutic use MH - Simvastatin/therapeutic use MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - *Adherence OT - *Heterozygous familial hypercholesterolemia OT - *Persistence OT - *Statins OT - *Treatment changes EDAT- 2016/10/18 06:00 MHDA- 2017/12/21 06:00 CRDT- 2016/11/06 06:00 PHST- 2016/05/27 00:00 [received] PHST- 2016/10/10 00:00 [revised] PHST- 2016/10/11 00:00 [accepted] PHST- 2016/11/06 06:00 [entrez] PHST- 2016/10/18 06:00 [pubmed] PHST- 2017/12/21 06:00 [medline] AID - S0021-9150(16)31423-X [pii] AID - 10.1016/j.atherosclerosis.2016.10.020 [doi] PST - ppublish SO - Atherosclerosis. 2016 Nov;254:172-178. doi: 10.1016/j.atherosclerosis.2016.10.020. Epub 2016 Oct 12. PMID- 27680308 OWN - NLM STAT- MEDLINE DCOM- 20180807 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 254 DP - 2016 Nov TI - Reply to: "Statins probably do not cause cataracts". PG - 311-312 LID - S0021-9150(16)31372-7 [pii] LID - 10.1016/j.atherosclerosis.2016.09.058 [doi] FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133, Milan, Italy. FAU - Soranna, Davide AU - Soranna D AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy; Istituto Auxologico Italiano, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Regione Lombardia, Piazza Citta di Lombardia 1, 20124, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica, via Milanese 300, 20099, Sesto S. Giovanni (MI), Italy. Electronic address: alberico.catapano@unimi.it. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, 20133, Milan, Italy. LA - eng PT - Letter PT - Comment DEP - 20160920 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM CON - Atherosclerosis. 2016 Nov;254:310. PMID: 27568456 CON - Atherosclerosis. 2016 Aug;251:153-158. PMID: 27323228 MH - *Cataract MH - Humans MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors OTO - NOTNLM OT - *Cataracts OT - *Side effects OT - *Statins EDAT- 2016/09/30 06:00 MHDA- 2018/08/08 06:00 CRDT- 2016/09/30 06:00 PHST- 2016/09/09 00:00 [received] PHST- 2016/09/15 00:00 [accepted] PHST- 2016/09/30 06:00 [pubmed] PHST- 2018/08/08 06:00 [medline] PHST- 2016/09/30 06:00 [entrez] AID - S0021-9150(16)31372-7 [pii] AID - 10.1016/j.atherosclerosis.2016.09.058 [doi] PST - ppublish SO - Atherosclerosis. 2016 Nov;254:311-312. doi: 10.1016/j.atherosclerosis.2016.09.058. Epub 2016 Sep 20. PMID- 27567407 OWN - NLM STAT- MEDLINE DCOM- 20181121 LR - 20181121 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 37 IP - 39 DP - 2016 Oct 14 TI - 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. PG - 2999-3058 LID - 10.1093/eurheartj/ehw272 [doi] FAU - Catapano, Alberico L AU - Catapano AL FAU - Graham, Ian AU - Graham I FAU - De Backer, Guy AU - De Backer G FAU - Wiklund, Olov AU - Wiklund O FAU - Chapman, M John AU - Chapman MJ FAU - Drexel, Heinz AU - Drexel H FAU - Hoes, Arno W AU - Hoes AW FAU - Jennings, Catriona S AU - Jennings CS FAU - Landmesser, Ulf AU - Landmesser U FAU - Pedersen, Terje R AU - Pedersen TR FAU - Reiner, Zeljko AU - Reiner Z FAU - Riccardi, Gabriele AU - Riccardi G FAU - Taskinen, Marja-Riita AU - Taskinen MR FAU - Tokgozoglu, Lale AU - Tokgozoglu L FAU - Verschuren, W M Monique AU - Verschuren WMM FAU - Vlachopoulos, Charalambos AU - Vlachopoulos C FAU - Wood, David A AU - Wood DA FAU - Zamorano, Jose Luis AU - Zamorano JL FAU - Cooney, Marie-Therese AU - Cooney MT CN - ESC Scientific Document Group LA - eng PT - Journal Article PT - Practice Guideline DEP - 20160827 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 SB - IM CIN - Eur Heart J Cardiovasc Pharmacother. 2017 Apr 1;3(2):73-74. PMID: 28363207 MH - Cardiology MH - Cardiovascular Diseases/etiology/*prevention & control MH - Dyslipidemias/complications/*therapy MH - Europe MH - Humans MH - Risk MH - Sex Factors MH - Societies, Medical OTO - NOTNLM OT - *apolipoprotein B OT - *cholesterol OT - *dyslipidaemias OT - *high-density lipoproteins OT - *lipoprotein remnants OT - *low-density lipoproteins OT - *total cardiovascular risk OT - *treatment, adherence OT - *treatment, drugs OT - *treatment, lifestyle OT - *triglycerides IR - Badimon L FIR - Badimon, Lina IR - Funck-Brentano C FIR - Funck-Brentano, Christian IR - Agewall S FIR - Agewall, Stefan IR - Baron-Esquivias G FIR - Baron-Esquivias, Gonzalo IR - Boren J FIR - Boren, Jan IR - Bruckert E FIR - Bruckert, Eric IR - Cordero A FIR - Cordero, Alberto IR - Corsini A FIR - Corsini, Alberto IR - Giannuzzi P FIR - Giannuzzi, Pantaleo IR - Gueyffier F FIR - Gueyffier, Francois IR - Krstacic G FIR - Krstacic, Goran IR - Lettino M FIR - Lettino, Maddalena IR - Lionis C FIR - Lionis, Christos IR - Lip GYH FIR - Lip, Gregory Y H IR - Marques-Vidal P FIR - Marques-Vidal, Pedro IR - Milicic D FIR - Milicic, Davor IR - Pedro-Botet J FIR - Pedro-Botet, Juan IR - Piepoli MF FIR - Piepoli, Massimo F IR - Rigopoulos AG FIR - Rigopoulos, Angelos G IR - Ruschitzka F FIR - Ruschitzka, Frank IR - Tunon J FIR - Tunon, Jose IR - von Eckardstein A FIR - von Eckardstein, Arnold IR - Vrablik M FIR - Vrablik, Michal IR - Weiss TW FIR - Weiss, Thomas W IR - Williams B FIR - Williams, Bryan IR - Windecker S FIR - Windecker, Stephan IR - Zimlichman R FIR - Zimlichman, Reuven IR - Zamorano JL FIR - Zamorano, Jose Luis IR - Aboyans V FIR - Aboyans, Victor IR - Achenbach S FIR - Achenbach, Stephan IR - Agewall S FIR - Agewall, Stefan IR - Badimon L FIR - Badimon, Lina IR - Baron-Esquivias G FIR - Baron-Esquivias, Gonzalo IR - Baumgartner H FIR - Baumgartner, Helmut IR - Bax JJ FIR - Bax, Jeroen J IR - Bueno H FIR - Bueno, Hector IR - Carerj S FIR - Carerj, Scipione IR - Dean V FIR - Dean, Veronica IR - Erol C FIR - Erol, Cetin IR - Fitzsimons D FIR - Fitzsimons, Donna IR - Gaemperli O FIR - Gaemperli, Oliver IR - Kirchhof P FIR - Kirchhof, Paulus IR - Kolh P FIR - Kolh, Philippe IR - Lancellotti P FIR - Lancellotti, Patrizio IR - Lip GYH FIR - Lip, Gregory Y H IR - Nihoyannopoulos P FIR - Nihoyannopoulos, Petros IR - Piepoli MF FIR - Piepoli, Massimo F IR - Ponikowski P FIR - Ponikowski, Piotr IR - Roffi M FIR - Roffi, Marco IR - Torbicki A FIR - Torbicki, Adam IR - Vaz Carneiro A FIR - Vaz Carneiro, Antonio IR - Windecker S FIR - Windecker, Stephan IR - Zelveian PH FIR - Zelveian, Parounak H IR - Siostrzonek P FIR - Siostrzonek, Peter IR - Ibrahimov F FIR - Ibrahimov, Firdovsi IR - Sujayeva V FIR - Sujayeva, Volha IR - Claeys MJ FIR - Claeys, Marc J IR - Pojskic B FIR - Pojskic, Belma IR - Postadzhiyan A FIR - Postadzhiyan, Arman IR - Milicic D FIR - Milicic, Davor IR - Georgiou GC FIR - Georgiou, George C IR - Rosolova H FIR - Rosolova, Hana IR - Klausen C FIR - Klausen, Christian IR - Viigimaa M FIR - Viigimaa, Margus IR - Kervinen K FIR - Kervinen, Kari IR - Kedev S FIR - Kedev, Sasko IR - Ferrieres J FIR - Ferrieres, Jean IR - Petriashvili S FIR - Petriashvili, Shalva IR - Kintscher U FIR - Kintscher, Ulrich IR - Rallidis L FIR - Rallidis, Loukianos IR - Gabor Kiss R FIR - Gabor Kiss, Robert IR - Guethnason T FIR - Guethnason, Thorarinn IR - Maher V FIR - Maher, Vincent IR - Henkin Y FIR - Henkin, Yaakov IR - Mureddu GF FIR - Mureddu, Gian Francesco IR - Mussagaliyeva A FIR - Mussagaliyeva, Aisulu IR - Ibrahimi P FIR - Ibrahimi, Pranvera IR - Mirrakhimov E FIR - Mirrakhimov, Erkin IR - Latkovskis G FIR - Latkovskis, Gustavs IR - Ben Lamin H FIR - Ben Lamin, Hisham IR - Slapikas R FIR - Slapikas, Rimvydas IR - Visser L FIR - Visser, Laurent IR - Dingli P FIR - Dingli, Philip IR - Ivanov V FIR - Ivanov, Victoria IR - Wittekoek J FIR - Wittekoek, Janneke IR - Hovland A FIR - Hovland, Anders IR - Rynkiewicz A FIR - Rynkiewicz, Andrzej IR - Rato Q FIR - Rato, Quiteria IR - Ezhov M FIR - Ezhov, Marat IR - Zavatta M FIR - Zavatta, Marco IR - Nedeljkovic MA FIR - Nedeljkovic, Milan A IR - Pella D FIR - Pella, Daniel IR - Fras Z FIR - Fras, Zlatko IR - Marzal D FIR - Marzal, Domingo IR - Nilsson L FIR - Nilsson, Lennart IR - Mach F FIR - Mach, Francois IR - Addad F FIR - Addad, Faouzi IR - Kayikcioglu M FIR - Kayikcioglu, Meral IR - Mitchenko O FIR - Mitchenko, Olena IR - Wald D FIR - Wald, David EDAT- 2016/08/28 06:00 MHDA- 2018/11/22 06:00 CRDT- 2016/08/28 06:00 PHST- 2016/08/28 06:00 [pubmed] PHST- 2018/11/22 06:00 [medline] PHST- 2016/08/28 06:00 [entrez] AID - ehw272 [pii] AID - 10.1093/eurheartj/ehw272 [doi] PST - ppublish SO - Eur Heart J. 2016 Oct 14;37(39):2999-3058. doi: 10.1093/eurheartj/ehw272. Epub 2016 Aug 27. PMID- 27594540 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 253 DP - 2016 Oct TI - 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). PG - 281-344 LID - S0021-9150(16)31267-9 [pii] LID - 10.1016/j.atherosclerosis.2016.08.018 [doi] CN - Authors/Task Force Members: FAU - Catapano, Alberico L AU - Catapano AL FAU - Graham, Ian AU - Graham I FAU - De Backer, Guy AU - De Backer G FAU - Wiklund, Olov AU - Wiklund O FAU - Chapman, M John AU - Chapman MJ FAU - Drexel, Heinz AU - Drexel H FAU - Hoes, Arno W AU - Hoes AW FAU - Jennings, Catriona S AU - Jennings CS FAU - Landmesser, Ulf AU - Landmesser U FAU - Pedersen, Terje R AU - Pedersen TR FAU - Reiner, Zeljko AU - Reiner Z FAU - Riccardi, Gabriele AU - Riccardi G FAU - Taskinen, Marja-Riita AU - Taskinen MR FAU - Tokgozoglu, Lale AU - Tokgozoglu L FAU - Verschuren, W M Monique AU - Verschuren WM FAU - Vlachopoulos, Charalambos AU - Vlachopoulos C FAU - Wood, David A AU - Wood DA FAU - Zamorano, Jose Luis AU - Zamorano JL LA - eng PT - Journal Article PT - Practice Guideline DEP - 20160901 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 SB - IM CIN - Rev Esp Cardiol (Engl Ed). 2017 Feb;70(2):72-77. PMID: 28131410 MH - Atherosclerosis MH - Cardiology MH - Dyslipidemias/*therapy MH - Humans OTO - NOTNLM OT - *apolipoprotein B OT - *cholesterol OT - *dyslipidaemias OT - *high-density lipoproteins OT - *lipoprotein remnants OT - *low-density lipoproteins OT - *total cardiovascular risk OT - *treatment, adherence OT - *treatment, drugs OT - *treatment, lifestyle OT - *triglycerides EDAT- 2016/09/07 06:00 MHDA- 2018/09/11 06:00 CRDT- 2016/09/06 06:00 PHST- 2016/09/07 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2016/09/06 06:00 [entrez] AID - S0021-9150(16)31267-9 [pii] AID - 10.1016/j.atherosclerosis.2016.08.018 [doi] PST - ppublish SO - Atherosclerosis. 2016 Oct;253:281-344. doi: 10.1016/j.atherosclerosis.2016.08.018. Epub 2016 Sep 1. PMID- 27477186 OWN - NLM STAT- MEDLINE DCOM- 20171221 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 253 DP - 2016 Oct TI - PCSK9 knock-out mice are protected from neointimal formation in response to perivascular carotid collar placement. PG - 214-224 LID - S0021-9150(16)31210-2 [pii] LID - 10.1016/j.atherosclerosis.2016.07.910 [doi] AB - BACKGROUND AND AIMS: Proprotein convertase subtilisin kexin type 9 (PCSK9) induces degradation of the low-density lipoprotein-receptor (LDLR). Smooth muscle cells (SMCs) in human atherosclerotic plaques and cultured SMCs express PCSK9. The present study aimed at defining the role of PCSK9 on vascular response to injury. METHODS: Carotid neointimal lesions were induced by positioning a non-occlusive collar in PCSK9 knock-out (PCSK9(-/-)) and wild type littermate (PCSK9(+/+)) mice. RESULTS: In PCSK9(-/-) mice, we observed a significantly less intimal thickening (p < 0.05), a lower intimal media ratio (p < 0.02), and a tendency to higher lumen area, compared to PCSK9(+/+) mice. When compared with PCSK9(-/-), lesions of PCSK9(+/+) mice had a higher content of SMCs (p < 0.05) and collagen (p < 0.05), while no difference was observed in the accumulation of macrophages. PCSK9 was detectable in both left and right carotids artery in regions occupied by medial and neointimal SMCs. SMCs freshly isolated from PCSK9(-/-), when compared to PCSK9(+/+) cells, showed higher levels of alpha-smooth muscle actin (alpha-SMA; 2.24 +/- 0.36 fold; p < 0.01) and myosin heavy chain II (MHC-II; 8.65 +/- 1.55 fold; p < 0.01), and lower levels of caldesmon mRNA(-54 +/- 14%; p < 0.01). PCSK9(-/-) cells also showed a slower proliferation rate, and an impaired migratory capacity and G1/S progression of the cell cycle. The reconstitution of PCSK9 expression, by retroviral infection of PCSK9(-/-) SMCs, led to a downregulation of alpha-SMA (-56 +/- 2%; p < 0.01), MHC-II (-45% +/- 25.5 fold: p = 0.06) and calponin (-25% +/- 0.8 fold: p < 0.05) and induction of caldesmon mRNA (1.46 +/- 0.3 fold; p < 0.05). Proliferation rate of SMCs PCSK9(-/-) was significantly lower compared to PCSK9 reconstituted cells. CONCLUSIONS: Taken together, the present results suggest that PCSK9, by sustaining SMC synthetic phenotype, proliferation, and migration, may play a pro-atherogenic role in the arterial wall. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Ferri, Nicola AU - Ferri N AD - Dipartimento di Scienze del Farmaco, Universita degli Studi di Padova, Padua, Italy. Electronic address: nicola.ferri@unipd.it. FAU - Marchiano, Silvia AU - Marchiano S AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Tibolla, Gianpaolo AU - Tibolla G AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Baetta, Roberta AU - Baetta R AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Dhyani, Ashish AU - Dhyani A AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Uboldi, Patrizia AU - Uboldi P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy; Multimedica IRCCS, Milan, Italy. FAU - Corsini, Alberto AU - Corsini A AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy; Multimedica IRCCS, Milan, Italy. LA - eng PT - Journal Article DEP - 20160722 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Cholesterol, LDL) RN - 0 (Proto-Oncogene Proteins c-sis) RN - 1B56C968OA (Becaplermin) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Pcsk9 protein, mouse) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM CIN - Atherosclerosis. 2016 Oct;253:275-277. PMID: 27591126 MH - Animals MH - Aorta/metabolism MH - Becaplermin MH - Carotid Arteries/*pathology MH - Carotid Artery Injuries/*pathology MH - Cell Differentiation MH - Cell Movement MH - Cell Proliferation MH - Chemotaxis MH - Cholesterol, LDL/metabolism MH - Cytoskeleton/metabolism MH - Female MH - Heterozygote MH - Humans MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Muscle, Smooth, Vascular/metabolism MH - Myocytes, Smooth Muscle/cytology MH - Neointima/*pathology MH - Phenotype MH - Proprotein Convertase 9/*genetics/*physiology MH - Proto-Oncogene Proteins c-sis/metabolism MH - Tunica Intima/pathology OTO - NOTNLM OT - *Cell migration OT - *Cell proliferation OT - *PCSK9 OT - *Restenosis OT - *Small G proteins OT - *Smooth muscle cells EDAT- 2016/08/02 06:00 MHDA- 2017/12/22 06:00 CRDT- 2016/08/02 06:00 PHST- 2016/03/15 00:00 [received] PHST- 2016/07/15 00:00 [revised] PHST- 2016/07/20 00:00 [accepted] PHST- 2016/08/02 06:00 [pubmed] PHST- 2017/12/22 06:00 [medline] PHST- 2016/08/02 06:00 [entrez] AID - S0021-9150(16)31210-2 [pii] AID - 10.1016/j.atherosclerosis.2016.07.910 [doi] PST - ppublish SO - Atherosclerosis. 2016 Oct;253:214-224. doi: 10.1016/j.atherosclerosis.2016.07.910. Epub 2016 Jul 22. PMID- 27496869 OWN - NLM STAT- MEDLINE DCOM- 20170926 LR - 20181113 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 112 IP - 1 DP - 2016 Oct TI - Biology of proprotein convertase subtilisin kexin 9: beyond low-density lipoprotein cholesterol lowering. PG - 429-42 LID - 10.1093/cvr/cvw194 [doi] AB - Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author 2016. For permissions please email: journals.permissions@oup.com. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy. FAU - Tavori, Hagai AU - Tavori H AD - Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy IRCCS Multimedica, Milan, Italy. FAU - Fazio, Sergio AU - Fazio S AD - Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy IRCCS Multimedica, Milan, Italy alberico.catapano@unimi.it. LA - eng GR - R01 HL132985/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Review PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160805 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Anticholesteremic Agents) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Cholesterol, LDL) RN - 0 (Serine Proteinase Inhibitors) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM MH - Adipose Tissue/drug effects/enzymology MH - Adiposity/drug effects MH - Animals MH - Anticholesteremic Agents/adverse effects/*therapeutic use MH - Biomarkers/blood MH - Blood Glucose/drug effects/metabolism MH - Brain/drug effects/enzymology MH - Cholesterol, LDL/*blood MH - Communicable Diseases/enzymology MH - Down-Regulation MH - Humans MH - Hypercholesterolemia/blood/*drug therapy/enzymology MH - Kidney/drug effects/enzymology MH - Lipid Metabolism/drug effects MH - Liver/drug effects/enzymology MH - Proprotein Convertase 9/*antagonists & inhibitors/metabolism MH - Serine Proteinase Inhibitors/adverse effects/*therapeutic use PMC - PMC5031950 OTO - NOTNLM OT - *APO B OT - *LDL OT - *LDLR OT - *Monoclonal antibodies OT - *PCSK9 EDAT- 2016/08/09 06:00 MHDA- 2017/09/28 06:00 CRDT- 2016/08/07 06:00 PHST- 2016/01/05 00:00 [received] PHST- 2016/07/06 00:00 [accepted] PHST- 2016/08/07 06:00 [entrez] PHST- 2016/08/09 06:00 [pubmed] PHST- 2017/09/28 06:00 [medline] AID - cvw194 [pii] AID - 10.1093/cvr/cvw194 [doi] PST - ppublish SO - Cardiovasc Res. 2016 Oct;112(1):429-42. doi: 10.1093/cvr/cvw194. Epub 2016 Aug 5. PMID- 27246162 OWN - NLM STAT- MEDLINE DCOM- 20180123 LR - 20180418 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 4 IP - 10 DP - 2016 Oct TI - Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. PG - 850-61 LID - 10.1016/S2213-8587(16)30041-9 [doi] LID - S2213-8587(16)30041-9 [pii] AB - Familial hypercholesterolaemia is common in individuals who had a myocardial infarction at a young age. As many as one in 200 people could have heterozygous familial hypercholesterolaemia, and up to one in 300 000 individuals could be homozygous. The phenotypes of heterozygous and homozygous familial hypercholesterolaemia overlap considerably; the response to treatment is also heterogeneous. In this Review, we aim to define a phenotype for severe familial hypercholesterolaemia and identify people at highest risk for cardiovascular disease, based on the concentration of LDL cholesterol in blood and individuals' responsiveness to conventional lipid-lowering treatment. We assess the importance of molecular characterisation and define the role of other cardiovascular risk factors and advanced subclinical coronary atherosclerosis in risk stratification. Individuals with severe familial hypercholesterolaemia might benefit in particular from early and more aggressive cholesterol-lowering treatment (eg, with PCSK9 inhibitors). In addition to better tailored therapy, more precise characterisation of individuals with severe familial hypercholesterolaemia could improve resource use. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Santos, Raul D AU - Santos RD AD - Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, and Preventive Medicine Centre and Cardiology Program, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. Electronic address: rdsf@uol.com.br. FAU - Gidding, Samuel S AU - Gidding SS AD - Nemours Cardiac Center, A I DuPont Hospital for Children, Wilmington, DE, USA. FAU - Hegele, Robert A AU - Hegele RA AD - Department of Medicine and Robarts Research Institute, Schulich School of Medicine, Western University, London, ON, Canada. FAU - Cuchel, Marina A AU - Cuchel MA AD - Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Barter, Philip J AU - Barter PJ AD - School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. FAU - Watts, Gerald F AU - Watts GF AD - Lipid Disorders Clinic, Royal Perth Hospital, The University of Western Australia, Perth, WA, Australia. FAU - Baum, Seth J AU - Baum SJ AD - Preventive Cardiology, Christine E Lynn Women's Health & Wellness Institute, Boca Raton Regional Hospital, Boca Raton, FL, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS Multimedica, Milan, Italy. FAU - Chapman, M John AU - Chapman MJ AD - Pitie-Salpetriere University Hospital, Paris, France. FAU - Defesche, Joep C AU - Defesche JC AD - University of Amsterdam, Academic Medical Center (AMC), Amsterdam, Netherlands. FAU - Folco, Emanuela AU - Folco E AD - International Atherosclerosis Society, Milan, Italy. FAU - Freiberger, Tomas AU - Freiberger T AD - Molecular Genetics Lab, Centre for Cardiovascular Surgery and Transplantation, and Ceitec, Masaryk University, Brno, Czech Republic. FAU - Genest, Jacques AU - Genest J AD - McGill University Health Center, Royal Victoria Hospital, Montreal, QC, Canada. FAU - Hovingh, G Kees AU - Hovingh GK AD - University of Amsterdam, Academic Medical Center (AMC), Amsterdam, Netherlands. FAU - Harada-Shiba, Mariko AU - Harada-Shiba M AD - National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan. FAU - Humphries, Steve E AU - Humphries SE AD - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College of London, London, UK. FAU - Jackson, Ann S AU - Jackson AS AD - International Atherosclerosis Society, Houston, TX, USA. FAU - Mata, Pedro AU - Mata P AD - Fundacion Hipercolesterolemia Familiar, Madrid, Spain. FAU - Moriarty, Patrick M AU - Moriarty PM AD - Atherosclerosis and Lipoprotein-Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA. FAU - Raal, Frederick J AU - Raal FJ AD - Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Al-Rasadi, Khalid AU - Al-Rasadi K AD - Sultan Qaboos University Hospital, Muscat, Oman. FAU - Ray, Kausik K AU - Ray KK AD - School of Public Health, Imperial College London, London, UK. FAU - Reiner, Zelijko AU - Reiner Z AD - European Association for Cardiovascular Prevention and Rehabilitations, Zagreb, Croatia. FAU - Sijbrands, Eric J G AU - Sijbrands EJ AD - Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands. FAU - Yamashita, Shizuya AU - Yamashita S AD - Osaka University Graduate School of Medicine, Suita, Osaka, Japan. CN - International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel LA - eng GR - RG/08/008/25291/British Heart Foundation/United Kingdom PT - Journal Article PT - Review PT - Research Support, Non-U.S. Gov't DEP - 20160527 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Cholesterol, LDL) SB - IM EIN - Lancet Diabetes Endocrinol. 2016 Aug;4(8):e8. PMID: 27373965 MH - Cardiovascular Diseases/*epidemiology/etiology MH - Cholesterol, LDL/blood MH - Female MH - Humans MH - Hyperlipoproteinemia Type II/complications/*epidemiology/*therapy MH - Male MH - Practice Guidelines as Topic MH - Risk Factors MH - Societies, Medical EDAT- 2016/06/02 06:00 MHDA- 2018/01/24 06:00 CRDT- 2016/06/02 06:00 PHST- 2016/02/15 00:00 [received] PHST- 2016/03/24 00:00 [revised] PHST- 2016/04/06 00:00 [accepted] PHST- 2016/06/02 06:00 [entrez] PHST- 2016/06/02 06:00 [pubmed] PHST- 2018/01/24 06:00 [medline] AID - S2213-8587(16)30041-9 [pii] AID - 10.1016/S2213-8587(16)30041-9 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2016 Oct;4(10):850-61. doi: 10.1016/S2213-8587(16)30041-9. Epub 2016 May 27. PMID- 27692125 OWN - NLM STAT- MEDLINE DCOM- 20171026 LR - 20171026 IS - 1885-5857 (Electronic) IS - 1885-5857 (Linking) VI - 69 IP - 10 DP - 2016 Oct TI - 2016 European Guidelines on cardiovascular disease prevention in clinical practice. PG - 939 LID - S1885-5857(16)30270-5 [pii] LID - 10.1016/j.rec.2016.09.009 [doi] FAU - Piepoli, Massimo F AU - Piepoli MF FAU - Hoes, Arno W AU - Hoes AW FAU - Agewall, Stefan AU - Agewall S FAU - Albus, Christian AU - Albus C FAU - Brotons, Carlos AU - Brotons C FAU - Catapano, Alberico L AU - Catapano AL FAU - Cooney, Marie-Therese AU - Cooney MT FAU - Corra, Ugo AU - Corra U FAU - Cosyns, Bernard AU - Cosyns B FAU - Deaton, Christi AU - Deaton C FAU - Graham, Ian AU - Graham I FAU - Hall, Michael Stephen AU - Hall MS FAU - Richard Hobbs, F D AU - Richard Hobbs FD FAU - Lochen, Maja-Lisa AU - Lochen ML FAU - Lollgen, Herbert AU - Lollgen H FAU - Marques-Vidal, Pedro AU - Marques-Vidal P FAU - Perk, Joep AU - Perk J FAU - Prescott, Eva AU - Prescott E FAU - Redon, Josep AU - Redon J FAU - Richter, Dimitrios J AU - Richter DJ FAU - Sattar, Naveed AU - Sattar N FAU - Smulders, Yvo AU - Smulders Y FAU - Tiberi, Monica AU - Tiberi M FAU - Bart van der Worp, H AU - Bart van der Worp H FAU - van Dis, Ineke AU - van Dis I FAU - Monique Verschuren, W M AU - Monique Verschuren WM LA - eng LA - spa PT - Journal Article PL - Spain TA - Rev Esp Cardiol (Engl Ed) JT - Revista espanola de cardiologia (English ed.) JID - 101587954 SB - IM CIN - Rev Esp Cardiol (Engl Ed). 2016 Oct;69(10 ):894-899. PMID: 27692123 MH - Cardiovascular Diseases/*prevention & control MH - *Ethnic Groups MH - Europe MH - Humans MH - Practice Guidelines as Topic MH - Risk Factors EDAT- 2016/10/04 06:00 MHDA- 2017/10/27 06:00 CRDT- 2016/10/04 06:00 PHST- 2016/06/22 00:00 [received] PHST- 2016/09/08 00:00 [accepted] PHST- 2016/10/04 06:00 [entrez] PHST- 2016/10/04 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] AID - S1885-5857(16)30270-5 [pii] AID - 10.1016/j.rec.2016.09.009 [doi] PST - ppublish SO - Rev Esp Cardiol (Engl Ed). 2016 Oct;69(10):939. doi: 10.1016/j.rec.2016.09.009. PMID- 27664503 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 252 DP - 2016 Sep TI - 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). PG - 207-274 LID - S0021-9150(16)30214-3 [pii] LID - 10.1016/j.atherosclerosis.2016.05.037 [doi] CN - Authors/Task Force Members: FAU - Piepoli, Massimo F AU - Piepoli MF FAU - Hoes, Arno W AU - Hoes AW FAU - Agewall, Stefan AU - Agewall S AD - Societie: European Society of Cardiology (ESC). FAU - Albus, Christian AU - Albus C AD - International Society of Behavioural Medicine (ISBM). FAU - Brotons, Carlos AU - Brotons C AD - WONCA Europe. FAU - Catapano, Alberico L AU - Catapano AL AD - Societie: European Atherosclerosis Society (EAS). FAU - Cooney, Marie-Therese AU - Cooney MT AD - Societie: European Society of Cardiology (ESC). FAU - Corra, Ugo AU - Corra U AD - Societie: European Society of Cardiology (ESC). FAU - Cosyns, Bernard AU - Cosyns B AD - Societie: European Society of Cardiology (ESC). FAU - Deaton, Christi AU - Deaton C AD - Societie: European Society of Cardiology (ESC). FAU - Graham, Ian AU - Graham I AD - Societie: European Society of Cardiology (ESC). FAU - Hall, Michael Stephen AU - Hall MS AD - International Diabetes Federation European Region (IDF Europe). FAU - Hobbs, F D Richard AU - Hobbs FDR AD - WONCA Europe. FAU - Lochen, Maja-Lisa AU - Lochen ML AD - Societie: European Society of Cardiology (ESC). FAU - Lollgen, Herbert AU - Lollgen H AD - International Federation of Sport Medicine (FIMS). FAU - Marques-Vidal, Pedro AU - Marques-Vidal P AD - Societie: European Society of Cardiology (ESC). FAU - Perk, Joep AU - Perk J AD - Societie: European Society of Cardiology (ESC). FAU - Prescott, Eva AU - Prescott E AD - Societie: European Society of Cardiology (ESC). FAU - Redon, Josep AU - Redon J AD - Societie: European Society of Hypertension (ESH). FAU - Richter, Dimitrios J AU - Richter DJ AD - Societie: European Society of Cardiology (ESC). FAU - Sattar, Naveed AU - Sattar N AD - Societie: European Association for the Study of Diabetes (EASD). FAU - Smulders, Yvo AU - Smulders Y AD - Societie: European Society of Cardiology (ESC). FAU - Tiberi, Monica AU - Tiberi M AD - Societie: European Society of Cardiology (ESC). FAU - Bart van der Worp, H AU - Bart van der Worp H AD - Societie: European Stroke Organisation (ESO). FAU - van Dis, Ineke AU - van Dis I AD - Societie: European Heart Network (EHN). FAU - Verschuren, W M Monique AU - Verschuren WMM AD - Societie: European Society of Cardiology (ESC). LA - eng PT - Journal Article PT - Practice Guideline PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 SB - IM MH - Cardiology MH - Cardiovascular Diseases/*prevention & control MH - Europe MH - Societies, Medical OTO - NOTNLM OT - *Blood pressure OT - *Clinical settings OT - *Diabetes OT - *Guidelines OT - *Healthy lifestyle OT - *Lipid OT - *Nutrition OT - *Physical activity OT - *Population OT - *Prevention OT - *Primary care OT - *Psychosocial factors OT - *Rehabilitation OT - *Risk assessment OT - *Risk management OT - *Smoking OT - *Stakeholder EDAT- 2016/09/25 06:00 MHDA- 2018/09/11 06:00 CRDT- 2016/09/25 06:00 PHST- 2016/09/25 06:00 [entrez] PHST- 2016/09/25 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] AID - S0021-9150(16)30214-3 [pii] AID - 10.1016/j.atherosclerosis.2016.05.037 [doi] PST - ppublish SO - Atherosclerosis. 2016 Sep;252:207-274. doi: 10.1016/j.atherosclerosis.2016.05.037. PMID- 27494444 OWN - NLM STAT- MEDLINE DCOM- 20171221 LR - 20180517 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 252 DP - 2016 Sep TI - Prevalence of potential familial hypercholesteremia (FH) in 54,811 statin-treated patients in clinical practice. PG - 1-8 LID - S0021-9150(16)30306-9 [pii] LID - 10.1016/j.atherosclerosis.2016.07.007 [doi] AB - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a life-threatening disease, characterized by elevated LDL-C levels and a premature, increased risk of coronary heart disease (CHD) that is globally underdiagnosed. The percentage of patients with possible or probable FH in various countries was examined in the Dyslipidemia International Study (DYSIS). METHODS: DYSIS is a multinational, cross-sectional observational study of 54,811 adult outpatients treated with statin therapy. The percentages of patients with high levels of LDL-C, and with possible or probable FH, were assessed using the Dutch scoring method for FH across 29 countries, in age subgroups for the analysis population and among diabetes patients. RESULTS: Despite statin therapy, 16.1% (range 4.4-27.6%) of patients had LDL-C >3.6 mmol/L (140 mg/dL) across countries and the prevalence of possible FH was 15.0% (range 5.5-27.8%) and 1.1% (range 0.0-5.4%) for probable FH. The highest percentages of probable FH occurred in Egypt (5.4%), the Baltic states (4.2%), Russia (3.2%), and Slovenia (3.1%), with the lowest rates in Israel (0.0%), Canada (0.2%), and Sweden (0.3%). Rates of FH were the highest in younger patients (45-54 years) for secondary prevention, regardless of the presence/absence of diabetes. CONCLUSIONS: Despite statin therapy, high LDL-C levels and rates of possible and probable FH were observed in some countries. The prevalence of FH was the highest in younger age patients, and >60% of patients with probable FH displayed CHD. Earlier diagnosis and treatment of patients with FH are needed to reduce CHD risk in these patients. CI - Copyright (c) 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Lautsch, Dominik AU - Lautsch D AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Hacettepe University Hospital, Ankara, Turkey. FAU - Ferrieres, Jean AU - Ferrieres J AD - Department of Cardiology, Toulouse University School of Medicine, Toulouse Cedex, France. FAU - Horack, Martin AU - Horack M AD - Institut Herzinfarktforschung, Ludwigshafen, Germany. FAU - Farnier, Michel AU - Farnier M AD - Lipid Clinic, Point Medical, Dijon, France. FAU - Toth, Peter P AU - Toth PP AD - CGH Medical Center, Sterling, IL, USA; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Brudi, Philippe AU - Brudi P AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Tomassini, Joanne E AU - Tomassini JE AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Ambegaonkar, Baishali AU - Ambegaonkar B AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Gitt, Anselm K AU - Gitt AK AD - Klinikum der Stadt Ludwigshafen, Med. Klinik B and Stiftung Institut Herzinfarktforschung, Ludwigshafen, Germany. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20160714 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Age Factors MH - Aged MH - Anticholesteremic Agents/therapeutic use MH - Cardiovascular Diseases/complications/epidemiology MH - Cholesterol, LDL/blood MH - Coronary Artery Disease/complications MH - Cross-Sectional Studies MH - Dyslipidemias/drug therapy MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hyperlipoproteinemia Type II/diagnosis/drug therapy/*epidemiology MH - International Cooperation MH - Male MH - Middle Aged MH - Outpatients MH - Prevalence MH - Secondary Prevention OTO - NOTNLM OT - *CHD OT - *Combination therapy OT - *Familial hypercholesterolemia OT - *LDL-C OT - *Statin EDAT- 2016/08/06 06:00 MHDA- 2017/12/22 06:00 CRDT- 2016/08/06 06:00 PHST- 2015/12/21 00:00 [received] PHST- 2016/06/20 00:00 [revised] PHST- 2016/07/07 00:00 [accepted] PHST- 2016/08/06 06:00 [entrez] PHST- 2016/08/06 06:00 [pubmed] PHST- 2017/12/22 06:00 [medline] AID - S0021-9150(16)30306-9 [pii] AID - 10.1016/j.atherosclerosis.2016.07.007 [doi] PST - ppublish SO - Atherosclerosis. 2016 Sep;252:1-8. doi: 10.1016/j.atherosclerosis.2016.07.007. Epub 2016 Jul 14. PMID- 27323228 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20180516 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 251 DP - 2016 Aug TI - Statin use and risk of cataract: A nested case-control study within a healthcare database. PG - 153-158 LID - S0021-9150(16)30265-9 [pii] LID - 10.1016/j.atherosclerosis.2016.06.020 [doi] AB - BACKGROUND AND AIMS: We aimed to assess the association between exposure to statins and hospitalization for cataract. METHODS: A population-based, nested case-control study was performed on a cohort of 134,441 patients from Lombardy (Italy), newly treated with statins between 2005 and 2007. Cases were patients hospitalized for cataract or lens extraction surgery after initial statin prescription until December 31, 2012. For each case patient, up to 5 controls were randomly selected from the cohort and matched by gender, age at cohort entry, and date of index prescription. Logistic regression was used to model the outcome risk associated with low (proportion of days covered, PDC 25-49%), intermediate (PDC 50-74%), and high (PDC >/= 75%) adherence compared with very-low adherence (PDC < 25%). RESULTS: 1334 case patients were matched to 6601 controls. Mean age (SD) of cases and controls was about 70 years (9 years) and 51% of them were men. There was a slight but continuous trend toward an increased risk of cataract as adherence to statin therapy increased in the adjusted risk models, with a significant odds ratio of 1.19 (95% CI 1.01-1.40%) for PDC 50-74% and 1.20 (95% CI 1.02-1.40) for PDC >/= 75% vs. PDC < 25%, respectively. There was no statistical evidence that the effect of statins on cataract risk differed according to statin potency at starting therapy. CONCLUSIONS: Statin therapy was associated with a modestly increased risk of cataract surgery. Nevertheless, in view of the overwhelming benefit of statins for reduction of CV events, clinical practice for statins therapy does not need to change. CI - Copyright (c) 2016. Published by Elsevier Ireland Ltd. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Soranna, Davide AU - Soranna D AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca Degli Arcimboldi 8, 20126, Milan, Italy; Istituto Auxologico Italiano, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca Degli Arcimboldi 8, 20126, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Regione Lombardia, Piazza Citta di Lombardia 1, 20124, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy; IRCCS MultiMedica, Via Milanese 300, 20099, Sesto S. Giovanni, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. LA - eng PT - Journal Article DEP - 20160611 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM CIN - Atherosclerosis. 2016 Nov;254:310. PMID: 27568456 CIN - Atherosclerosis. 2016 Nov;254:311-312. PMID: 27680308 MH - Aged MH - Case-Control Studies MH - Cataract/chemically induced/*prevention & control MH - Cohort Studies MH - Electronic Health Records MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Hypercholesterolemia/complications/drug therapy MH - Italy MH - Logistic Models MH - Male MH - Medication Adherence MH - Middle Aged MH - Odds Ratio MH - Patient Compliance MH - Risk Factors OTO - NOTNLM OT - *Cataract OT - *Databases OT - *Drug safety OT - *Nested case-control study OT - *Statins EDAT- 2016/06/21 06:00 MHDA- 2017/12/27 06:00 CRDT- 2016/06/21 06:00 PHST- 2016/02/10 00:00 [received] PHST- 2016/06/07 00:00 [revised] PHST- 2016/06/09 00:00 [accepted] PHST- 2016/06/21 06:00 [entrez] PHST- 2016/06/21 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] AID - S0021-9150(16)30265-9 [pii] AID - 10.1016/j.atherosclerosis.2016.06.020 [doi] PST - ppublish SO - Atherosclerosis. 2016 Aug;251:153-158. doi: 10.1016/j.atherosclerosis.2016.06.020. Epub 2016 Jun 11. PMID- 27222591 OWN - NLM STAT- MEDLINE DCOM- 20180409 LR - 20190112 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 37 IP - 29 DP - 2016 Aug 1 TI - 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). PG - 2315-2381 LID - 10.1093/eurheartj/ehw106 [doi] FAU - Piepoli, Massimo F AU - Piepoli MF FAU - Hoes, Arno W AU - Hoes AW FAU - Agewall, Stefan AU - Agewall S AD - Societie: European Society of Cardiology (ESC). FAU - Albus, Christian AU - Albus C AD - International Society of Behavioural Medicine (ISBM). FAU - Brotons, Carlos AU - Brotons C AD - WONCA Europe. FAU - Catapano, Alberico L AU - Catapano AL AD - Societie: European Atherosclerosis Society (EAS). FAU - Cooney, Marie-Therese AU - Cooney MT AD - Societie: European Society of Cardiology (ESC). FAU - Corra, Ugo AU - Corra U AD - Societie: European Society of Cardiology (ESC). FAU - Cosyns, Bernard AU - Cosyns B AD - Societie: European Society of Cardiology (ESC). FAU - Deaton, Christi AU - Deaton C AD - Societie: European Society of Cardiology (ESC). FAU - Graham, Ian AU - Graham I AD - Societie: European Society of Cardiology (ESC). FAU - Hall, Michael Stephen AU - Hall MS AD - International Diabetes Federation European Region (IDF Europe). FAU - Hobbs, F D Richard AU - Hobbs FDR AD - WONCA Europe. FAU - Lochen, Maja-Lisa AU - Lochen ML AD - Societie: European Society of Cardiology (ESC). FAU - Lollgen, Herbert AU - Lollgen H AD - International Federation of Sport Medicine (FIMS). FAU - Marques-Vidal, Pedro AU - Marques-Vidal P AD - Societie: European Society of Cardiology (ESC). FAU - Perk, Joep AU - Perk J AD - Societie: European Society of Cardiology (ESC). FAU - Prescott, Eva AU - Prescott E AD - Societie: European Society of Cardiology (ESC). FAU - Redon, Josep AU - Redon J AD - Societie: European Society of Hypertension (ESH). FAU - Richter, Dimitrios J AU - Richter DJ AD - Societie: European Society of Cardiology (ESC). FAU - Sattar, Naveed AU - Sattar N AD - Societie: European Association for the Study of Diabetes (EASD). FAU - Smulders, Yvo AU - Smulders Y AD - Societie: European Society of Cardiology (ESC). FAU - Tiberi, Monica AU - Tiberi M AD - Societie: European Society of Cardiology (ESC). FAU - van der Worp, H Bart AU - van der Worp HB AD - Societie: European Stroke Organisation (ESO). FAU - van Dis, Ineke AU - van Dis I AD - Societie: European Heart Network (EHN). FAU - Verschuren, W M Monique AU - Verschuren WMM AD - Societie: European Society of Cardiology (ESC). FAU - Binno, Simone AU - Binno S CN - ESC Scientific Document Group LA - eng PT - Journal Article PT - Practice Guideline DEP - 20160523 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Antihypertensive Agents) RN - 0 (Biomarkers) SB - IM MH - Adult MH - Age Factors MH - Aged MH - Antihypertensive Agents/therapeutic use MH - Biomarkers/metabolism MH - Cardiac Rehabilitation/economics/*methods MH - Cardiovascular Diseases/economics/ethnology/*prevention & control MH - Cost-Benefit Analysis MH - Diabetic Angiopathies/prevention & control MH - Diagnostic Imaging/methods MH - Exercise/physiology MH - General Practice/methods MH - Health Promotion/methods MH - Healthy Diet MH - Healthy Lifestyle MH - Humans MH - Hyperlipidemias/prevention & control MH - Hypertension MH - Middle Aged MH - Multiple Chronic Conditions MH - Pedigree MH - Practice Patterns, Physicians'/standards MH - Risk Assessment MH - Sex Factors MH - Smoking Cessation MH - Socioeconomic Factors PMC - PMC4986030 OTO - NOTNLM OT - *Blood pressure OT - *Clinical settings OT - *Diabetes OT - *Guidelines OT - *Healthy lifestyle OT - *Lipid OT - *Nutrition OT - *Physical activity OT - *Population OT - *Prevention OT - *Primary care OT - *Psychosocial factors OT - *Rehabilitation OT - *Risk assessment OT - *Risk management OT - *Smoking OT - *Stakeholder IR - De Backer G FIR - De Backer, Guy IR - Roffi M FIR - Roffi, Marco IR - Aboyans V FIR - Aboyans, Victor IR - Bachl N FIR - Bachl, Norbert IR - Bueno H FIR - Bueno, Hector IR - Carerj S FIR - Carerj, Scipione IR - Cho L FIR - Cho, Leslie IR - Cox J FIR - Cox, John IR - De Sutter J FIR - De Sutter, Johan IR - Egidi G FIR - Egidi, Gunther IR - Fisher M FIR - Fisher, Miles IR - Fitzsimons D FIR - Fitzsimons, Donna IR - Franco OH FIR - Franco, Oscar H IR - Guenoun M FIR - Guenoun, Maxime IR - Jennings C FIR - Jennings, Catriona IR - Jug B FIR - Jug, Borut IR - Kirchhof P FIR - Kirchhof, Paulus IR - Kotseva K FIR - Kotseva, Kornelia IR - Lip GY FIR - Lip, Gregory Yh IR - Mach F FIR - Mach, Francois IR - Mancia G FIR - Mancia, Giuseppe IR - Bermudo FM FIR - Bermudo, Franz Martin IR - Mezzani A FIR - Mezzani, Alessandro IR - Niessner A FIR - Niessner, Alexander IR - Ponikowski P FIR - Ponikowski, Piotr IR - Rauch B FIR - Rauch, Bernhard IR - Ryden L FIR - Ryden, Lars IR - Stauder A FIR - Stauder, Adrienne IR - Turc G FIR - Turc, Guillaume IR - Wiklund O FIR - Wiklund, Olov IR - Windecker S FIR - Windecker, Stephan IR - Zamorano JL FIR - Zamorano, Jose Luis IR - Zamorano JL FIR - Zamorano, Jose Luis IR - Aboyans V FIR - Aboyans, Victor IR - Achenbach S FIR - Achenbach, Stephan IR - Agewall S FIR - Agewall, Stefan IR - Badimon L FIR - Badimon, Lina IR - Baron-Esquivias G FIR - Baron-Esquivias, Gonzalo IR - Baumgartner H FIR - Baumgartner, Helmut IR - Bax JJ FIR - Bax, Jeroen J IR - Bueno H FIR - Bueno, Hector IR - Carerj S FIR - Carerj, Scipione IR - Dean V FIR - Dean, Veronica IR - Erol C FIR - Erol, Cetin IR - Fitzsimons D FIR - Fitzsimons, Donna IR - Gaemperli O FIR - Gaemperli, Oliver IR - Kirchhof P FIR - Kirchhof, Paulus IR - Kolh P FIR - Kolh, Philippe IR - Lancellotti P FIR - Lancellotti, Patrizio IR - Lip GY FIR - Lip, Gregory Yh IR - Nihoyannopoulos P FIR - Nihoyannopoulos, Petros IR - Piepoli MF FIR - Piepoli, Massimo F IR - Ponikowski P FIR - Ponikowski, Piotr IR - Roffi M FIR - Roffi, Marco IR - Torbicki A FIR - Torbicki, Adam IR - Vaz Carneiro A FIR - Vaz Carneiro, Antonio IR - Windecker S FIR - Windecker, Stephan IR - Metzler B FIR - Metzler, Bernhard IR - Najafov R FIR - Najafov, Ruslan IR - Stelmashok V FIR - Stelmashok, Valeriy IR - De Maeyer C FIR - De Maeyer, Catherine IR - Dilic M FIR - Dilic, Mirza IR - Gruev I FIR - Gruev, Ivan IR - Milicic D FIR - Milicic, Davor IR - Vaverkova H FIR - Vaverkova, Helena IR - Gustafsson I FIR - Gustafsson, Ida IR - Attia I FIR - Attia, Ihab IR - Duishvili D FIR - Duishvili, Davit IR - Kostova N FIR - Kostova, Nela IR - Ferrieres J FIR - Ferrieres, Jean IR - Klimiashvili Z FIR - Klimiashvili, Zurab IR - Hambrecht R FIR - Hambrecht, Rainer IR - Tsioufis K FIR - Tsioufis, Konstantinos IR - Szabados E FIR - Szabados, Eszter IR - Andersen K FIR - Andersen, Karl IR - Vaughan C FIR - Vaughan, Carl IR - Zafrir B FIR - Zafrir, Barak IR - Novo S FIR - Novo, Salvatore IR - Davletov K FIR - Davletov, Kairat IR - Jashari F FIR - Jashari, Fisnik IR - Kerimkulova A FIR - Kerimkulova, Alina IR - Mintale I FIR - Mintale, Iveta IR - Saade G FIR - Saade, Georges IR - Petrulioniene Z FIR - Petrulioniene, Zaneta IR - Delagardelle C FIR - Delagardelle, Charles IR - Magri CJ FIR - Magri, Caroline J IR - Rudi V FIR - Rudi, Victor IR - Oukerraj L FIR - Oukerraj, Latifa IR - Colkesen BE FIR - Colkesen, B Ersen IR - Schirmer H FIR - Schirmer, Henrik IR - Jankowski P FIR - Jankowski, Piotr IR - Dos Reis RP FIR - Dos Reis, Roberto Palma IR - Gherasim D FIR - Gherasim, Daniel IR - Nedogoda S FIR - Nedogoda, Sergey IR - Zavatta M FIR - Zavatta, Marco IR - Giga V FIR - Giga, Vojislav IR - Filipova S FIR - Filipova, Slavomira IR - Padial LR FIR - Padial, Luis Rodriguez IR - Kiessling A FIR - Kiessling, Anna IR - Mach F FIR - Mach, Francois IR - Mahdhaoui A FIR - Mahdhaoui, Abdallah IR - Ural D FIR - Ural, Dilek IR - Nesukay E FIR - Nesukay, Elena IR - Gale C FIR - Gale, Chris EDAT- 2016/05/26 06:00 MHDA- 2018/04/10 06:00 CRDT- 2016/05/26 06:00 PHST- 2016/05/26 06:00 [entrez] PHST- 2016/05/26 06:00 [pubmed] PHST- 2018/04/10 06:00 [medline] AID - ehw106 [pii] AID - 10.1093/eurheartj/ehw106 [doi] PST - ppublish SO - Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. PMID- 27444125 OWN - NLM STAT- MEDLINE DCOM- 20180412 LR - 20181202 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Jul 22 TI - Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. PG - 30060 LID - 10.1038/srep30060 [doi] AB - Since the evidence regarding statin therapy in PAH has not been conclusive, we assessed the impact of statin therapy in PAH through a systematic review and meta-analysis of available studies. We searched selected databases up to August 1, 2015 to identify the studies investigating the effect of statin administration on PAH. Meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Meta-analysis of 8 studies with 665 patients did not suggest any significant improvement in 6-min walking distance (6MWD) by statin therapy (weighed mean difference [WMD]: -6.08 m, 95% confidence interval [CI]: -25.66, 13.50, p = 0.543; Q = 8.41, I(2) = 28.64%). Likewise, none of the other indices including pulmonary arterial pressure (WMD: -0.97 mmHg, 95%CI: -4.39, 2.44, p = 0.577; Q = 14.64, I(2) = 79.51%), right atrial pressure (WMD: 1.01 mmHg, 95%CI: -0.93, 2.96, p = 0.307; Q = 44.88, I(2) = 95.54%), cardiac index (WMD: 0.05 L/min/m(2), 95%CI: -0.05, 0.15, p = 0.323; Q = 3.82, I(2) = 21.42%), and pulmonary vascular resistance (WMD: -1.42 dyn*s/cm(5), 95%CI: -72.11, 69.27, p = 0.969; Q = 0.69, I(2) = 0%) was significantly altered by statin therapy. In conclusion, the results of the meta-analysis did not show a statistically significant effect of statin therapy in the improvement of 6MWD, pulmonary arterial pressure, right atrial pressure, cardiac index and pulmonary vascular resistance. FAU - Rysz-Gorzynska, Magdalena AU - Rysz-Gorzynska M AD - Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. AD - Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland. FAU - Gluba-Brzozka, Anna AU - Gluba-Brzozka A AD - Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland. AD - Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. AD - Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. FAU - Serban, Maria-Corina AU - Serban MC AD - Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. AD - Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. FAU - Mikhailidis, Dimitri P AU - Mikhailidis DP AD - Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK. FAU - Ursoniu, Sorin AU - Ursoniu S AD - Department of Functional Sciences, Discipline of Public Health, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. FAU - Toth, Peter P AU - Toth PP AD - Preventive Cardiology, CGH Medical Center, Sterling, Illinois, USA. AD - The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. FAU - Bittner, Vera AU - Bittner V AD - Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Watts, Gerald F AU - Watts GF AD - Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. FAU - Lip, Gregory Y H AU - Lip GY AD - University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, UK. FAU - Rysz, Jacek AU - Rysz J AD - Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland. AD - Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences University of Milan and IRCCS Multimedica Milano Italy. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. AD - Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20160722 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Arterial Pressure MH - Atrial Pressure MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypertension, Pulmonary/*drug therapy MH - Male MH - Treatment Outcome MH - Vascular Resistance PMC - PMC4957081 EDAT- 2016/07/23 06:00 MHDA- 2018/04/13 06:00 CRDT- 2016/07/23 06:00 PHST- 2016/04/20 00:00 [received] PHST- 2016/06/27 00:00 [accepted] PHST- 2016/07/23 06:00 [entrez] PHST- 2016/07/23 06:00 [pubmed] PHST- 2018/04/13 06:00 [medline] AID - srep30060 [pii] AID - 10.1038/srep30060 [doi] PST - epublish SO - Sci Rep. 2016 Jul 22;6:30060. doi: 10.1038/srep30060. PMID- 27353126 OWN - NLM STAT- MEDLINE DCOM- 20180220 LR - 20181202 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 23 IP - 11 DP - 2016 Jul TI - 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). PG - NP1-NP96 LID - 10.1177/2047487316653709 [doi] CN - Authors/Task Force Members FAU - Piepoli, Massimo F AU - Piepoli MF FAU - Hoes, Arno W AU - Hoes AW FAU - Agewall, Stefan AU - Agewall S AD - Societies: European Society of Cardiology (ESC). FAU - Albus, Christian AU - Albus C AD - International Society of Behavioural Medicine (ISBM). FAU - Brotons, Carlos AU - Brotons C AD - WONCA Europe. FAU - Catapano, Alberico L AU - Catapano AL AD - European Atherosclerosis Society (EAS). FAU - Cooney, Marie-Therese AU - Cooney MT AD - Societies: European Society of Cardiology (ESC). FAU - Corra, Ugo AU - Corra U AD - Societies: European Society of Cardiology (ESC). FAU - Cosyns, Bernard AU - Cosyns B AD - Societies: European Society of Cardiology (ESC). FAU - Deaton, Christi AU - Deaton C AD - Societies: European Society of Cardiology (ESC). FAU - Graham, Ian AU - Graham I AD - Societies: European Society of Cardiology (ESC). FAU - Hall, Michael Stephen AU - Hall MS AD - International Diabetes Federation European Region (IDF Europe). FAU - Hobbs, F D Richard AU - Hobbs FD AD - WONCA Europe. FAU - Lochen, Maja-Lisa AU - Lochen ML AD - Societies: European Society of Cardiology (ESC). FAU - Lollgen, Herbert AU - Lollgen H AD - International Federation of Sport Medicine (FIMS). FAU - Marques-Vidal, Pedro AU - Marques-Vidal P AD - Societies: European Society of Cardiology (ESC). FAU - Perk, Joep AU - Perk J AD - Societies: European Society of Cardiology (ESC). FAU - Prescott, Eva AU - Prescott E AD - Societies: European Society of Cardiology (ESC). FAU - Redon, Josep AU - Redon J AD - European Society of Hypertension (ESH). FAU - Richter, Dimitrios J AU - Richter DJ AD - Societies: European Society of Cardiology (ESC). FAU - Sattar, Naveed AU - Sattar N AD - European Association for the Study of Diabetes (EASD). FAU - Smulders, Yvo AU - Smulders Y AD - Societies: European Society of Cardiology (ESC). FAU - Tiberi, Monica AU - Tiberi M AD - Societies: European Society of Cardiology (ESC). FAU - van der Worp, H Bart AU - van der Worp HB AD - European Stroke Organisation (ESO). FAU - van Dis, Ineke AU - van Dis I AD - European Heart Network (EHN). FAU - Verschuren, W M Monique AU - Verschuren WM AD - Societies: European Society of Cardiology (ESC). CN - Additional Contributor: Simone Binno (Italy) CN - Document Reviewers: FAU - De Backer, Guy AU - De Backer G FAU - Roffi, Marco AU - Roffi M FAU - Aboyans, Victor AU - Aboyans V AD - Societies: European Society of Cardiology (ESC). FAU - Bachl, Norbert AU - Bachl N AD - International Federation of Sport Medicine (FIMS). FAU - Bueno, Hector AU - Bueno H AD - Societies: European Society of Cardiology (ESC). FAU - Carerj, Scipione AU - Carerj S AD - Societies: European Society of Cardiology (ESC). FAU - Cho, Leslie AU - Cho L AD - Societies: European Society of Cardiology (ESC). FAU - Cox, John AU - Cox J AD - WONCA Europe. FAU - De Sutter, Johan AU - De Sutter J AD - Societies: European Society of Cardiology (ESC). FAU - Egidi, Gunther AU - Egidi G AD - Societies: European Society of Cardiology (ESC). FAU - Fisher, Miles AU - Fisher M AD - European Association for the Study of Diabetes (EASD). FAU - Fitzsimons, Donna AU - Fitzsimons D AD - Societies: European Society of Cardiology (ESC). FAU - Franco, Oscar H AU - Franco OH AD - Societies: European Society of Cardiology (ESC). FAU - Guenoun, Maxime AU - Guenoun M AD - Societies: European Society of Cardiology (ESC). FAU - Jennings, Catriona AU - Jennings C AD - Societies: European Society of Cardiology (ESC). FAU - Jug, Borut AU - Jug B AD - European Heart Network (EHN). FAU - Kirchhof, Paulus AU - Kirchhof P AD - Societies: European Society of Cardiology (ESC). FAU - Kotseva, Kornelia AU - Kotseva K AD - Societies: European Society of Cardiology (ESC). FAU - Lip, Gregory Y H AU - Lip GY AD - Societies: European Society of Cardiology (ESC). FAU - Mach, Francois AU - Mach F AD - Societies: European Society of Cardiology (ESC). FAU - Mancia, Giuseppe AU - Mancia G AD - European Society of Hypertension (ESH). FAU - Bermudo, Franz Martin AU - Bermudo FM AD - International Diabetes Federation European Region (IDF Europe). FAU - Mezzani, Alessandro AU - Mezzani A AD - Societies: European Society of Cardiology (ESC). FAU - Niessner, Alexander AU - Niessner A AD - Societies: European Society of Cardiology (ESC). FAU - Ponikowski, Piotr AU - Ponikowski P AD - Societies: European Society of Cardiology (ESC). FAU - Rauch, Bernhard AU - Rauch B AD - Societies: European Society of Cardiology (ESC). FAU - Ryden, Lars AU - Ryden L AD - Societies: European Society of Cardiology (ESC). FAU - Stauder, Adrienne AU - Stauder A AD - International Society of Behavioural Medicine (ISBM). FAU - Turc, Guillaume AU - Turc G AD - European Stroke Organisation (ESO). FAU - Wiklund, Olov AU - Wiklund O AD - European Atherosclerosis Society (EAS). FAU - Windecker, Stephan AU - Windecker S AD - Societies: European Society of Cardiology (ESC). FAU - Zamorano, Jose Luis AU - Zamorano JL AD - Societies: European Society of Cardiology (ESC). LA - eng PT - Journal Article PT - Practice Guideline DEP - 20160627 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 SB - IM MH - Advisory Committees MH - *Cardiac Rehabilitation MH - Cardiology MH - *Cardiovascular Diseases/prevention & control/therapy MH - Europe MH - Humans MH - Risk Factors MH - Societies, Medical OTO - NOTNLM OT - *Blood pressure OT - *Clinical settings OT - *Diabetes OT - *Guidelines OT - *Healthy lifestyle OT - *Lipid OT - *Nutrition OT - *Physical activity OT - *Population OT - *Prevention OT - *Primary care OT - *Psychosocial factors OT - *Rehabilitation OT - *Risk assessment OT - *Risk management OT - *Smoking OT - *Stakeholder EDAT- 2016/06/30 06:00 MHDA- 2018/02/21 06:00 CRDT- 2016/06/30 06:00 PHST- 2016/06/30 06:00 [entrez] PHST- 2016/06/30 06:00 [pubmed] PHST- 2018/02/21 06:00 [medline] AID - 2047487316653709 [pii] AID - 10.1177/2047487316653709 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2016 Jul;23(11):NP1-NP96. doi: 10.1177/2047487316653709. Epub 2016 Jun 27. PMID- 26948872 OWN - NLM STAT- MEDLINE DCOM- 20170213 LR - 20170213 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 21 DP - 2016 Jun TI - Impact of substitution among generic drugs on persistence and adherence: A retrospective claims data study from 2 Local Healthcare Units in the Lombardy Region of Italy. PG - 1-8 LID - 10.1016/j.atherosclerosissup.2016.02.001 [doi] LID - S1567-5688(16)30023-X [pii] AB - BACKGROUND: The use of generics, equivalent but less expensive drugs, is an important opportunity to reduce healthcare expenditure. METHODS: The purpose of this study was to investigate the effect of substitution between unbranded generics on persistence and adherence to therapy in two Italian Local Health Units (ASL) in real-world clinical practice in 5 therapeutic areas using tracing drugs. Substitution of generic drugs is any change in the name of the manufacturer of the generic drug. The therapeutic areas were: diabetes (metformin); hypertension (amlodipine); dyslipidemia (simvastatin); psychiatry (sertraline); cardiology (propafenone); osteoporosis (alendronate). The retrospective analysis was carried out on the administrative databases of two Local Healthcare Units (ASL - Azienda sanitaria locale Bergamo (BG) and Pavia (PV)) in the Lombardy Region of Italy. The correlation between persistence and adherence with the different cohorts of generic substitution frequency within each therapeutic area was then calculated. RESULTS: According to the inclusion criteria, 23,773 patients were evaluated. Patients were observed for a period of 36 months starting from the first drug delivery (index date). The median age of the overall population was above 61 years in all therapeutic areas. The generic drug substitution occurred in 61.5% of patients (BG: 57.6% and PV: 65.4% respectively); Hypertension was the therapeutic area with the highest percentage of patients with substitutions. Patients' adherence, evaluated by the Medical Possession Rate (MPR) and persistence to the treatment decreases with the increase in the frequency of generic substitutions. This observation was confirmed by a statistically significant negative correlation (p-value of <0.001) between the adherence and persistence and the number of generic substitutions in each therapeutic area and Local Healthcare Units (ASL). DISCUSSION: Adherence is one of the pillars of the patient's health management in the control and prevention of progression of the disease. Several factors, such as ageing, comorbidities, and polypharmacy, may affect adherence and influence the outcome of treatments. These results are in line with studies supporting the possibility that the change of package appearance each time a new prescription is dispensed may create confusion and ultimately reduce patients' adherence. Clinicians and decision makers should consider the impact of frequent generic substitutions on persistence and adherence, which may influence efficacy and/or safety. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Colombo, Giorgio L AU - Colombo GL AD - Department of Drug Sciences, University of Pavia, Italy. FAU - Agabiti-Rosei, Enrico AU - Agabiti-Rosei E AD - Division of Medicine and Surgery, Spedali Civili, Brescia, Italy. FAU - Margonato, Alberto AU - Margonato A AD - Division of Cardiology, San Raffaele University Hospital, Milan, Italy. FAU - Mencacci, Claudio AU - Mencacci C AD - Department of Neuroscience, A.O. Fatebenefratelli e Oftalmico, Milan, Italy. FAU - Montecucco, Carlo Maurizio AU - Montecucco CM AD - Division of Rheumatology, IRCCS Policlinico S Matteo, University of Pavia, Italy. FAU - Trevisan, Roberto AU - Trevisan R AD - Unit of Diabetology, Ospedali Riuniti di Bergamo, Bergamo, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, and IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20160213 PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Drugs, Generic) SB - IM MH - *Administrative Claims, Healthcare MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Comorbidity MH - Databases, Factual MH - Drug Prescriptions MH - *Drug Substitution MH - Drugs, Generic/*therapeutic use MH - Female MH - Health Knowledge, Attitudes, Practice MH - Humans MH - *Insurance Claim Review MH - Italy MH - Male MH - *Medication Adherence MH - Middle Aged MH - Polypharmacy MH - Retrospective Studies MH - Time Factors OTO - NOTNLM OT - Adherence OT - Administrative databases OT - Compliance OT - Drugs EDAT- 2016/03/08 06:00 MHDA- 2017/02/14 06:00 CRDT- 2016/03/08 06:00 PHST- 2016/03/08 06:00 [entrez] PHST- 2016/03/08 06:00 [pubmed] PHST- 2017/02/14 06:00 [medline] AID - S1567-5688(16)30023-X [pii] AID - 10.1016/j.atherosclerosissup.2016.02.001 [doi] PST - ppublish SO - Atheroscler Suppl. 2016 Jun;21:1-8. doi: 10.1016/j.atherosclerosissup.2016.02.001. Epub 2016 Feb 13. PMID- 26976330 OWN - NLM STAT- In-Process LR - 20181113 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1862 IP - 6 DP - 2016 Jun TI - Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation. PG - 1182-90 LID - 10.1016/j.bbadis.2016.03.007 [doi] LID - S0925-4439(16)30053-9 [pii] AB - AIM: The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis. METHODS AND RESULTS: PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (-80.36+/-11.5% and -95.53+/-4.46%), while in WT mice transplanted with bone marrow from either WT or PTX3 KO mice, the reduction was less dramatic (-45.55+/-1.37% and -53.39+/-9.8%), thus pointing to a protective effect independent of a hematopoietic cell's derived PTX3. By using P-selectin/PTX3 double KO mice, we further excluded a role for P-selectin, a target of PTX3 released by neutrophils, in vascular protection played by PTX3. In agreement with a minor role for hematopoietic cell-derived PTX3, platelet activation (assessed by flow cytometric expression of markers of platelet activation) was similar in PTX3 KO and WT mice as were haemostatic properties. Histological analysis indicated that PTX3 localizes within the thrombus and the vessel wall, and specific experiments with the N-terminal and the C-terminal PTX3 domain showed the ability of PTX3 to selectively dampen either fibrinogen or collagen induced platelet adhesion and aggregation. CONCLUSION: PTX3 interacts with fibrinogen and collagen and, by dampening their pro-thrombotic effects, plays a protective role during arterial thrombosis. CI - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Bonacina, F AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Barbieri, S S AU - Barbieri SS AD - IRCCS, Centro Cardiologico Monzino, Milan, Italy. FAU - Cutuli, L AU - Cutuli L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Amadio, P AU - Amadio P AD - IRCCS, Centro Cardiologico Monzino, Milan, Italy. FAU - Doni, A AU - Doni A AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Sironi, M AU - Sironi M AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Tartari, S AU - Tartari S AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Mantovani, A AU - Mantovani A AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Bottazzi, B AU - Bottazzi B AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Garlanda, C AU - Garlanda C AD - IRCCS, Humanitas Research Foundation, Bruzzano, Milan, Italy. FAU - Tremoli, E AU - Tremoli E AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS, Centro Cardiologico Monzino, Milan, Italy. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Milan, Italy; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: danilo.norata@unimi.it. LA - eng GR - 669415/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160311 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 SB - IM PMC - PMC4856734 OTO - NOTNLM OT - *Arterial thrombosis OT - *Collagen and fibrinogen OT - *P-selectin OT - *PTX3 OT - *Vessel wall EDAT- 2016/03/16 06:00 MHDA- 2016/03/16 06:00 CRDT- 2016/03/16 06:00 PHST- 2015/11/26 00:00 [received] PHST- 2016/02/17 00:00 [revised] PHST- 2016/03/10 00:00 [accepted] PHST- 2016/03/16 06:00 [entrez] PHST- 2016/03/16 06:00 [pubmed] PHST- 2016/03/16 06:00 [medline] AID - S0925-4439(16)30053-9 [pii] AID - 10.1016/j.bbadis.2016.03.007 [doi] PST - ppublish SO - Biochim Biophys Acta. 2016 Jun;1862(6):1182-90. doi: 10.1016/j.bbadis.2016.03.007. Epub 2016 Mar 11. PMID- 28533705 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20181113 IS - 1520-765X (Print) IS - 1520-765X (Linking) VI - 18 IP - Suppl C DP - 2016 Apr 12 TI - Current practice in identifying and treating cardiovascular risk, with a focus on residual risk associated with atherogenic dyslipidaemia. PG - C2-C12 LID - 10.1093/eurheartj/suw009 [doi] AB - A panel of European experts on lipids and cardiovascular disease discussed clinical approaches to managing cardiovascular risk in clinical practice, including residual cardiovascular risk associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence, and its impact on cardiovascular risk. Atherogenic dyslipidaemia can be defined by high fasting triglyceride levels (>/=2.3 mmol/L) and low high-density lipoprotein cholesterol (HDL-c) levels (/=5.6 mmol/L), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favourable benefit-risk profile. Cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy, and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk. FAU - Ferrari, Roberto AU - Ferrari R AD - Department of Cardiology and LTTA Centre, University Hospital of Ferrara and Maria Cecilia Hospital, GVM Care & Research, E.S: Health Science Foundation, Cotignola, Italy. FAU - Aguiar, Carlos AU - Aguiar C AD - Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental, EPE, Carnaxide, Portugal. FAU - Alegria, Eduardo AU - Alegria E AD - Cardiology Department, Policlinica Gipuzkoa, San Sebastian, Spain. FAU - Bonadonna, Riccardo C AU - Bonadonna RC AD - Division of Endocrinology, Department of Clinical and Experimental Medicine, University of Parma and Azienda Ospedaliera Universitaria of Parma, Parma, Italy. FAU - Cosentino, Francesco AU - Cosentino F AD - Cardiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Elisaf, Moses AU - Elisaf M AD - Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece. FAU - Farnier, Michel AU - Farnier M AD - Lipid Clinic, Point Medical, Dijon, France. FAU - Ferrieres, Jean AU - Ferrieres J AD - Cardiovascular Preventive Department, Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France. FAU - Filardi, Pasquale Perrone AU - Filardi PP AD - Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. FAU - Hancu, Nicolae AU - Hancu N AD - Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. FAU - Kayikcioglu, Meral AU - Kayikcioglu M AD - Department of Cardiology, Ege University Medical School, Izmir, Turkey. FAU - Mello E Silva, Alberto AU - Mello E Silva A AD - Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental, EPE, Lisbon, Portugal. AD - Nova Medical School, Faculdade de Ciencias Medicas, Lisbon, Portugal. FAU - Millan, Jesus AU - Millan J AD - Internal Medicine Service, Hospital General Universitario Gregorio Maranon, Facultad de Medicina de la Universidad Complutense, Madrid, Spain. FAU - Reiner, Zeljko AU - Reiner Z AD - Department of Internal Medicine, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Hacettepe University, Ankara, Turkey. FAU - Valensi, Paul AU - Valensi P AD - Department of Endocrinology Diabetology Nutrition, Jean Verdier Hospital, APHP, Paris Nord University, CRNH-IdF, CINFO, Bondy, France. FAU - Viigimaa, Margus AU - Viigimaa M AD - Institute of Cardiovascular Medicine, North Estonia Medical Centre, Tallinn University of Technology, Tallinn, Estonia. FAU - Vrablik, Michal AU - Vrablik M AD - Third Department of Internal Medicine, First Medical Faculty, Charles University, Prague, Czech Republic. FAU - Zambon, Alberto AU - Zambon A AD - Clinica Medica, Department of Medicine, University of Padova, Padova, Italy. FAU - Zamorano, Jose Luis AU - Zamorano JL AD - Head of Cardiology, University Alcala de Henares, Hospital Ramon y Cajal, Madrid, Spain. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy. LA - eng PT - Journal Article PL - England TA - Eur Heart J Suppl JT - European heart journal supplements : journal of the European Society of Cardiology JID - 100886647 OTO - NOTNLM OT - Atherogenic dyslipidaemia OT - Cardiovascular risk OT - Fenofibrate OT - Fenofibrate-statin combination therapy OT - Residual cardiovascular risk OT - Statin EDAT- 2017/05/24 06:00 MHDA- 2017/05/24 06:01 CRDT- 2017/05/24 06:00 PHST- 2017/05/24 06:00 [entrez] PHST- 2017/05/24 06:00 [pubmed] PHST- 2017/05/24 06:01 [medline] AID - 10.1093/eurheartj/suw009 [doi] AID - suw009 [pii] PST - ppublish SO - Eur Heart J Suppl. 2016 Apr 12;18(Suppl C):C2-C12. doi: 10.1093/eurheartj/suw009. PMID- 28533704 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20180705 IS - 1520-765X (Print) IS - 1520-765X (Linking) VI - 18 IP - Suppl C DP - 2016 Apr 12 TI - Residual cardiovascular risk. PG - C1 LID - 10.1093/eurheartj/suw010 [doi] FAU - Ferrari, Roberto AU - Ferrari R AD - Department of Cardiology and LTTA Centre, University Hospital of Ferrara and Maria Cecilia Hospital, GVM Care & Research, E.S: Health Science Foundation, Cotignola, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy. LA - eng PT - Editorial PL - England TA - Eur Heart J Suppl JT - European heart journal supplements : journal of the European Society of Cardiology JID - 100886647 EDAT- 2017/05/24 06:00 MHDA- 2017/05/24 06:01 CRDT- 2017/05/24 06:00 PHST- 2017/05/24 06:00 [entrez] PHST- 2017/05/24 06:00 [pubmed] PHST- 2017/05/24 06:01 [medline] AID - 10.1093/eurheartj/suw010 [doi] AID - suw010 [pii] PST - ppublish SO - Eur Heart J Suppl. 2016 Apr 12;18(Suppl C):C1. doi: 10.1093/eurheartj/suw010. PMID- 26811267 OWN - NLM STAT- MEDLINE DCOM- 20170130 LR - 20170727 IS - 1578-1879 (Electronic) IS - 0214-9168 (Linking) VI - 28 IP - 2 DP - 2016 Mar-Apr TI - [Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy]. PG - 87-93 LID - 10.1016/j.arteri.2015.12.001 [doi] LID - S0214-9168(15)00171-0 [pii] AB - LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. CI - Copyright (c) 2015. Published by Elsevier Espana. CN - Panel Europeo de Expertos. Version Espanola del Grupo de trabajo sobre Dislipemia Aterogenica LA - spa PT - Journal Article TT - Consenso sobre tratamiento farmacologico de la dislipidemia aterogenica con terapia combinada estatina-fenofibrato. DEP - 20160119 PL - Spain TA - Clin Investig Arterioscler JT - Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis JID - 9208512 RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Triglycerides) RN - U202363UOS (Fenofibrate) SB - IM MH - Atherosclerosis/*drug therapy/pathology MH - Cardiovascular Diseases/blood/prevention & control MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Consensus MH - Drug Therapy, Combination MH - Dyslipidemias/*drug therapy/pathology MH - Fenofibrate/administration & dosage/*therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*therapeutic use MH - Hypolipidemic Agents/administration & dosage/therapeutic use MH - Triglycerides/blood OTO - NOTNLM OT - *Asociacion estatina-fenofibrato OT - *Atherogenic dyslipidemia OT - *Dislipidemia aterogenica OT - *Lipid lowering combination therapy OT - *Statine-fenofibrate association OT - *Terapia combinada hipolipemiante IR - Aguiar C FIR - Aguiar, Carlos IR - Alegria E FIR - Alegria, Eduardo IR - Bonnadonna RC FIR - Bonnadonna, Ricardo C IR - Catapano AL FIR - Catapano, Alberico L IR - Consentido F FIR - Consentido, Francesco IR - Elisaf M FIR - Elisaf, Moses IR - Farnier M FIR - Farnier, Michel IR - Fierrieres J FIR - Fierrieres, Jean IR - Filardi PP FIR - Filardi, Pasquale Perronre IR - Hancu N FIR - Hancu, Nicolae IR - Kayikcioglu M FIR - Kayikcioglu, Meral IR - Mello e Silva A FIR - Mello e Silva, Alberto IR - Millan J FIR - Millan, Jesus IR - Reiner Z FIR - Reiner, Zeljko IR - Tokgozoglu L FIR - Tokgozoglu, Lale IR - Valensi P FIR - Valensi, Paul IR - Viigimaa M FIR - Viigimaa, Margas IR - Vrablik M FIR - Vrablik, Michal IR - Zambon A FIR - Zambon, Alberto IR - Zamorano JL FIR - Zamorano, Jose Luis IR - Ferrari R FIR - Ferrari, Roberto IR - Millan J FIR - Millan, Jesus IR - Blasco M FIR - Blasco, Mariano IR - Brea A FIR - Brea, Angel IR - Diaz A FIR - Diaz, Angel IR - Santos PG FIR - Santos, Pedro Gonzales IR - Hernandez Mijares A FIR - Hernandez Mijares, Antonio IR - Mantilla T FIR - Mantilla, Teresa IR - Pedro-Botet J FIR - Pedro-Botet, Juan IR - Pinto X FIR - Pinto, Xavier EDAT- 2016/01/27 06:00 MHDA- 2017/01/31 06:00 CRDT- 2016/01/27 06:00 PHST- 2015/12/23 00:00 [received] PHST- 2016/01/27 06:00 [entrez] PHST- 2016/01/27 06:00 [pubmed] PHST- 2017/01/31 06:00 [medline] AID - S0214-9168(15)00171-0 [pii] AID - 10.1016/j.arteri.2015.12.001 [doi] PST - ppublish SO - Clin Investig Arterioscler. 2016 Mar-Apr;28(2):87-93. doi: 10.1016/j.arteri.2015.12.001. Epub 2016 Jan 19. PMID- 26717273 OWN - NLM STAT- MEDLINE DCOM- 20161025 LR - 20161230 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 245 DP - 2016 Feb TI - Identification and management of patients with statin-associated symptoms in clinical practice: A clinician survey. PG - 111-7 LID - 10.1016/j.atherosclerosis.2015.12.015 [doi] LID - S0021-9150(15)30242-2 [pii] AB - BACKGROUND AND AIMS: Discontinuation of statin therapy by patients with hypercholesterolemia because of the onset of side-effects (statin-associated symptoms [SAS]) increases the risk of cardiovascular morbidity and mortality. We aimed to understand how patients with SAS, particularly those with statin-associated muscle symptoms (SAMS), are identified and managed in the outpatient setting. METHODS: A web-based survey involving 60 clinicians in each of 12 countries and 90 clinicians in the US was conducted. Clinicians answered questions about the diagnostic criteria, estimated incidence of SAS, and choice of treatment for patients with SAS. RESULTS: Overall, 810 clinicians (78% cardiologists) completed the survey. An average of 72% of patients with potential SAS were reported to present with muscle-related symptoms (range across countries [RAC] 50-87%) that could be SAMS. Clinicians took a range of steps to confirm SAMS in these patients, including discontinuation of statin (average 59%; RAC 48-67%); re-challenge with >/= 2 statins (average 74%; RAC 60-85%); modification of statin regimen (average 76%; RAC 65-85%); or a combination of these steps. Overall, 6% of patients with hypercholesterolemia were estimated to eventually have SAS (RAC 2-12%). In patients with SAS, on average 52% continued to receive a low-dose statin, usually with other lipid-lowering therapies (LLT). Of the remaining 49%, 38% received alternative LLT only; 11% did not receive any LLT. CONCLUSION: There is some consistency and stringency in clinical practice for identifying patients with SAS; however, a structured work-up for identification, followed by a defined therapeutic algorithm, may improve their management. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Hovingh, G Kees AU - Hovingh GK AD - Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. Electronic address: g.k.hovingh@amc.uva.nl. FAU - Gandra, Shravanthi R AU - Gandra SR AD - Amgen Inc., One Amgen Center Dr., MS 28-3-A, Thousand Oaks, CA 91320, USA. FAU - McKendrick, Jan AU - McKendrick J AD - PRMA Consulting Ltd, Cygnus House, 1 Waterfront Business Park, Fleet, Hampshire GU51 3QT, UK. FAU - Dent, Ricardo AU - Dent R AD - Amgen Inc., One Amgen Center Dr., MS 28-3-A, Thousand Oaks, CA 91320, USA. FAU - Wieffer, Heather AU - Wieffer H AD - PRMA Consulting Ltd, Cygnus House, 1 Waterfront Business Park, Fleet, Hampshire GU51 3QT, UK. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Via Balzaretti 9, Milan 20133, Italy. FAU - Oh, Paul AU - Oh P AD - Toronto Rehabilitation Institute, 347 Rumsey Road, Toronto, Ontario M4G 1R7, Canada. FAU - Rosenson, Robert S AU - Rosenson RS AD - Mount Sinai Heart, Mount Sinai Icahn School of Medicine, 1425 Madison Ave, MC1 Level, New York 10029, USA. FAU - Stroes, Erik S AU - Stroes ES AD - Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20151211 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Aged MH - Cardiovascular Diseases/*drug therapy/epidemiology MH - Cross-Sectional Studies MH - Female MH - Global Health MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Male MH - Middle Aged MH - Morbidity/trends MH - *Surveys and Questionnaires MH - Survival Rate/trends OTO - NOTNLM OT - Hypercholesterolemia OT - Statin OT - Statin intolerance OT - Statin-associated symptoms EDAT- 2015/12/31 06:00 MHDA- 2016/10/26 06:00 CRDT- 2015/12/31 06:00 PHST- 2015/07/12 00:00 [received] PHST- 2015/12/03 00:00 [revised] PHST- 2015/12/07 00:00 [accepted] PHST- 2015/12/31 06:00 [entrez] PHST- 2015/12/31 06:00 [pubmed] PHST- 2016/10/26 06:00 [medline] AID - S0021-9150(15)30242-2 [pii] AID - 10.1016/j.atherosclerosis.2015.12.015 [doi] PST - ppublish SO - Atherosclerosis. 2016 Feb;245:111-7. doi: 10.1016/j.atherosclerosis.2015.12.015. Epub 2015 Dec 11. PMID- 26563188 OWN - NLM STAT- MEDLINE DCOM- 20161013 LR - 20181113 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 72 IP - 2 DP - 2016 Feb TI - A simple informative intervention in primary care increases statin adherence. PG - 227-34 LID - 10.1007/s00228-015-1975-z [doi] AB - PURPOSE: To assess the effectiveness of an informative intervention on general practitioners aimed at improving patients' adherence to statin therapy. METHODS: In the local health unit (LHU) of Bergamo, Lombardy (Italy), each general practitioner received a synthetic scientific document on dyslipidaemia and statins and aggregated data on adherence in 2006 for his/her patients compared to the means in the LHU and in his/her working district. Furthermore, a sample of seven districts received also a table of adherence levels for single patients. Patient's level data were retrieved from the health care utilisation databases of the LHU. Adherence parameters (proportion of patients with only one prescription, medication possession ratio [MPR] and proportion of non-persistent patients) were assessed after 1 year of follow-up. RESULTS: Overall, 5833 and 4788 new statin users were enrolled before and after the intervention, respectively. The percentage of patients with only one prescription decreased from 28.0 to 23.9 % (p < 0.001). MPR increased from 70.3 to 76.0 % (p < 0.001), and proportion of patients with MPR >/= 80 % increased from 45.4 to 56.4 % (p < 0.001). The persistence also showed an improvement, both in terms of decreasing proportion of non-persistent (from 51.9 to 41.4 %, p < 0.001) and of increasing duration of continued therapy (from 235 to 264 mean days of persistent therapy, p < 0.001). There were not significant differences between the two types of intervention. CONCLUSIONS: This intervention resulted in an overall improvement of the short-term adherence to therapy. This tool can be replicated in other local contexts and with other chronic therapies. FAU - Casula, Manuela AU - Casula M AUID- ORCID: http://orcid.org/0000-0002-5124-5361 AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. sefap@unimi.it. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. FAU - Piccinelli, Rossana AU - Piccinelli R AD - Local Pharmaceutical Service, LHU of Bergamo, via Gallicciolli 4, 24121, Bergamo, Italy. FAU - Zambon, Antonella AU - Zambon A AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - De Fendi, Luisa AU - De Fendi L AD - Local Pharmaceutical Service, LHU of Bergamo, via Gallicciolli 4, 24121, Bergamo, Italy. FAU - Scotti, Lorenza AU - Scotti L AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Via Bicocca degli Arcimboldi 8, 20126, Milan, Italy. FAU - Gambera, Marco AU - Gambera M AD - Local Pharmaceutical Service, LHU of Bergamo, via Gallicciolli 4, 24121, Bergamo, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. AD - IRCCS MultiMedica, via Milanese 300, 20099 Sesto S. Giovanni, Milan, Italy. FAU - Filippi, Alessandro AU - Filippi A AD - Italian Society of General Medicine (SIMG), Via del Pignoncino 9-11, 50142, Florence, Italy. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151112 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Dyslipidemias/*drug therapy MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Male MH - Medication Adherence/*statistics & numerical data MH - Middle Aged MH - *Patient Education as Topic MH - Primary Health Care OTO - NOTNLM OT - Adherence OT - General practice OT - Informative intervention OT - Persistence OT - Statin therapy EDAT- 2015/11/14 06:00 MHDA- 2016/10/14 06:00 CRDT- 2015/11/14 06:00 PHST- 2015/06/22 00:00 [received] PHST- 2015/10/30 00:00 [accepted] PHST- 2015/11/14 06:00 [entrez] PHST- 2015/11/14 06:00 [pubmed] PHST- 2016/10/14 06:00 [medline] AID - 10.1007/s00228-015-1975-z [doi] AID - 10.1007/s00228-015-1975-z [pii] PST - ppublish SO - Eur J Clin Pharmacol. 2016 Feb;72(2):227-34. doi: 10.1007/s00228-015-1975-z. Epub 2015 Nov 12. PMID- 26777475 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20171116 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 26 IP - 2 DP - 2016 Feb TI - Subclinical atherosclerosis is associated with Epicardial Fat Thickness and hepatic steatosis in the general population. PG - 141-53 LID - 10.1016/j.numecd.2015.10.013 [doi] LID - S0939-4753(15)30205-2 [pii] AB - BACKGROUND AND AIMS: Abdominal obesity and hepatic steatosis are ectopic fat depots associated with Metabolic Syndrome (MetS). Epicardial Fat Thickness (EFT) is a newly discovered one, increasing with obesity, insulin resistance and MetS. Therefore we studied whether different ectopic fat markers, and EFT in particular, are associated with MetS and markers of subclinical cardiovascular disease. METHODS AND RESULTS: 868 subjects from the PLIC Study were included, EFT, aortic calcifications, carotid Intima-Media Thickness (c-IMT) and echocardiographic parameters were determined by ultrasound; extra-cardiac atherosclerotic lesions were defined in presence of plaques at both carotid and aortic levels. Hepatic steatosis degrees were defined according to a scoring system. Abdominal adiposity was determined using Dual X-ray Absorbimetry (DEXA). Independently from age, women showed higher EFT versus men (4.5 (0.20-9.00) mm vs 4.00 (0.10-8.00) mm, p = 0.013); EFT was thicker in post-menopausal women (independently from hormone-replacement therapy). EFT, liver steatosis and abdominal adiposity increased with MetS (p < 0.001). EFT was the only ectopic fat marker associated with cardiac dysfunction (OR = 1.340 [1.088-1.651 95% C.I., p = 0.006); liver steatosis and EFT were associated with extra-cardiac plaques (OR = 2.529 [1.328-4.819] 95% C.I., p < 0.001 and OR = 1.195 [1.008-1.299] 95% C.I., p = 0.042; respectively). On top of cardiovascular risk factors, only EFT improved the discrimination of subjects with cardiac dysfunction and atherosclerotic plaques. CONCLUSIONS: EFT is associated with left ventricular dysfunction and subclinical atherosclerosis. Our data suggest that EFT may represent an additional tool for the stratification of cardiovascular risk. CI - Copyright (c) 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Baragetti, A AU - Baragetti A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Pisano, G AU - Pisano G AD - Dipartimento di Medicina Interna, Centro Studi Malattie Metaboliche del Fegato - Ca Granda IRCCS Fondazione Ospedale Policlinico, Milan, Italy. FAU - Bertelli, C AU - Bertelli C AD - Dipartimento di Medicina Interna, Centro Studi Malattie Metaboliche del Fegato - Ca Granda IRCCS Fondazione Ospedale Policlinico, Milan, Italy. FAU - Garlaschelli, K AU - Garlaschelli K AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Grigore, L AU - Grigore L AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Fracanzani, A L AU - Fracanzani AL AD - Dipartimento di Medicina Interna, Centro Studi Malattie Metaboliche del Fegato - Ca Granda IRCCS Fondazione Ospedale Policlinico, Milan, Italy. FAU - Fargion, S AU - Fargion S AD - Dipartimento di Medicina Interna, Centro Studi Malattie Metaboliche del Fegato - Ca Granda IRCCS Fondazione Ospedale Policlinico, Milan, Italy. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; William Harvey Research Institute, Barts and The London School of Medicine & Dentistry Queen's Mary University, London, United Kingdom. Electronic address: danilo.norata@unimi.it. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; Multimedica Hospital - IRCCS, Sesto San Giovanni, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151102 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 SB - IM MH - Absorptiometry, Photon MH - Adipose Tissue MH - *Adiposity MH - Aged MH - Aortic Diseases/*complications/diagnostic imaging MH - Asymptomatic Diseases MH - Atherosclerosis/diagnostic imaging/*etiology MH - Carotid Artery Diseases/diagnostic imaging/*etiology MH - Carotid Intima-Media Thickness MH - Chi-Square Distribution MH - Echocardiography, Doppler, Color MH - Fatty Liver/*complications/diagnostic imaging MH - Female MH - Humans MH - Linear Models MH - Logistic Models MH - Male MH - Metabolic Syndrome/*complications/diagnosis MH - Middle Aged MH - Multivariate Analysis MH - Obesity/*complications/diagnosis MH - Odds Ratio MH - Pericardium MH - Plaque, Atherosclerotic MH - Predictive Value of Tests MH - Risk Factors MH - Sex Factors MH - Vascular Calcification/diagnostic imaging/*etiology MH - Ventricular Dysfunction, Left/diagnostic imaging/etiology OTO - NOTNLM OT - Cardiovascular OT - Epicardial fat OT - Steatosis EDAT- 2016/01/19 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/01/19 06:00 PHST- 2015/09/11 00:00 [received] PHST- 2015/10/26 00:00 [accepted] PHST- 2016/01/19 06:00 [entrez] PHST- 2016/01/19 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - S0939-4753(15)30205-2 [pii] AID - 10.1016/j.numecd.2015.10.013 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2016 Feb;26(2):141-53. doi: 10.1016/j.numecd.2015.10.013. Epub 2015 Nov 2. PMID- 26923679 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20180605 IS - 1875-533X (Electronic) IS - 0929-8673 (Linking) VI - 23 IP - 10 DP - 2016 TI - Niemann-Pick C1-Like 1 (NPC1L1) Inhibition and Cardiovascular Diseases. PG - 983-99 AB - Circulating levels of cholesterol are derived from either endogenous production or intestinal absorption of dietary and biliary cholesterol. Niemann-Pick C1-Like 1 (NPC1L1) is a transmembrane protein that plays a key role in the intestinal absorption of cholesterol by facilitating its uptake through vesicular endocytosis. NPC1L1 is the molecular target of ezetimibe which binds its extracellular loop and inhibits sterol absorption without affecting the absorption of other molecules. Ezetimibe significantly reduces plasma levels of total and low density lipoprotein cholesterol (LDL-C) as monotherapy or when added to statins, the association with a low dose of statin is of particular interest for patients experiencing statin-related side effects. The recent results of the IMPROVE-IT study, which evaluated the cardiovascular effect of ezetimibe added to simvastatin therapy in subjects who had had an acute coronary syndrome and with LDL-C levels within the recommended range, showed that a further LDL-C lowering reduced the incidence of cardiovascular events. To date, ezetimibe represents the only inhibitor of NPC1L1 available for clinical use, however, novel aminoss- lactam ezetimibe derivatives have been synthesized and their efficacy to inhibit NPC1L1 protein and decrease plasma cholesterol levels is under evaluation. FAU - Pirillo, A AU - Pirillo A FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences - Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy. Alberico.Catapano@unimi.it. FAU - Norata, G D AU - Norata GD LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Med Chem JT - Current medicinal chemistry JID - 9440157 RN - 0 (Membrane Proteins) RN - 0 (NPC1L1 protein, human) RN - AGG2FN16EV (Simvastatin) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Cardiovascular Diseases/*drug therapy/metabolism MH - Ezetimibe/chemical synthesis/chemistry/*pharmacology MH - Humans MH - Membrane Proteins/*antagonists & inhibitors MH - Simvastatin/chemistry/*pharmacology EDAT- 2016/03/01 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/03/01 06:00 PHST- 2015/10/20 00:00 [received] PHST- 2016/01/27 00:00 [revised] PHST- 2016/02/27 00:00 [accepted] PHST- 2016/03/01 06:00 [entrez] PHST- 2016/03/01 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - CMC-EPUB-74031 [pii] PST - ppublish SO - Curr Med Chem. 2016;23(10):983-99. PMID- 25416041 OWN - NLM STAT- MEDLINE DCOM- 20161103 LR - 20181113 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 23 IP - 2 DP - 2016 Jan TI - Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. PG - 194-205 LID - 10.1177/2047487314560664 [doi] AB - BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. METHODS: Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. RESULTS: Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). CONCLUSION: Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis. CI - (c) The European Society of Cardiology 2014. FAU - Willeit, Peter AU - Willeit P AD - The Department of Public Health and Primary Care, University of Cambridge, UK Department of Neurology, Medical University Innsbruck, Austria. FAU - Thompson, Simon G AU - Thompson SG AD - The Department of Public Health and Primary Care, University of Cambridge, UK. FAU - Agewall, Stefan AU - Agewall S AD - Institute of Clinical Sciences, University of Oslo, and the Department of Cardiology, Oslo University Hospital Ulleval, Norway. FAU - Bergstrom, Goran AU - Bergstrom G AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden. FAU - Bickel, Horst AU - Bickel H AD - Department of Psychiatry and Psychotherapy, University Hospital of the Technische Universitat Munchen, Germany. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Sciences, University of Milan, and IRCSS Multimedica Sesto S Giovanni, Milan, Italy. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University, Taipei, Taiwan. FAU - de Groot, Eric AU - de Groot E AD - Academic Medical Centre, Cardiology and Thoracic Surgery, and Imagelabonline and Cardiovascular, Amsterdam, The Netherlands. FAU - Empana, Jean-Philippe AU - Empana JP AD - INSERM, U970, Universite Paris Descartes, France. FAU - Etgen, Thorleif AU - Etgen T AD - Department of Neurology, Kliniken Sudostbayern, Klinikum Traunstein, Germany. FAU - Franco, Oscar H AU - Franco OH AD - Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands. FAU - Iglseder, Bernhard AU - Iglseder B AD - Department of Geriatric Medicine, Paracelsus Medical University, and the Gemeinnutzige Salzburger Landeskliniken Betriebsgesellschaft GmbH, Christian-Doppler-Klinik, Salzburg, Austria. FAU - Johnsen, Stein H AU - Johnsen SH AD - Department of Neurology and Neurophysiology, University Hospital of Northern Norway, and the Department of Clinical Medicine, University of Tromso, Tromso, Norway. FAU - Kavousi, Maryam AU - Kavousi M AD - Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands. FAU - Lind, Lars AU - Lind L AD - Department of Medicine, Uppsala University, Sweden. FAU - Liu, Jing AU - Liu J AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China. FAU - Mathiesen, Ellisiv B AU - Mathiesen EB AD - Department of Neurology and Neurophysiology, University Hospital of Northern Norway, and the Department of Clinical Medicine, University of Tromso, Tromso, Norway. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, and the SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Olsen, Michael H AU - Olsen MH AD - Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital, Denmark. FAU - Papagianni, Aikaterini AU - Papagianni A AD - Department of Nephrology, Aristotle University of Thessaloniki, Hippokration General Hospital, Greece. FAU - Poppert, Holger AU - Poppert H AD - Department of Neurology, University Hospital of the Technische Universitat Munchen, Germany. FAU - Price, Jackie F AU - Price JF AD - Centre for Population Health Sciences, University of Edinburgh, UK. FAU - Sacco, Ralph L AU - Sacco RL AD - Department of Neurology, Miller School of Medicine, University of Miami, FL, USA. FAU - Yanez, David N AU - Yanez DN AD - Department of Biostatistics, University of Washington, Seattle, WA, USA. FAU - Zhao, Dong AU - Zhao D AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China. FAU - Schminke, Ulf AU - Schminke U AD - Department of Neurology, Greifswald University Clinic, Germany. FAU - Bulbul, Alpaslan AU - Bulbul A AD - Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany. FAU - Polak, Joseph F AU - Polak JF AD - Tufts University School of Medicine, Tufts Medical Center, Boston, MA, USA. FAU - Sitzer, Matthias AU - Sitzer M AD - Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany Department of Neurology, Klinikum Herford, Germany. FAU - Hofman, Albert AU - Hofman A AD - Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. FAU - Grigore, Liliana AU - Grigore L AD - Department of Pharmacological Sciences, University of Milan, and the SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Dorr, Marcus AU - Dorr M AD - Department B for Internal Medicine, University Medicine Greifswald, and the German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Germany. FAU - Su, Ta-Chen AU - Su TC AD - Department of Internal Medicine, National Taiwan University, Taipei, Taiwan. FAU - Ducimetiere, Pierre AU - Ducimetiere P AD - University Paris Sud-XI, Kremlin-Bicetre, France. FAU - Xie, Wuxiang AU - Xie W AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China. FAU - Ronkainen, Kimmo AU - Ronkainen K AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Rundek, Tatjana AU - Rundek T AD - Department of Neurology, Miller School of Medicine, University of Miami, FL, USA. FAU - Robertson, Christine AU - Robertson C AD - Centre for Population Health Sciences, University of Edinburgh, UK. FAU - Fagerberg, Bjorn AU - Fagerberg B AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden. FAU - Bokemark, Lena AU - Bokemark L AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden. FAU - Steinmetz, Helmuth AU - Steinmetz H AD - Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany. FAU - Ikram, M Arfan AU - Ikram MA AD - Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands. FAU - Volzke, Henry AU - Volzke H AD - Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, Greifswald, Germany. FAU - Lin, Hung-Ju AU - Lin HJ AD - Department of Internal Medicine, National Taiwan University, Taipei, Taiwan Health Management Centre, National Taiwan University Hospital, Taipei, Taiwan. FAU - Plichart, Matthieu AU - Plichart M AD - INSERM, U970, Universite Paris Descartes, France Gerontology Department, Broca Hospital, Paris, France. FAU - Tuomainen, Tomi-Pekka AU - Tuomainen TP AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Desvarieux, Moise AU - Desvarieux M AD - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA, and the Ecole des Hautes Etudes en Sante Publique, and INSERM U738, Paris, France. FAU - McLachlan, Stela AU - McLachlan S AD - Centre for Population Health Sciences, University of Edinburgh, UK. FAU - Schmidt, Caroline AU - Schmidt C AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden. FAU - Kauhanen, Jussi AU - Kauhanen J AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Willeit, Johann AU - Willeit J AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Lorenz, Matthias W AU - Lorenz MW AD - Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany. FAU - Sander, Dirk AU - Sander D AD - Department of Neurology, Benedictus Krankenhaus Tutzing and Feldafing, Tutzing, Germany and Technische Universitat Munchen, Germany D.Sander@mac.com. CN - PROG-IMT study group LA - eng GR - N01HC85084/HC/NHLBI NIH HHS/United States GR - N01HC85080/HC/NHLBI NIH HHS/United States GR - U01 HL080295/HL/NHLBI NIH HHS/United States GR - R01 DE013094/DE/NIDCR NIH HHS/United States GR - HHSN268200800007C/HL/NHLBI NIH HHS/United States GR - RG/08/014/24067/British Heart Foundation/United Kingdom GR - N01HC85085/HC/NHLBI NIH HHS/United States GR - N01 HC085085/HC/NHLBI NIH HHS/United States GR - N01HC55222/HL/NHLBI NIH HHS/United States GR - MR/L003120/1/Medical Research Council/United Kingdom GR - N01HC85086/HL/NHLBI NIH HHS/United States GR - N01HC45133/HC/NHLBI NIH HHS/United States GR - R37 NS029993/NS/NINDS NIH HHS/United States GR - N01HC85081/HC/NHLBI NIH HHS/United States GR - N01HC85079/HC/NHLBI NIH HHS/United States GR - HHSN268201200036C/HL/NHLBI NIH HHS/United States GR - R37 NS 029993/NS/NINDS NIH HHS/United States GR - N01HC85086/HC/NHLBI NIH HHS/United States GR - R01 HL080295/HL/NHLBI NIH HHS/United States GR - N01HC85082/HC/NHLBI NIH HHS/United States GR - N01 HC085084/HC/NHLBI NIH HHS/United States GR - HHSN268200800007C/PHS HHS/United States GR - N01HC85082/HL/NHLBI NIH HHS/United States GR - N01HC85083/HL/NHLBI NIH HHS/United States GR - HHSN268201200036C/PHS HHS/United States GR - HL080295/HL/NHLBI NIH HHS/United States GR - N01HC85083/HC/NHLBI NIH HHS/United States GR - N01HC85079/HL/NHLBI NIH HHS/United States GR - R01 AG023629/AG/NIA NIH HHS/United States GR - N01HC35129/HC/NHLBI NIH HHS/United States GR - N01 HC045133/HC/NHLBI NIH HHS/United States GR - N01HC85080/HL/NHLBI NIH HHS/United States GR - AG023629/AG/NIA NIH HHS/United States GR - N01 HC035129/HC/NHLBI NIH HHS/United States GR - R56 AG023629/AG/NIA NIH HHS/United States GR - N01HC85081/HL/NHLBI NIH HHS/United States GR - N01 HC55222/HC/NHLBI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141121 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Biomarkers) RN - 9001-32-5 (Fibrinogen) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Atherosclerosis/*blood MH - Biomarkers/blood MH - C-Reactive Protein/*analysis MH - Carotid Intima-Media Thickness MH - *Disease Progression MH - Fibrinogen/*analysis MH - Humans MH - Inflammation/blood MH - *Leukocyte Count PMC - PMC4544641 MID - NIHMS710968 OTO - NOTNLM OT - Inflammation OT - atherosclerosis OT - meta-analysis EDAT- 2014/11/25 06:00 MHDA- 2016/11/04 06:00 CRDT- 2014/11/23 06:00 PHST- 2014/09/11 00:00 [received] PHST- 2014/10/31 00:00 [accepted] PHST- 2014/11/23 06:00 [entrez] PHST- 2014/11/25 06:00 [pubmed] PHST- 2016/11/04 06:00 [medline] AID - 2047487314560664 [pii] AID - 10.1177/2047487314560664 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2016 Jan;23(2):194-205. doi: 10.1177/2047487314560664. Epub 2014 Nov 21. PMID- 27910077 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20170817 IS - 1897-4279 (Electronic) IS - 0022-9032 (Linking) VI - 74 IP - 11 DP - 2016 TI - [2016 ESC/EAS Guidelines for the Management of Dyslipidaemias]. PG - 1234-1318 LID - 10.5603/KP.2016.0157 [doi] FAU - Catapano, Alberico L AU - Catapano AL AD - alberico.catapano@unimi.it. FAU - Graham, Ian AU - Graham I FAU - De Backer, Guy AU - De Backer G FAU - Wiklund, Olov AU - Wiklund O FAU - Chapman, M John AU - Chapman MJ FAU - Drexel, Heinz AU - Drexel H FAU - Hoes, Arno W AU - Hoes AW FAU - Jennings, Catriona S AU - Jennings CS FAU - Landmesser, Ulf AU - Landmesser U FAU - Pedersen, Terje R AU - Pedersen TR FAU - Reiner, Zeljko AU - Reiner Z FAU - Riccardi, Gabriele AU - Riccardi G FAU - Taskinen, Marja-Riita AU - Taskinen MR FAU - Tokgozoglu, Lale AU - Tokgozoglu L FAU - Verschuren, W M Monique AU - Verschuren WM FAU - Vlachopoulos, Charalambos AU - Vlachopoulos C FAU - Wood, David A AU - Wood DA FAU - Zamorano, Jose Luis AU - Zamorano JL LA - pol PT - Journal Article PT - Practice Guideline TT - Wytyczne ESC/EAS dotyczace leczenia zaburzen lipidowych w 2016 roku. PL - Poland TA - Kardiol Pol JT - Kardiologia polska JID - 0376352 SB - IM MH - Cardiology MH - Cardiovascular Diseases/etiology/*prevention & control MH - Dyslipidemias/complications/diet therapy/*drug therapy MH - Europe MH - Female MH - Humans MH - Male MH - Societies, Medical EDAT- 2016/12/03 06:00 MHDA- 2017/04/30 06:00 CRDT- 2016/12/03 06:00 PHST- 2016/11/22 00:00 [received] PHST- 2016/12/03 06:00 [entrez] PHST- 2016/12/03 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] AID - VM/OJS/KP/11036 [pii] AID - 10.5603/KP.2016.0157 [doi] PST - ppublish SO - Kardiol Pol. 2016;74(11):1234-1318. doi: 10.5603/KP.2016.0157. PMID- 27654471 OWN - NLM STAT- MEDLINE DCOM- 20170605 LR - 20170817 IS - 1897-4279 (Electronic) IS - 0022-9032 (Linking) VI - 74 IP - 9 DP - 2016 TI - [2016 European Guidelines on cardiovascular disease prevention in clinical practice]. PG - 821-936 LID - 10.5603/KP.2016.0120 [doi] FAU - Piepoli, Massimo F AU - Piepoli MF AD - Heart Failure Unit, Cardiology Department, Polichirurgico Hospital G. Da Saliceto, Cantone Del Cristo, 29121 Piacenza, Emilia Romagna, Italy. m.piepoli@alice.it. FAU - Hoes, Arno W AU - Hoes AW FAU - Agewall, Stefan AU - Agewall S FAU - Albus, Christian AU - Albus C FAU - Brotons, Carlos AU - Brotons C FAU - Catapano, Alberico L AU - Catapano AL FAU - Cooney, Marie- Therese AU - Cooney M FAU - Corra, Ugo AU - Corra U FAU - Cosyns, Bernard AU - Cosyns B FAU - Deaton, Christi AU - Deaton C FAU - Graham, Ian AU - Graham I FAU - Hall, Michael Stephen AU - Hall MS FAU - Hobbs, F D Richard AU - Hobbs FD FAU - Lochen, Maja-Lisa AU - Lochen ML FAU - Lollgen, Herbert AU - Lollgen H FAU - Marques-Vidal, Pedro AU - Marques-Vidal P FAU - Perk, Joep AU - Perk J FAU - Prescott, Eva AU - Prescott E FAU - Redon, Josep AU - Redon J FAU - Richter, Dimitrios J AU - Richter DJ FAU - Sattar, Naveed AU - Sattar N FAU - Smulders, Yvo AU - Smulders Y FAU - Tiberi, Monica AU - Tiberi M FAU - van der Worp, H Bart AU - van der Worp HB FAU - van Dis, Ineke AU - van Dis I FAU - Verschuren, W M Monique AU - Verschuren WM FAU - Binno, Simone AU - Binno S LA - pol PT - Journal Article PT - Practice Guideline TT - Wytyczne ESC dotyczace prewencji chorob ukladu sercowo-naczyniowego w praktyce klinicznej w 2016 roku. PL - Poland TA - Kardiol Pol JT - Kardiologia polska JID - 0376352 SB - IM MH - *Cardiology MH - Cardiovascular Diseases/*prevention & control MH - Europe MH - Female MH - Humans MH - Male MH - *Societies, Medical EDAT- 2016/09/23 06:00 MHDA- 2017/06/06 06:00 CRDT- 2016/09/23 06:00 PHST- 2016/09/07 00:00 [received] PHST- 2016/09/23 06:00 [entrez] PHST- 2016/09/23 06:00 [pubmed] PHST- 2017/06/06 06:00 [medline] AID - VM/OJS/KP/10860 [pii] AID - 10.5603/KP.2016.0120 [doi] PST - ppublish SO - Kardiol Pol. 2016;74(9):821-936. doi: 10.5603/KP.2016.0120. PMID- 26646793 OWN - NLM STAT- MEDLINE DCOM- 20161007 LR - 20190225 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 40 DP - 2015 Dec 15 TI - Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk. PG - 42468-77 LID - 10.18632/oncotarget.6468 [doi] AB - Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis. FAU - Walsh, Kyle M AU - Walsh KM AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. AD - Program in Neurologic Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA. FAU - Codd, Veryan AU - Codd V AD - Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. AD - National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. FAU - Rice, Terri AU - Rice T AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Nelson, Christopher P AU - Nelson CP AD - Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. AD - National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. FAU - Smirnov, Ivan V AU - Smirnov IV AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - McCoy, Lucie S AU - McCoy LS AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Hansen, Helen M AU - Hansen HM AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Elhauge, Edward AU - Elhauge E AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Ojha, Juhi AU - Ojha J AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Francis, Stephen S AU - Francis SS AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Madsen, Nils R AU - Madsen NR AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Bracci, Paige M AU - Bracci PM AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco , California, USA. FAU - Pico, Alexander R AU - Pico AR AD - Gladstone Institutes, San Francisco, California, USA. FAU - Molinaro, Annette M AU - Molinaro AM AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Tihan, Tarik AU - Tihan T AD - Department of Pathology, University of California, San Francisco, San Francisco, California, USA. FAU - Berger, Mitchel S AU - Berger MS AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Chang, Susan M AU - Chang SM AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Prados, Michael D AU - Prados MD AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Jenkins, Robert B AU - Jenkins RB AD - Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Wiemels, Joseph L AU - Wiemels JL AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco , California, USA. AD - Institute for Human Genetics, University of California, San Francisco, San Francisco , California, USA. CN - ENGAGE Consortium Telomere Group FAU - Samani, Nilesh J AU - Samani NJ AD - Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. AD - National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. FAU - Wiencke, John K AU - Wiencke JK AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. AD - Institute for Human Genetics, University of California, San Francisco, San Francisco , California, USA. FAU - Wrensch, Margaret R AU - Wrensch MR AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. AD - Institute for Human Genetics, University of California, San Francisco, San Francisco , California, USA. LA - eng GR - R01 CA139020/CA/NCI NIH HHS/United States GR - HHSN261201000034C/PHS HHS/United States GR - R01CA126831/CA/NCI NIH HHS/United States GR - British Heart Foundation/United Kingdom GR - U58DP003862-01/DP/NCCDPHP CDC HHS/United States GR - HHSN261201000140C/CA/NCI NIH HHS/United States GR - P50 CA108961/CA/NCI NIH HHS/United States GR - HHSN261201000035C/CA/NCI NIH HHS/United States GR - T32 CA151022/CA/NCI NIH HHS/United States GR - RC1 NS068222/NS/NINDS NIH HHS/United States GR - RC1NS068222Z/NS/NINDS NIH HHS/United States GR - R25 CA112355/CA/NCI NIH HHS/United States GR - HHSN261201000035C/PHS HHS/United States GR - R01 CA126831/CA/NCI NIH HHS/United States GR - UL1 RR024131/RR/NCRR NIH HHS/United States GR - 076113/Wellcome Trust/United Kingdom GR - MR/M012816/1/Medical Research Council/United Kingdom GR - 085475/Wellcome Trust/United Kingdom GR - P50 CA097257/CA/NCI NIH HHS/United States GR - R25CA112355/CA/NCI NIH HHS/United States GR - P30 CA015083/CA/NCI NIH HHS/United States GR - HHSN261201000035I/CA/NCI NIH HHS/United States GR - P50CA097257/CA/NCI NIH HHS/United States GR - HHSN261201000034C/CA/NCI NIH HHS/United States GR - P50CA108961/CA/NCI NIH HHS/United States GR - P30CA15083/CA/NCI NIH HHS/United States GR - R01CA139020/CA/NCI NIH HHS/United States GR - R01CA52689/CA/NCI NIH HHS/United States GR - U58 DP003862/DP/NCCDPHP CDC HHS/United States GR - HHSN261201000140C/PHS HHS/United States GR - R01 CA052689/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 SB - IM MH - Adult MH - Brain Neoplasms/*genetics MH - Case-Control Studies MH - Female MH - Genetic Predisposition to Disease/*genetics MH - Genome-Wide Association Study MH - Genotype MH - Glioma/*genetics MH - Humans MH - Leukocytes/*metabolism MH - Male MH - Models, Statistical MH - Polymorphism, Single Nucleotide MH - Risk Factors MH - Telomere/*genetics PMC - PMC4767445 OTO - NOTNLM OT - CST complex OT - glioma OT - single nucleotide polymorphism OT - telomerase OT - telomere IR - Codd V FIR - Codd, Veryan IR - Nelson CP FIR - Nelson, Christopher P IR - Albrecht E FIR - Albrecht, Eva IR - Mangino M FIR - Mangino, Massimo IR - Deelen J FIR - Deelen, Joris IR - Buxton JL FIR - Buxton, Jessica L IR - Hottenga JJ FIR - Hottenga, Jouke Jan IR - Fischer K FIR - Fischer, Krista IR - Esko T FIR - Esko, Tonu IR - Surakka I FIR - Surakka, Ida IR - Broer L FIR - Broer, Linda IR - Nyholt DR FIR - Nyholt, Dale R IR - Mateo Leach I FIR - Mateo Leach, Irene IR - Salo P FIR - Salo, Perttu IR - Hagg S FIR - Hagg, Sara IR - Matthews MK FIR - Matthews, Mary K IR - Palmen J FIR - Palmen, Jutta IR - Norata GD FIR - Norata, Giuseppe D IR - O'Reilly PF FIR - O'Reilly, Paul F IR - Saleheen D FIR - Saleheen, Danish IR - Amin N FIR - Amin, Najaf IR - Balmforth AJ FIR - Balmforth, Anthony J IR - Beekman M FIR - Beekman, Marian IR - de Boer RA FIR - de Boer, Rudolf A IR - Bohringer S FIR - Bohringer, Stefan IR - Braund PS FIR - Braund, Peter S IR - Burton PR FIR - Burton, Paul R IR - de Craen AJ FIR - de Craen, Anton J M IR - Denniff M FIR - Denniff, Matthew IR - Dong Y FIR - Dong, Yanbin IR - Douroudis K FIR - Douroudis, Konstantinos IR - Dubinina E FIR - Dubinina, Elena IR - Eriksson JG FIR - Eriksson, Johan G IR - Garlaschelli K FIR - Garlaschelli, Katia IR - Guo D FIR - Guo, Dehuang IR - Hartikainen AL FIR - Hartikainen, Anna-Liisa IR - Henders AK FIR - Henders, Anjali K IR - Houwing-Duistermaat JJ FIR - Houwing-Duistermaat, Jeanine J IR - Kananen L FIR - Kananen, Laura IR - Karssen LC FIR - Karssen, Lennart C IR - Kettunen J FIR - Kettunen, Johannes IR - Klopp N FIR - Klopp, Norman IR - Lagou V FIR - Lagou, Vasiliki IR - van Leeuwen EM FIR - van Leeuwen, Elisabeth M IR - Madden PA FIR - Madden, Pamela A IR - Magi R FIR - Magi, Reedik IR - Magnusson PK FIR - Magnusson, Patrik K E IR - Mannisto S FIR - Mannisto, Satu IR - McCarthy MI FIR - McCarthy, Mark I IR - Medland SE FIR - Medland, Sarah E IR - Mihailov E FIR - Mihailov, Evelin IR - Montgomery GW FIR - Montgomery, Grant W IR - Oostra BA FIR - Oostra, Ben A IR - Palotie A FIR - Palotie, Aarno IR - Peters A FIR - Peters, Annette IR - Pollard H FIR - Pollard, Helen IR - Pouta A FIR - Pouta, Anneli IR - Prokopenko I FIR - Prokopenko, Inga IR - Ripatti S FIR - Ripatti, Samuli IR - Salomaa V FIR - Salomaa, Veikko IR - Suchiman H FIR - Suchiman, H Eka D IR - Valdes AM FIR - Valdes, Ana M IR - Verweij N FIR - Verweij, Niek IR - Vinuela A FIR - Vinuela, Ana IR - Wang X FIR - Wang, Xiaoling IR - Wichmann HE FIR - Wichmann, H-Erich IR - Widen E FIR - Widen, Elisabeth IR - Willemsen G FIR - Willemsen, Gonneke IR - Wright MJ FIR - Wright, Margaret J IR - Xia K FIR - Xia, Kai IR - Xiao X FIR - Xiao, Xiangjun IR - van Veldhuisen DJ FIR - van Veldhuisen, Dirk J IR - Catapano AL FIR - Catapano, Alberico L IR - Tobin MD FIR - Tobin, Martin D IR - Hall AS FIR - Hall, Alistair S IR - Blakemore AI FIR - Blakemore, Alexandra I F IR - van Gilst WH FIR - van Gilst, Wiek H IR - Zhu H FIR - Zhu, Haidong IR - Erdmann J FIR - Erdmann, Jeanette IR - Reilly MP FIR - Reilly, Muredach P IR - Kathiresan S FIR - Kathiresan, Sekar IR - Schunkert H FIR - Schunkert, Heribert IR - Talmud PJ FIR - Talmud, Philippa J IR - Pedersen NL FIR - Pedersen, Nancy L IR - Perola M FIR - Perola, Markus IR - Ouwehand W FIR - Ouwehand, Willem IR - Kaprio J FIR - Kaprio, Jaakko IR - Martin NG FIR - Martin, Nicholas G IR - van Duijn CM FIR - van Duijn, Cornelia M IR - Hovatta I FIR - Hovatta, Iiris IR - Gieger C FIR - Gieger, Christian IR - Metspalu A FIR - Metspalu, Andres IR - Boomsma DI FIR - Boomsma, Dorret I IR - Jarvelin MR FIR - Jarvelin, Marjo-Riitta IR - Slagboom P FIR - Slagboom, P Eline IR - Thompson JR FIR - Thompson, John R IR - Spector TD FIR - Spector, Tim D IR - van der Harst P FIR - van der Harst, Pim IR - Samani NJ FIR - Samani, Nilesh J EDAT- 2015/12/10 06:00 MHDA- 2016/10/08 06:00 CRDT- 2015/12/10 06:00 PHST- 2015/11/15 00:00 [received] PHST- 2015/11/23 00:00 [accepted] PHST- 2015/12/10 06:00 [entrez] PHST- 2015/12/10 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] AID - 6468 [pii] AID - 10.18632/oncotarget.6468 [doi] PST - ppublish SO - Oncotarget. 2015 Dec 15;6(40):42468-77. doi: 10.18632/oncotarget.6468. PMID- 26671304 OWN - NLM STAT- MEDLINE DCOM- 20160922 LR - 20151216 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 20 DP - 2015 Dec TI - Think Again About Cholesterol Survey. PG - 1-5 LID - 10.1016/S1567-5688(15)30011-8 [doi] LID - S1567-5688(15)30011-8 [pii] AB - Cardiovascular disease (CVD) is still the main cause of death in Europe. Elevated plasma cholesterol, specifically low-density lipoprotein cholesterol (LDL-C), is the main causative risk factor for CVD, most prominently associated with coronary heart disease. A widespread disinformation about cholesterol and CVD is one factor underlying a poor compliance to lipid-lowering therapy. To investigate how cholesterol, CVD and cholesterol reduction is perceived in the population, a survey was commissioned by the European Atherosclerosis Society (EAS). Nearly half of people above 25 years of age are most worried about cancer (45%), compared to just over one in four who are worried about heart disease (27%). A majority believe being overweight (72%), blood pressure (70%) and smoking (67%) most affect heart health, far more than note cholesterol (59%) and family history (39%). The majority of adults recognize that high LDL (or "bad") cholesterol should be a health priority for everyone, including those younger than 40 and those who are not overweight. However, 1 in 4 (25%) incorrectly believe that it does not need to be a concern until someone shows signs or symptoms. Although 89% of adults surveyed agreed it is important for people to know whether or not they have high LDL-C, an overwhelming 92% did not know their LDL-C levels or had never had their cholesterol levels tested. A high 63% had never heard of familial hypercholesterolemia: France had the lowest level of awareness (41%) to Denmark with a high 80%, and the association of the disease with high levels of LDL-C is quite poor (only 36%), with Sweden only at 22% versus a high in Spain of 54%. A large part of the people participating in the survey were quite uncertain about the modality of transmission for familial hypercholesterolemia in the family. All in all, this survey highlights the need for more information among citizens for the role of cholesterol in determining CVD. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Wiklund, Olov AU - Wiklund O AD - Sahlgrenska Academy, University of Gothenburg, Sweden. CN - European Atherosclerosis Society LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20151207 PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adult MH - Aged MH - Cardiovascular Diseases/blood/*epidemiology/etiology MH - Cholesterol/*blood MH - Female MH - Humans MH - Hypercholesterolemia/*blood/complications/epidemiology MH - Male MH - Middle Aged MH - Morbidity/trends MH - Prognosis MH - Retrospective Studies MH - Risk Assessment/*methods MH - Risk Factors MH - *Surveys and Questionnaires OTO - NOTNLM OT - Cholesterol OT - familial OT - high-density lipoprotein OT - hypercholesterolemia OT - low-density lipoprotein EDAT- 2015/12/17 06:00 MHDA- 2016/09/23 06:00 CRDT- 2015/12/17 06:00 PHST- 2015/12/17 06:00 [entrez] PHST- 2015/12/17 06:00 [pubmed] PHST- 2016/09/23 06:00 [medline] AID - S1567-5688(15)30011-8 [pii] AID - 10.1016/S1567-5688(15)30011-8 [doi] PST - ppublish SO - Atheroscler Suppl. 2015 Dec;20:1-5. doi: 10.1016/S1567-5688(15)30011-8. Epub 2015 Dec 7. PMID- 26520899 OWN - NLM STAT- MEDLINE DCOM- 20160914 LR - 20151128 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 243 IP - 2 DP - 2015 Dec TI - Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. PG - 449-61 LID - 10.1016/j.atherosclerosis.2015.09.032 [doi] LID - S0021-9150(15)30141-6 [pii] AB - Berberine (BBR) is an isoquinoline plant alkaloid endowed with several pharmacological activities, including anti-microbial, glucose- and cholesterol-lowering, anti-tumoral and immunomodulatory properties. The main mechanism by which BBR exerts a protective role in atherosclerosis relates to its cholesterol-lowering activity. BBR significantly increases hepatic low density lipoprotein receptor (LDLR) expression and reduces the expression and secretion of the LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9). In addition to this, several other atheroprotective effects have been ascribed to BBR, including anti-inflammatory and anti-oxidant properties, inhibition of vascular smooth muscle cell proliferation and improvement of endothelial dysfunction. BBR also increases glucose utilization in adipocytes and myocytes, while decreases glucose absorption in intestinal cells, resulting in a net hypoglycemic effect. In hypercholesterolemic animals, BBR significantly decreases LDL-C and total cholesterol (TC) levels and reduces aortic lesions, an effect similar to that of statins. In diabetic animals, BBR significantly reduces glucose levels, improves glucose tolerance, reduces body weight gain and adipose tissue mass. Several clinical studies have also tested the efficacy of BBR in humans. In hypercholesterolemic subjects, BBR induces a significant reduction of TC, triglycerides and LDL-C levels and a significant increase of HDL-C levels, without major adverse effects. BBR also reduces glycemia and plasma cholesterol in diabetic patients, improves lipid and glucose profile and decreases body mass index and waist circumference in subjects with metabolic syndrome. These findings, together with the good tolerability, suggest that BBR administration might be considered a potential therapeutic approach for the treatment of hypercholesterolemia or diabetes. Given the level of evidence available to date well-designed randomized controlled trials to test safety and efficacy of BBR are warranted. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; IRCCS MultiMedica, Milan, Italy. Electronic address: angela.pirillo@guest.unimi.it. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS MultiMedica, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20150930 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Anticholesteremic Agents) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0I8Y3P32UF (Berberine) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Anticholesteremic Agents/adverse effects/*therapeutic use MH - Berberine/adverse effects/*therapeutic use MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Cholesterol/*blood MH - Diabetes Mellitus/blood/diagnosis/*drug therapy MH - Disease Models, Animal MH - Humans MH - Hypercholesterolemia/blood/diagnosis/*drug therapy MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - AMP-activated protein kinase OT - Berberine OT - Glucose-lowering OT - LDL receptor OT - Lipid-lowering EDAT- 2015/11/02 06:00 MHDA- 2016/09/15 06:00 CRDT- 2015/11/02 06:00 PHST- 2015/06/17 00:00 [received] PHST- 2015/09/01 00:00 [revised] PHST- 2015/09/24 00:00 [accepted] PHST- 2015/11/02 06:00 [entrez] PHST- 2015/11/02 06:00 [pubmed] PHST- 2016/09/15 06:00 [medline] AID - S0021-9150(15)30141-6 [pii] AID - 10.1016/j.atherosclerosis.2015.09.032 [doi] PST - ppublish SO - Atherosclerosis. 2015 Dec;243(2):449-61. doi: 10.1016/j.atherosclerosis.2015.09.032. Epub 2015 Sep 30. PMID- 26408930 OWN - NLM STAT- MEDLINE DCOM- 20160914 LR - 20151018 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 243 IP - 1 DP - 2015 Nov TI - Familial hypercholesterolaemia: A global call to arms. PG - 257-9 LID - 10.1016/j.atherosclerosis.2015.09.021 [doi] LID - S0021-9150(15)30130-1 [pii] FAU - Vallejo-Vaz, Antonio J AU - Vallejo-Vaz AJ AD - School of Public Health, Imperial College London, London, UK. FAU - Kondapally Seshasai, Sreenivasa Rao AU - Kondapally Seshasai SR AD - Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, UK. FAU - Cole, Della AU - Cole D AD - Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, UK. FAU - Hovingh, G Kees AU - Hovingh GK AD - Academic Medical Centre, Amsterdam, The Netherlands. FAU - Kastelein, John J P AU - Kastelein JJ AD - Academic Medical Centre, Amsterdam, The Netherlands. FAU - Mata, Pedro AU - Mata P AD - Fundacion Hipercolesterolemia Familiar, Madrid, Spain. FAU - Raal, Frederick J AU - Raal FJ AD - Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Santos, Raul D AU - Santos RD AD - Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. FAU - Soran, Handrean AU - Soran H AD - Faculty of Medical and Health Sciences, University of Manchester, Manchester, UK. FAU - Watts, Gerald F AU - Watts GF AD - Cardiovascular Medicine, Royal Perth Hospital, University of Western Australia, Perth, Australia. FAU - Abifadel, Marianne AU - Abifadel M AD - Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Saint-Joseph University, Beirut, Lebanon. FAU - Aguilar-Salinas, Carlos A AU - Aguilar-Salinas CA AD - Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico. FAU - Akram, Asif AU - Akram A AD - Global eHealth Unit, School of Public Health, Imperial College London, London, UK. FAU - Alnouri, Fahad AU - Alnouri F AD - Cardiovascular Prevention and Rehabilitation Unit, Prince Sultan Cardiac Centre Riyadh, Riyadh, Saudi Arabia. FAU - Alonso, Rodrigo AU - Alonso R AD - Lipid Clinic, Department of Nutrition, Clinica Las Condes, Santiago de Chile, Chile. FAU - Al-Rasadi, Khalid AU - Al-Rasadi K AD - Sultan Qaboos University Hospital, Muscat, Oman. FAU - Banach, Maciej AU - Banach M AD - Department of Hypertension, Medical University of Lodz, Lodz, Poland. FAU - Bogsrud, Martin P AU - Bogsrud MP AD - National Advisory Unit on Familial Hypercholesterolemia, Norway. FAU - Bourbon, Mafalda AU - Bourbon M AD - Instituto Nacional de Saude Doutor Ricardo Jorge and BioISI - Biosystems & Integrative Sciences Institute, Universidade de Lisboa, Portugal. FAU - Bruckert, Eric AU - Bruckert E AD - Endocrinologie metabolisme et prevention cardiovasculaire, Institut E3M et IHU cardiometabolique (ICAN), HopitalPitieSalpetriere, Paris, France. FAU - Car, Josip AU - Car J AD - Global eHealth Unit, School of Public Health, Imperial College London, London, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. FAU - Corral, Pablo AU - Corral P AD - FASTA University, School of Medicine, Mar del Plata, Argentina. FAU - Descamps, Olivier AU - Descamps O AD - Hopital de Jolimont, Haine Saint-Paul, Belgium. FAU - Dieplinger, Hans AU - Dieplinger H AD - Austrian Atherosclerosis Society, c/o, Medical University of Innsbruck, Innsbruck, Austria. FAU - Durst, Ronen AU - Durst R AD - Hadassah Hebrew University Medical Center, Jerusalem, Israel. FAU - Freiberger, Tomas AU - Freiberger T AD - Centre for Cardiovascular Surgery and Transplantation Brno, and Ceitec, Masaryk University, Brno, Czech Republic. FAU - Gaspar, Isabel M AU - Gaspar IM AD - Medical Genetics Department, Centro Hospitalar de Lisboa Ocidental and Genetics Laboratory, Lisbon Medical School, University of Lisbon, Portugal. FAU - Genest, Jaques AU - Genest J AD - McGill University, Montreal, Canada. FAU - Harada-Shiba, Mariko AU - Harada-Shiba M AD - National Cerebral and Cardiovascular Centre Research Institute, Osaka, Japan. FAU - Jiang, Lixin AU - Jiang L AD - National Center for Cardiovascular Diseases, Beijing, China. FAU - Kayikcioglu, Meral AU - Kayikcioglu M AD - Ege University Medical School, Department of Cardiology, Izmir, Turkey. FAU - Lam, Carolyn S P AU - Lam CS AD - National Heart Centre Singapore and Duke-National University of Singapore, Singapore. FAU - Latkovskis, Gustavs AU - Latkovskis G AD - Paul Stradins Clinical University Hospital, Latvian Research Institute of Cardiology, University of Latvia, Riga, Latvia. FAU - Laufs, Ulrich AU - Laufs U AD - Universitat des Saarlandes, Homburg, Germany. FAU - Liberopoulos, Evangelos AU - Liberopoulos E AD - University of Ioannina Medical School, Ioannina, Greece. FAU - Nilsson, Lennart AU - Nilsson L AD - Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark. FAU - O'Donoghue, John M AU - O'Donoghue JM AD - Global eHealth Unit, School of Public Health, Imperial College London, London, UK. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Schunkert, Heribert AU - Schunkert H AD - Deutsches Herzzentrum Munchen, Klinikan der TU Munchen, Munich Heart Alliance, Germany. FAU - Shehab, Abdulla AU - Shehab A AD - CMHS, UAE University, AlAin, United Arab Emirates. FAU - Stoll, Mario AU - Stoll M AD - Cardiovascular Genetic Laboratory, Cardiovascular Health Commission, Montevideo, Uruguay. FAU - Su, Ta-Chen AU - Su TC AD - Department of Internal Medicine and Cardiovascular Centre, National Taiwan University Hospital, Taipei, Taiwan. FAU - Susekov, Andrey AU - Susekov A AD - Laboratory of Clinical Lipidology, Cardiology Research Complex, Moscow, Russia. FAU - Widen, Elisabeth AU - Widen E AD - Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan and Multimedica IRCCS Milan, Italy. FAU - Ray, Kausik K AU - Ray KK AD - School of Public Health, Imperial College London, London, UK. Electronic address: k.ray@imperial.ac.uk. LA - eng PT - Journal Article DEP - 20150918 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Receptors, LDL) SB - IM MH - Europe MH - Global Health MH - Heterozygote MH - Humans MH - Hyperlipoproteinemia Type II/*epidemiology/genetics/prevention & control/*therapy MH - Mutation MH - Receptors, LDL/genetics MH - Societies, Medical OTO - NOTNLM OT - Familial hypercholesterolaemia EDAT- 2015/09/27 06:00 MHDA- 2016/09/15 06:00 CRDT- 2015/09/27 06:00 PHST- 2015/09/14 00:00 [received] PHST- 2015/09/14 00:00 [accepted] PHST- 2015/09/27 06:00 [entrez] PHST- 2015/09/27 06:00 [pubmed] PHST- 2016/09/15 06:00 [medline] AID - S0021-9150(15)30130-1 [pii] AID - 10.1016/j.atherosclerosis.2015.09.021 [doi] PST - ppublish SO - Atherosclerosis. 2015 Nov;243(1):257-9. doi: 10.1016/j.atherosclerosis.2015.09.021. Epub 2015 Sep 18. PMID- 26532264 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160204 LR - 20160519 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 18 IP - 7 DP - 2015 Nov TI - Real-World Identification Of European Patients With Statin-Associated Symptoms: Clinical Practice Compared With Clinical Guidelines. PG - A401 LID - 10.1016/j.jval.2015.09.923 [doi] LID - S1098-3015(15)02999-X [pii] FAU - Hovingh, G K AU - Hovingh GK AD - Academic Medical Center, Amsterdam, The Netherlands. FAU - Gandra, S R AU - Gandra SR AD - Amgen, Inc., Thousand Oaks, CA, USA. FAU - McKendrick, J AU - McKendrick J AD - PRMA Consulting, Hampshire, UK. FAU - Dent, R AU - Dent R AD - Amgen, Inc., Thousand Oaks, CA, USA. FAU - Wieffer, H M AU - Wieffer HM AD - PRMA Consulting, Fleet, UK. FAU - Catapano, A L AU - Catapano AL AD - University of Milan, Milan, Italy. FAU - Oh, P AU - Oh P AD - Toronto Rehabilitation Institute, Toronto, ON, Canada. FAU - Rosenson, R S AU - Rosenson RS AD - Mount Sinai Icahn School of Medicine, New York, NY, USA. FAU - Stroes, E S AU - Stroes ES AD - Academic Medical Center, the Netherlands, Amsterdam, The Netherlands. LA - eng PT - Journal Article DEP - 20151020 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 EIN - Value Health. 2016 Jan;19(1):120 EDAT- 2015/11/05 06:00 MHDA- 2015/11/05 06:01 CRDT- 2015/11/05 06:00 PHST- 2015/11/05 06:00 [entrez] PHST- 2015/11/05 06:00 [pubmed] PHST- 2015/11/05 06:01 [medline] AID - S1098-3015(15)02999-X [pii] AID - 10.1016/j.jval.2015.09.923 [doi] PST - ppublish SO - Value Health. 2015 Nov;18(7):A401. doi: 10.1016/j.jval.2015.09.923. Epub 2015 Oct 20. PMID- 26532262 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160204 LR - 20160519 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 18 IP - 7 DP - 2015 Nov TI - Managing Patients With Statin-Associated Symptoms: Does Real-World Clinical Practice Align With Clinical Guidelines And Hta Recommendations In Europe? PG - A401 LID - 10.1016/j.jval.2015.09.924 [doi] LID - S1098-3015(15)03000-4 [pii] FAU - Hovingh, G K AU - Hovingh GK AD - Academic Medical Center, Amsterdam, The Netherlands. FAU - Gandra, S R AU - Gandra SR AD - Amgen, Inc., Thousand Oaks, CA, USA. FAU - McKendrick, J AU - McKendrick J AD - PRMA Consulting, Hampshire, UK. FAU - Dent, R AU - Dent R AD - Amgen, Inc., Thousand Oaks, CA, USA. FAU - Wieffer, H M AU - Wieffer HM AD - PRMA Consulting, Fleet, UK. FAU - Catapano, A L AU - Catapano AL AD - University of Milan, Milan, Italy. FAU - Oh, P AU - Oh P AD - Toronto Rehabilitation Institute, Toronto, ON, Canada. FAU - Rosenson, R S AU - Rosenson RS AD - Mount Sinai Icahn School of Medicine, New York, NY, USA. FAU - Stroes, E S AU - Stroes ES AD - Academic Medical Center, the Netherlands, Amsterdam, The Netherlands. LA - eng PT - Journal Article DEP - 20151020 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 EIN - Value Health. 2016 Jan;19(1):121 EDAT- 2015/11/05 06:00 MHDA- 2015/11/05 06:01 CRDT- 2015/11/05 06:00 PHST- 2015/11/05 06:00 [entrez] PHST- 2015/11/05 06:00 [pubmed] PHST- 2015/11/05 06:01 [medline] AID - S1098-3015(15)03000-4 [pii] AID - 10.1016/j.jval.2015.09.924 [doi] PST - ppublish SO - Value Health. 2015 Nov;18(7):A401. doi: 10.1016/j.jval.2015.09.924. Epub 2015 Oct 20. PMID- 26276885 OWN - NLM STAT- MEDLINE DCOM- 20160808 LR - 20170922 IS - 1942-3268 (Electronic) IS - 1942-3268 (Linking) VI - 8 IP - 5 DP - 2015 Oct TI - Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant. PG - 696-706 LID - 10.1161/CIRCGENETICS.115.001062 [doi] AB - BACKGROUND: Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT-Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant. METHODS AND RESULTS: In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: beta=-0.0047, P=1.63 x 10(-4); men: beta=-0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage disequilibrium (r(2) >/= 0.8) with rs4888378 were identified from 1000 Genome Project. ENCODE regulatory chromatin marks were used to create a shortlist of 6 possible regulatory variants. Electrophoretic mobility shift assays on the shortlist detected allele-specific protein binding to the lead SNP rs4888378; multiplexed competitor electrophoretic mobility shift assays implicated FOXA as the protein. Luciferase reporter assays on rs4888378 showed a significant 35% to 92% (P=0.0057; P=4.0 x 10(-22)) decrease in gene expression with the A allele. Expression quantitative trait loci analysis confirmed previously reported associations of rs4888378 with BCAR1 in vascular tissues. CONCLUSIONS: Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1-TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women, raising questions about the mechanism of the causal SNP on atherosclerosis. CI - (c) 2015 American Heart Association, Inc. FAU - Boardman-Pretty, Freya AU - Boardman-Pretty F AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.) f.boardman-pretty.10@ucl.ac.uk. FAU - Smith, Andrew J P AU - Smith AJ AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Cooper, Jackie AU - Cooper J AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Palmen, Jutta AU - Palmen J AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Folkersen, Lasse AU - Folkersen L AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Hamsten, Anders AU - Hamsten A AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Catapano, Alberico L AU - Catapano AL AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Melander, Olle AU - Melander O AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Price, Jacqueline F AU - Price JF AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Kumari, Meena AU - Kumari M AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Deanfield, John E AU - Deanfield JE AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Kivimaki, Mika AU - Kivimaki M AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Gertow, Karl AU - Gertow K AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Baragetti, Andrea AU - Baragetti A AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Norata, Giuseppe Danilo AU - Norata GD AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). FAU - Humphries, Steve E AU - Humphries SE AD - From the Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences (F.B.-P., A.J.P.S., J.C., J.P., S.E.H.), National Centre for Cardiovascular Prevention and Outcomes Institute of Cardiovascular Science (J.E.D.), Department of Epidemiology and Public Health (M. Kumari, M. Kivimaki), University College London, London, United Kingdom; Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark (L.F.); Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden (L.F., A.H., K.G.); Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, University of Milan, Milan, Italy (A.L.C., A.B., G.D.N.); IRCCS Multimedica, Milan, Italy (A.L.C.); Department of Clinical Sciences, Lund University, Malmo, Sweden (O.M.); The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, United Kingdom (J.F.P.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M. Kumari); and SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy (G.D.N., A.B.). LA - eng GR - RG/08/008/25291/British Heart Foundation/United Kingdom GR - GGP13002/Telethon/Italy GR - CZB/4/672/Chief Scientist Office/United Kingdom GR - RG/07/008/23674/RG/CSR NIH HHS/United States GR - RG/07/008/23674/British Heart Foundation/United Kingdom GR - RG2008/014/British Heart Foundation/United Kingdom GR - FS/13/6/29977/British Heart Foundation/United Kingdom GR - MR/K013351/1/Medical Research Council/United Kingdom GR - HS06516/HS/AHRQ HHS/United States GR - RG/98002/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20150814 PL - United States TA - Circ Cardiovasc Genet JT - Circulation. Cardiovascular genetics JID - 101489144 RN - 0 (BCAR1 protein, human) RN - 0 (Crk-Associated Substrate Protein) RN - 0 (DNA-Binding Proteins) RN - 9007-49-2 (DNA) SB - IM MH - Aged MH - Atherosclerosis/*genetics MH - *Carotid Intima-Media Thickness MH - Cell Line, Tumor MH - Chromosomes, Human, Pair 16 MH - Cohort Studies MH - Computational Biology MH - Coronary Artery Disease/*genetics MH - Crk-Associated Substrate Protein/*genetics MH - DNA/metabolism MH - DNA-Binding Proteins/metabolism MH - Disease Progression MH - Female MH - Gene Expression MH - Genes, Reporter MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide MH - Prospective Studies MH - Quantitative Trait Loci MH - Risk Factors MH - Sex Factors OTO - NOTNLM OT - atherosclerosis OT - carotid intima-media thickness OT - coronary artery disease OT - genetics OT - polymorphism, single nucleotide EDAT- 2015/08/16 06:00 MHDA- 2016/08/09 06:00 CRDT- 2015/08/16 06:00 PHST- 2015/02/13 00:00 [received] PHST- 2015/07/24 00:00 [accepted] PHST- 2015/08/16 06:00 [entrez] PHST- 2015/08/16 06:00 [pubmed] PHST- 2016/08/09 06:00 [medline] AID - CIRCGENETICS.115.001062 [pii] AID - 10.1161/CIRCGENETICS.115.001062 [doi] PST - ppublish SO - Circ Cardiovasc Genet. 2015 Oct;8(5):696-706. doi: 10.1161/CIRCGENETICS.115.001062. Epub 2015 Aug 14. PMID- 26180107 OWN - NLM STAT- MEDLINE DCOM- 20160503 LR - 20181202 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 38 IP - 10 DP - 2015 Oct TI - Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration. PG - 1921-9 LID - 10.2337/dc14-2732 [doi] AB - OBJECTIVE: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). CONCLUSIONS: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes. CI - (c) 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. FAU - Lorenz, Matthias W AU - Lorenz MW AD - Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany matthias.lorenz@em.uni-frankfurt.de. FAU - Price, Jackie F AU - Price JF AD - Centre for Population Health Sciences, University of Edinburgh, Edinburgh, U.K. FAU - Robertson, Christine AU - Robertson C AD - Centre for Population Health Sciences, University of Edinburgh, Edinburgh, U.K. FAU - Bots, Michiel L AU - Bots ML AD - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. FAU - Polak, Joseph F AU - Polak JF AD - Tufts University School of Medicine, Tufts Medical Center, Boston, MA. FAU - Poppert, Holger AU - Poppert H AD - Department of Neurology, University Hospital of the Technical University of Munich, Munich, Germany. FAU - Kavousi, Maryam AU - Kavousi M AD - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Dorr, Marcus AU - Dorr M AD - Department of Internal Medicine B/Cardiology, Greifswald University Clinic, Greifswald, Germany. FAU - Stensland, Eva AU - Stensland E AD - Department of Clinical Medicine, University of Tromso, Tromso, Norway. FAU - Ducimetiere, Pierre AU - Ducimetiere P AD - University of Paris Sud-XI, Paris, France. FAU - Ronkainen, Kimmo AU - Ronkainen K AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. FAU - Sitzer, Matthias AU - Sitzer M AD - Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany Department of Neurology, Klinikum Herford, Herford, Germany. FAU - Rundek, Tatjana AU - Rundek T AD - Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL. FAU - Lind, Lars AU - Lind L AD - Department of Medicine, Uppsala University, Uppsala, Sweden. FAU - Liu, Jing AU - Liu J AD - Department of Epidemiology, Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. FAU - Bergstrom, Goran AU - Bergstrom G AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Gothenburg, Sweden. FAU - Grigore, Liliana AU - Grigore L AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy IRCCS MultiMedica, Milan, Italy. FAU - Bokemark, Lena AU - Bokemark L AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Gothenburg, Sweden. FAU - Friera, Alfonsa AU - Friera A AD - Radiology Department, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Yanez, David AU - Yanez D AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Bickel, Horst AU - Bickel H AD - Department of Psychiatry, University Hospital of the Technical University of Munich, Munich, Germany. FAU - Ikram, M Arfan AU - Ikram MA AD - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Volzke, Henry AU - Volzke H AD - Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University of Greifswald, Greifswald, Germany German Centre for Cardiovascular Research, Greifswald, Germany. FAU - Johnsen, Stein Harald AU - Johnsen SH AD - Department of Clinical Medicine, University of Tromso, Tromso, Norway Department of Neurology and Neurophysiology, University Hospital of Northern Norway, Tromso, Norway. FAU - Empana, Jean Philippe AU - Empana JP AD - INSERM U 970, Paris, France. FAU - Tuomainen, Tomi-Pekka AU - Tuomainen TP AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Willeit, Peter AU - Willeit P AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K. FAU - Steinmetz, Helmuth AU - Steinmetz H AD - Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Desvarieux, Moise AU - Desvarieux M AD - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY Ecole des Hautes Etudes en Sante Publique, Paris, France INSERM U 738, Paris, France. FAU - Xie, Wuxiang AU - Xie W AD - Department of Epidemiology, Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. FAU - Schmidt, Caroline AU - Schmidt C AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Gothenburg, Sweden. FAU - Norata, Giuseppe D AU - Norata GD AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Suarez, Carmen AU - Suarez C AD - Internal Medicine Department, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Sander, Dirk AU - Sander D AD - Department of Neurology, University Hospital of the Technical University of Munich, Munich, Germany Department of Neurology, Benedictus Hospital Tutzing and Feldafing, Feldafing, Germany. FAU - Hofman, Albert AU - Hofman A AD - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands Department of Epidemiology, Harvard School of Public Health, Boston, MA. FAU - Schminke, Ulf AU - Schminke U AD - Department of Neurology, Greifswald University Clinic, Greifswald, Germany. FAU - Mathiesen, Ellisiv AU - Mathiesen E AD - Department of Clinical Medicine, University of Tromso, Tromso, Norway Department of Neurology and Neurophysiology, University Hospital of Northern Norway, Tromso, Norway. FAU - Plichart, Matthieu AU - Plichart M AD - INSERM U 970, Paris, France Gerontology Department, Broca Hospital, Paris, France. FAU - Kauhanen, Jussi AU - Kauhanen J AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Willeit, Johann AU - Willeit J AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. FAU - Sacco, Ralph L AU - Sacco RL AD - Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL. FAU - McLachlan, Stela AU - McLachlan S AD - Centre for Population Health Sciences, University of Edinburgh, Edinburgh, U.K. FAU - Zhao, Dong AU - Zhao D AD - Department of Epidemiology, Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. FAU - Fagerberg, Bjorn AU - Fagerberg B AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Gothenburg, Sweden. FAU - Catapano, Alberico L AU - Catapano AL AD - IRCCS MultiMedica, Milan, Italy Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Gabriel, Rafael AU - Gabriel R AD - Instituto de Investigacion IdiPAZ, Hospital Universitario La Paz, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Franco, Oscar H AU - Franco OH AD - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Bulbul, Alpaslan AU - Bulbul A AD - Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Scheckenbach, Frank AU - Scheckenbach F AD - Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Pflug, Anja AU - Pflug A AD - Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. FAU - Gao, Lu AU - Gao L AD - MRC Biostatistics Unit, Institute of Public Health, Cambridge, U.K. FAU - Thompson, Simon G AU - Thompson SG AD - Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K. LA - eng GR - U01 HL080295/HL/NHLBI NIH HHS/United States GR - R01 DE013094/DE/NIDCR NIH HHS/United States GR - N01 HC015103/HC/NHLBI NIH HHS/United States GR - RG/08/014/24067/British Heart Foundation/United Kingdom GR - U01-HL-080295/HL/NHLBI NIH HHS/United States GR - R01-DE-13094/DE/NIDCR NIH HHS/United States GR - N01HC55222/HL/NHLBI NIH HHS/United States GR - MR/L003120/1/Medical Research Council/United Kingdom GR - N01-HC-85086/HC/NHLBI NIH HHS/United States GR - N01-HC-15103/HC/NHLBI NIH HHS/United States GR - N01HC85086/HL/NHLBI NIH HHS/United States GR - R37 NS029993/NS/NINDS NIH HHS/United States GR - N01-HC-55222/HC/NHLBI NIH HHS/United States GR - N01HC85079/HL/NHLBI NIH HHS/United States GR - N01 HC035129/HC/NHLBI NIH HHS/United States GR - R37-NS-029993/NS/NINDS NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150715 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Atherosclerosis/diagnostic imaging MH - Carotid Artery, Common/diagnostic imaging MH - Carotid Intima-Media Thickness MH - Cooperative Behavior MH - Diabetes Mellitus, Type 2/*diagnostic imaging MH - Diabetic Angiopathies/*diagnostic imaging MH - Disease Progression MH - Female MH - Humans MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Risk Factors PMC - PMC4580609 EDAT- 2015/07/17 06:00 MHDA- 2016/05/04 06:00 CRDT- 2015/07/17 06:00 PHST- 2014/11/18 00:00 [received] PHST- 2015/06/20 00:00 [accepted] PHST- 2015/07/17 06:00 [entrez] PHST- 2015/07/17 06:00 [pubmed] PHST- 2016/05/04 06:00 [medline] AID - dc14-2732 [pii] AID - 10.2337/dc14-2732 [doi] PST - ppublish SO - Diabetes Care. 2015 Oct;38(10):1921-9. doi: 10.2337/dc14-2732. Epub 2015 Jul 15. PMID- 26435212 OWN - NLM STAT- MEDLINE DCOM- 20160413 LR - 20180225 IS - 1873-3735 (Electronic) IS - 0165-6147 (Linking) VI - 36 IP - 10 DP - 2015 Oct TI - Apolipoprotein C-III: From Pathophysiology to Pharmacology. PG - 675-687 LID - S0165-6147(15)00140-6 [pii] LID - 10.1016/j.tips.2015.07.001 [doi] AB - Apolipoprotein C-III (apoC-III) has a critical role in the metabolism of triglyceride (TG)-rich lipoproteins (TRLs). Animal models lacking the APOC3 gene exhibit reduced plasma TG levels, whereas the overexpression of APOC3 leads to increased TG levels. In humans, loss-of-function mutations in APOC3 are associated with reduced plasma TG levels and reduced risk for ischemic vascular disease and coronary heart disease. Several hypolipidemic agents have been shown to reduce apoC-III, including fibrates and statins, and antisense technology aimed at inhibiting APOC3 mRNA to decrease the production of apoC-III is currently in Phase III of clinical development. Here, we review the pathophysiological role of apoC-III in TG metabolism and the evidence supporting this apolipoprotein as an emerging target for hypertriglyceridemia (HTG) and associated cardiovascular disorders. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy. Electronic address: danilo.norata@unimi.it. FAU - Tsimikas, Sotirios AU - Tsimikas S AD - Department of Medicine, Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA, USA. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy; IRCCS Multimedica, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS Multimedica, Milan, Italy. LA - eng GR - GGP13002/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Trends Pharmacol Sci JT - Trends in pharmacological sciences JID - 7906158 RN - 0 (Apolipoprotein C-III) SB - IM MH - Animals MH - Apolipoprotein C-III/genetics/*metabolism MH - Coronary Disease/*genetics/metabolism/therapy MH - *Genetic Therapy MH - Humans MH - Lipid Metabolism OTO - NOTNLM OT - Triglycerides OT - coronary heart disease OT - lipoprotein lipase OT - remnant lipoproteins EDAT- 2015/10/06 06:00 MHDA- 2016/04/14 06:00 CRDT- 2015/10/06 06:00 PHST- 2015/05/19 00:00 [received] PHST- 2015/07/07 00:00 [revised] PHST- 2015/07/10 00:00 [accepted] PHST- 2015/10/06 06:00 [entrez] PHST- 2015/10/06 06:00 [pubmed] PHST- 2016/04/14 06:00 [medline] AID - S0165-6147(15)00140-6 [pii] AID - 10.1016/j.tips.2015.07.001 [doi] PST - ppublish SO - Trends Pharmacol Sci. 2015 Oct;36(10):675-687. doi: 10.1016/j.tips.2015.07.001. PMID- 26009596 OWN - NLM STAT- MEDLINE DCOM- 20160627 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 36 IP - 36 DP - 2015 Sep 21 TI - Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. PG - 2425-37 LID - 10.1093/eurheartj/ehv157 [doi] AB - Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C >/=5 mmol/L (190 mg/dL), or an LDL-C >/=4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is >/=3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if >10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Wiegman, Albert AU - Wiegman A AD - Department of Paediatrics, Academic Medical Center, University of Amsterdam, The Netherlands a.wiegman@amc.uva.nl. FAU - Gidding, Samuel S AU - Gidding SS AD - Nemours Cardiac Center, A. I. DuPont Hospital for Children, Wilmington, DE, USA. FAU - Watts, Gerald F AU - Watts GF AD - School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Western Australia, Australia. FAU - Chapman, M John AU - Chapman MJ AD - Pierre and Marie Curie University, Paris, France National Institute for Health and Medical Research (INSERM), Pitie-Salpetriere University Hospital, Paris, France. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Columbia University College of Physicians and Surgeons, New York, NY, USA Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, USA. FAU - Cuchel, Marina AU - Cuchel M AD - Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. FAU - Ose, Leiv AU - Ose L AD - Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Lipid Clinic, Oslo University Hospital, Oslo, Norway. FAU - Averna, Maurizio AU - Averna M AD - Department of Internal Medicine, University of Palermo, Italy. FAU - Boileau, Catherine AU - Boileau C AD - Diderot Medical School, University Paris 7, Paris, France Genetics Department, Bichat University Hospital, Paris, France INSERM U698, Paris, France. FAU - Boren, Jan AU - Boren J AD - Department of Medicine, Sahlgrenska Academy, Goteborg University, Gothenburg, Sweden Wallenberg Laboratory for Cardiovascular Research, Gothenburg, Sweden. FAU - Bruckert, Eric AU - Bruckert E AD - Department of Endocrinology and Prevention of Cardiovascular Disease, University Hospital Pitie-Salpetriere, Paris, France. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacology, Faculty of Pharmacy, University of Milano, Milan, Italy Multimedica IRCSS, Milan, Italy. FAU - Defesche, Joep C AU - Defesche JC AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. FAU - Descamps, Olivier S AU - Descamps OS AD - Centre Hospitalier Jolimont-Lobbes, Nivelles-Tubize, Belgium. FAU - Hegele, Robert A AU - Hegele RA AD - Robarts Research Institute, University of Western Ontario, London, ON, Canada. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. FAU - Humphries, Steve E AU - Humphries SE AD - Centre for Cardiovascular Genetics, University College London, Institute of Cardiovascular Sciences, London, UK. FAU - Kovanen, Petri T AU - Kovanen PT AD - Wihuri Research Institute, Helsinki, Finland. FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA AD - Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Masana, Luis AU - Masana L AD - Vascular Medicine and Metabolic Unit, Department of Medicine and Surgery, University Rovira and Virgili, Reus-Tarragona, Spain. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Pajukanta, Paivi AU - Pajukanta P AD - Department of Human Genetics, Center for Metabolic Disease Prevention, University of California, Los Angeles, USA. FAU - Parhofer, Klaus G AU - Parhofer KG AD - Department of Endocrinology and Metabolism, University of Munich, Munich, Germany. FAU - Raal, Frederick J AU - Raal FJ AD - Carbohydrate & Lipid Metabolism Research Unit; and Division of Endocrinology & Metabolism, University of the Witwatersrand, Johannesburg, South Africa. FAU - Ray, Kausik K AU - Ray KK AD - Department of Primary Care and Public Health, School of Public Health, Imperial College, London, UK. FAU - Santos, Raul D AU - Santos RD AD - Lipid Clinic of the Heart Institute (InCor), University of Sao Paulo, Sao Paulo, Brazil Department of Cardiology, University of Sao Paulo Medical School, Sao Paulo, Brazil. FAU - Stalenhoef, Anton F H AU - Stalenhoef AF AD - Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. FAU - Steinhagen-Thiessen, Elisabeth AU - Steinhagen-Thiessen E AD - Evangelisches Geriatriezentrum Berlin gGmbH (EGZB), Berlin, Germany Charite - Universitatsmedizin, Berlin, Germany. FAU - Stroes, Erik S AU - Stroes ES AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. FAU - Taskinen, Marja-Riitta AU - Taskinen MR AD - Research Programs Unit, Diabetes & Obesity, University of Helsinki and Heart & Lung Centre, Helsinki University Hospital, Helsinki, Finland. FAU - Tybjaerg-Hansen, Anne AU - Tybjaerg-Hansen A AD - Department of Clinical Biochemistry, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Wiklund, Olov AU - Wiklund O AD - Department of Experimental and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. CN - European Atherosclerosis Society Consensus Panel LA - eng GR - P01 HL028481/HL/NHLBI NIH HHS/United States GR - R01 HL095056/HL/NHLBI NIH HHS/United States GR - RG/08/008/25291/British Heart Foundation/United Kingdom PT - Journal Article PT - Review DEP - 20150525 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 SB - IM MH - Adolescent MH - Adult MH - Atherosclerosis/diagnosis/drug therapy MH - Carotid Intima-Media Thickness MH - Child MH - Clinical Laboratory Techniques/methods MH - Cost of Illness MH - Counseling MH - Diet MH - Dietary Supplements MH - Early Diagnosis MH - Economics, Medical MH - Evidence-Based Medicine MH - Female MH - Genetic Testing MH - Heterozygote MH - Homozygote MH - Humans MH - Hyperlipoproteinemia Type II/diagnosis/*drug therapy/genetics MH - Life Expectancy MH - Medication Adherence MH - Middle Aged MH - Pregnancy MH - Pregnancy Complications/etiology MH - Risk Factors MH - Young Adult PMC - PMC4576143 OTO - NOTNLM OT - Adolescents OT - Children OT - Consensus statement OT - Diagnosis OT - Ezetimibe OT - Familial hypercholesterolaemia OT - LDL cholesterol OT - PCSK9 inhibitor OT - Statin OT - Treatment IR - Averna M FIR - Averna, Maurizio IR - Boileau C FIR - Boileau, Catherine IR - Boren J FIR - Boren, Jan IR - Bruckert E FIR - Bruckert, Eric IR - Catapano AL FIR - Catapano, Alberico L IR - Chapman MJ FIR - Chapman, M John IR - Cuchel M FIR - Cuchel, Marina IR - Defesche JC FIR - Defesche, Joep C IR - Descamps OS FIR - Descamps, Olivier S IR - Gidding SS FIR - Gidding, Samuel S IR - Ginsberg HN FIR - Ginsberg, Henry N IR - Hegele RA FIR - Hegele, Robert A IR - Hovingh GK FIR - Hovingh, G Kees IR - Humphries SE FIR - Humphries, Steve E IR - Kovanen PT FIR - Kovanen, Petri T IR - Kuivenhoven JA FIR - Kuivenhoven, Jan Albert IR - Masana L FIR - Masana, Luis IR - Nordestgaard BG FIR - Nordestgaard, Borge G IR - Ose L FIR - Ose, Leiv IR - Pajukanta P FIR - Pajukanta, Paivi IR - Parhofer KG FIR - Parhofer, Klaus G IR - Raal FJ FIR - Raal, Frederick J IR - Ray KK FIR - Ray, Kausik K IR - Santos RD FIR - Santos, Raul D IR - Stalenhoef AF FIR - Stalenhoef, Anton F H IR - Steinhagen-Thiessen E FIR - Steinhagen-Thiessen, Elisabeth IR - Stroes ES FIR - Stroes, Erik S IR - Taskinen MR FIR - Taskinen, Marja-Riitta IR - Tybjaerg-Hansen A FIR - Tybjaerg-Hansen, Anne IR - Watts GF FIR - Watts, Gerald F IR - Wiegman A FIR - Wiegman, Albert IR - Wiklund O FIR - Wiklund, Olov IR - Gidding SS FIR - Gidding, Samuel S IR - Watts GF FIR - Watts, Gerald F IR - Chapman MJ FIR - Chapman, M John IR - Ginsberg HN FIR - Ginsberg, Henry N IR - Cuchel M FIR - Cuchel, Marina IR - Ose L FIR - Ose, Leiv IR - Chapman MJ FIR - Chapman, M John IR - Ginsberg HN FIR - Ginsberg, Henry N EDAT- 2015/05/27 06:00 MHDA- 2016/06/28 06:00 CRDT- 2015/05/27 06:00 PHST- 2015/02/16 00:00 [received] PHST- 2015/04/19 00:00 [accepted] PHST- 2015/05/27 06:00 [entrez] PHST- 2015/05/27 06:00 [pubmed] PHST- 2016/06/28 06:00 [medline] AID - ehv157 [pii] AID - 10.1093/eurheartj/ehv157 [doi] PST - ppublish SO - Eur Heart J. 2015 Sep 21;36(36):2425-37. doi: 10.1093/eurheartj/ehv157. Epub 2015 May 25. PMID- 26315511 OWN - NLM STAT- MEDLINE DCOM- 20160504 LR - 20150828 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 19 DP - 2015 Sep TI - A review of the evidence on reducing macrovascular risk in patients with atherogenic dyslipidaemia: A report from an expert consensus meeting on the role of fenofibrate-statin combination therapy. PG - 1-12 LID - 10.1016/S1567-5688(15)30001-5 [doi] LID - S1567-5688(15)30001-5 [pii] AB - A meeting of European experts in cardiovascular (CV) disease and lipids was convened in Paris, France, on 10 November 2014 to discuss lipid profile, and in particular atherogenic dyslipidaemia (AD), and associated CV risk. Key points that were raised and discussed during the meeting are summarised in this paper, which also accounts for further discussion and agreement on these points by the group of experts. Elevated levels of low-density lipoprotein cholesterol (LDL-c) are commonly associated with a greater CV risk than low LDL-c levels, and are routinely managed with statins. However, even for patients controlled on statins and achieving low LDL-c levels, abnormal lipid profiles observed in some patients (i.e. elevated triglyceride levels, with/without low levels of high-density lipoprotein cholesterol [HDL-c]) have been linked to the presence of a residual CV risk. Therefore, it is recommended that both triglyceride and HDL-c levels be measured, to allow for the overall CV residual risk to be adequately managed. Favourable safety and clinical data support the combination of statins with other lipid-lowering agents, such as fenofibrate. Patients who have elevated triglyceride levels plus low levels of HDL-c are most likely to achieve clinical benefit from fenofibrate-statin combination therapy. In these patients with AD, achieving target non-HDL-c levels should be a key focus of CV risk management, and the use of non-HDL-c was advocated to provide a better measure of CV risk than LDL-c levels. CI - (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Aguiar, Carlos AU - Aguiar C AD - Hospital Santa Cruz, Centro Hospitalar de Lisboa Ocidental, EPE, Carnaxide, Portugal. FAU - Alegria, Eduardo AU - Alegria E AD - Cardiology Department, Policlinica Gipuzkoa, San Sebastian, Spain. FAU - Bonadonna, Riccardo C AU - Bonadonna RC AD - Division of Endocrinology, Department of Clinical and Experimental Medicine, University of Parma and Azienda Ospedaliera Universitaria of Parma, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Cosentino, Francesco AU - Cosentino F AD - Cardiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Elisaf, Moses AU - Elisaf M AD - Department of Internal Medicine, University of Ioannina Medical School, Greece. FAU - Farnier, Michel AU - Farnier M AD - Point Medical, Dijon, France. FAU - Ferrieres, Jean AU - Ferrieres J AD - Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France. FAU - Filardi, Pasquale Perrone AU - Filardi PP AD - Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. FAU - Hancu, Nicolae AU - Hancu N AD - Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. FAU - Kayikcioglu, Meral AU - Kayikcioglu M AD - Department of Cardiology, Ege University Medical School, Izmir, Turkey. FAU - Mello E Silva, Alberto AU - Mello E Silva A AD - Hospital Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal. FAU - Millan, Jesus AU - Millan J AD - Hospital General Universitario Gregorio Maranon, Facultad de Medicina de la Universidad Complutense, Madrid, Spain. FAU - Reiner, Zeljko AU - Reiner Z AD - University Hospital Center, School of Medicine, University of Zagreb, Croatia. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Hacettepe University, Ankara, Turkey. FAU - Valensi, Paul AU - Valensi P AD - Department of Endocrinology Diabetology Nutrition, Jean Verdier Hospital, APHP, Paris Nord University, CRNH-IdF, CINFO, Bondy, France. FAU - Viigimaa, Margus AU - Viigimaa M AD - North Estonia Medical Centre, Tallinn University of Technology, Estonia. FAU - Vrablik, Michal AU - Vrablik M AD - 3rd Department of Internal Medicine, 1st Medical Faculty, Charles University, Prague, Czech Republic. FAU - Zambon, Alberto AU - Zambon A AD - Clinica Medica, Department of Medicine, University of Padova, Italy. FAU - Zamorano, Jose Luis AU - Zamorano JL AD - University Alcala de Henares, Hospital Ramon y Cajal, Madrid, Spain. FAU - Ferrari, Roberto AU - Ferrari R AD - Department of Cardiology and LTTA Centre, University Hospital of Ferrara and Maria Cecilia Hospital, GVM Care & Research, E.S: Health Science Foundation, Cotignola, Italy. LA - eng PT - Consensus Development Conference PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipids) RN - U202363UOS (Fenofibrate) SB - IM MH - Atherosclerosis/*drug therapy MH - Cardiovascular Diseases/*prevention & control MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Drug Therapy, Combination MH - Dyslipidemias/*drug therapy MH - Europe MH - Fenofibrate/*therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypolipidemic Agents/*therapeutic use MH - Lipids/blood MH - Paris OTO - NOTNLM OT - Atherogenic dyslipidaemia OT - cardiovascular risk OT - cholesterol OT - combination therapy OT - fenofibrate OT - statins OT - triglycerides EDAT- 2015/09/01 06:00 MHDA- 2016/05/05 06:00 CRDT- 2015/08/29 06:00 PHST- 2015/08/29 06:00 [entrez] PHST- 2015/09/01 06:00 [pubmed] PHST- 2016/05/05 06:00 [medline] AID - S1567-5688(15)30001-5 [pii] AID - 10.1016/S1567-5688(15)30001-5 [doi] PST - ppublish SO - Atheroscler Suppl. 2015 Sep;19:1-12. doi: 10.1016/S1567-5688(15)30001-5. PMID- 26091974 OWN - NLM STAT- MEDLINE DCOM- 20160428 LR - 20150721 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 241 IP - 2 DP - 2015 Aug TI - IMPROVE-IT and genetics reaffirm the causal role of LDL in Cardiovascular Disease. PG - 498-501 LID - 10.1016/j.atherosclerosis.2015.06.008 [doi] LID - S0021-9150(15)01362-3 [pii] FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences University of Milan and IRCCS Multimedica, Via Balzaretti 9, 20133 Milano, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Ference, Brian A AU - Ference BA AD - Division of Cardiovascular Medicine Wayne State University School of Medicine UHC, 2E2 Detroit, MI 48202, USA. LA - eng PT - Journal Article DEP - 20150610 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Membrane Proteins) RN - 0 (NPC1L1 protein, human) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Cardiovascular Diseases/*blood/etiology/*genetics MH - Cholesterol, LDL/*blood MH - Drug Approval MH - Ezetimibe/administration & dosage MH - Genetic Predisposition to Disease MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage MH - Membrane Proteins/genetics MH - Mendelian Randomization Analysis MH - Randomized Controlled Trials as Topic MH - Research Design EDAT- 2015/06/21 06:00 MHDA- 2016/04/29 06:00 CRDT- 2015/06/21 06:00 PHST- 2015/06/04 00:00 [accepted] PHST- 2015/06/21 06:00 [entrez] PHST- 2015/06/21 06:00 [pubmed] PHST- 2016/04/29 06:00 [medline] AID - S0021-9150(15)01362-3 [pii] AID - 10.1016/j.atherosclerosis.2015.06.008 [doi] PST - ppublish SO - Atherosclerosis. 2015 Aug;241(2):498-501. doi: 10.1016/j.atherosclerosis.2015.06.008. Epub 2015 Jun 10. PMID- 25881051 OWN - NLM STAT- MEDLINE DCOM- 20160407 LR - 20170922 IS - 2567-689X (Electronic) IS - 0340-6245 (Linking) VI - 114 IP - 1 DP - 2015 Jul TI - Fibronectin extra domain A stabilises atherosclerotic plaques in apolipoprotein E and in LDL-receptor-deficient mice. PG - 186-97 LID - 10.1160/TH14-09-0790 [doi] AB - The primary transcript of fibronectin undergoes alternative splicing in the cassette-type EDA and EDB exons and in the IIICs segment to generate different protein isoforms. Human carotid atherosclerotic plaques with a more stable phenotype are enriched with EDA containing fibronectin (FN-EDA). The aim of this study was to investigate the role of EDA containing fibronectin during atherogenesis. Mice constitutively expressing or lacking the EDA domain of fibronectin (EDA+/+ or EDA-/-)were crossed with ApoE-/- or LDL-R-/- mice and fed with a western type diet for 12 weeks. Lack of FN-EDA resulted in reduced atherosclerosis and in a plaque phenotype characterised by decreased calponin positive VSMC's (-15 %) and increased macrophages (+20 %). This was paralleled by increased MMP2, MMP9, and reduced TIMP2, collagen 1A1, 1A2 and 3A1 gene expression compared to that of wild-type and EDA+/+ mice. In vitro, VSMCs and macrophages isolated from EDA-/- miceshowed increased MMPs expression and activity compared to wild-type or EDA+/+ mice. Albumin-Cre recombinase/EDA+/+/ApoE-/- mice, which produceEDA containing FN only in peripheral tissues, presented an extension, a composition and a gene expression pattern in the atherosclerotic lesions similar to that of controls. The inclusion of EDA in FN results in larger atherosclerotic plaques compared to mice lacking EDA but with a more favourable phenotype in two animals models of atherosclerosis. This effect depends on the EDA-containing fibronectin produced by cells in the vasculature but not in the liver. These observations set the stage for investigating the properties of circulating EDA containing FN in improving plaque stability. FAU - Pulakazhi Venu, Vivek Krishna AU - Pulakazhi Venu VK FAU - Uboldi, Patrizia AU - Uboldi P FAU - Dhyani, Ashish AU - Dhyani A FAU - Patrini, Alessandro AU - Patrini A FAU - Baetta, Roberta AU - Baetta R FAU - Ferri, Nicola AU - Ferri N FAU - Corsini, Alberto AU - Corsini A FAU - Muro, Andres F AU - Muro AF FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Alberico Luigi Catapano, Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy, Tel.: +39 02 50318302, Fax: +39 02 50318386, E-mail: alberico.catapano@unimi.it. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Giuseppe Danilo Norata, Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy, Tel.: +39 02 50318313, Fax: +39 02 50318386, E-mail: danilo.norata@unimi.it. LA - eng GR - GGP13002/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150416 PL - Germany TA - Thromb Haemost JT - Thrombosis and haemostasis JID - 7608063 RN - 0 (Apolipoproteins E) RN - 0 (Biomarkers) RN - 0 (Calcium-Binding Proteins) RN - 0 (Fibronectins) RN - 0 (Microfilament Proteins) RN - 0 (Receptors, LDL) RN - 0 (calponin) RN - 0 (extra domain A fibronectin, mouse) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.24 (Mmp2 protein, mouse) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.35 (Mmp9 protein, mouse) SB - IM CIN - Thromb Haemost. 2015 Jul;114(1):4. PMID: 26062571 MH - Animals MH - Aorta/metabolism/pathology MH - Aortic Diseases/genetics/*metabolism/pathology/prevention & control MH - Apolipoproteins E/*deficiency/genetics MH - Atherosclerosis/genetics/*metabolism/pathology/prevention & control MH - Biomarkers/metabolism MH - Calcium-Binding Proteins/metabolism MH - Cells, Cultured MH - Collagen/metabolism MH - Diet, High-Fat MH - Disease Models, Animal MH - Fibronectins/deficiency/genetics/*metabolism MH - Genotype MH - Macrophages/metabolism MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Mice, Knockout MH - Microfilament Proteins/metabolism MH - Muscle, Smooth, Vascular/*metabolism/pathology MH - Myocytes, Smooth Muscle/*metabolism/pathology MH - Phenotype MH - *Plaque, Atherosclerotic MH - Receptors, LDL/*deficiency/genetics MH - Tissue Inhibitor of Metalloproteinase-2/metabolism OTO - NOTNLM OT - Atherosclerosis OT - extracellular matrix OT - lipoproteins EDAT- 2015/04/17 06:00 MHDA- 2016/04/08 06:00 CRDT- 2015/04/17 06:00 PHST- 2014/09/22 00:00 [received] PHST- 2015/02/05 00:00 [accepted] PHST- 2015/04/17 06:00 [entrez] PHST- 2015/04/17 06:00 [pubmed] PHST- 2016/04/08 06:00 [medline] AID - 14-09-0790 [pii] AID - 10.1160/TH14-09-0790 [doi] PST - ppublish SO - Thromb Haemost. 2015 Jul;114(1):186-97. doi: 10.1160/TH14-09-0790. Epub 2015 Apr 16. PMID- 25964372 OWN - NLM STAT- MEDLINE DCOM- 20150810 LR - 20181113 IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 212 IP - 6 DP - 2015 Jun 1 TI - An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. PG - 905-25 LID - 10.1084/jem.20141268 [doi] AB - Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. CI - (c) 2015 Doni et al. FAU - Doni, Andrea AU - Doni A AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Musso, Tiziana AU - Musso T AD - Department of Public Health and Microbiology, University of Turin, 10124 Turin, Italy. FAU - Morone, Diego AU - Morone D AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Bastone, Antonio AU - Bastone A AD - Department of Molecular Biochemistry and Pharmachology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy. FAU - Zambelli, Vanessa AU - Zambelli V AD - Department of Health Science, University of Milano-Bicocca, 20126 Monza, Italy. FAU - Sironi, Marina AU - Sironi M AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Castagnoli, Carlotta AU - Castagnoli C AD - Department of Plastic Surgery, Burn Unit and Skin Bank, Centro Traumatologico Ortopedico (CTO) Hospital, 10126 Turin, Italy. FAU - Cambieri, Irene AU - Cambieri I AD - Department of Plastic Surgery, Burn Unit and Skin Bank, Centro Traumatologico Ortopedico (CTO) Hospital, 10126 Turin, Italy. FAU - Stravalaci, Matteo AU - Stravalaci M AD - Department of Molecular Biochemistry and Pharmachology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy. FAU - Pasqualini, Fabio AU - Pasqualini F AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Laface, Ilaria AU - Laface I AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Valentino, Sonia AU - Valentino S AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Tartari, Silvia AU - Tartari S AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Ponzetta, Andrea AU - Ponzetta A AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Maina, Virginia AU - Maina V AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Barbieri, Silvia S AU - Barbieri SS AD - IRCCS - Centro Cardiologico Monzino, 20138 Milan, Italy. FAU - Tremoli, Elena AU - Tremoli E AD - IRCCS - Centro Cardiologico Monzino, 20138 Milan, Italy Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy IRCCS - Multimedica, 20099 Milan, Italy. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy Societa Italiana per lo Studio della Arteriosclerosi (SISA) Center for the Study of Atherosclerosis, Bassini Hospital, 20154 Milan, Italy. FAU - Bottazzi, Barbara AU - Bottazzi B AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Garlanda, Cecilia AU - Garlanda C AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy. FAU - Mantovani, Alberto AU - Mantovani A AD - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Humanitas Clinical and Research Center, 20089 Milan, Italy Humanitas University, 20089 Milan, Italy alberto.mantovani@humanitasresearch.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150511 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Nerve Tissue Proteins) RN - 0 (neuronal pentraxin) RN - 9001-31-4 (Fibrin) RN - 9001-91-6 (Plasminogen) RN - 9007-34-5 (Collagen) RN - 9007-41-4 (C-Reactive Protein) SB - IM CIN - J Exp Med. 2015 Jun 1;212(6):829. PMID: 26034115 MH - Animals MH - Arteries/pathology MH - Blood Coagulation MH - C-Reactive Protein/*metabolism MH - Cell-Free System MH - Collagen/metabolism MH - Female MH - Fibrin/metabolism MH - Fibrinolysis MH - Gene Expression Regulation MH - Hydrogen-Ion Concentration MH - Immunity, Humoral/*physiology MH - Immunity, Innate MH - Leukocytes/cytology MH - Liver/injuries MH - Lung Injury/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Confocal MH - Nerve Tissue Proteins/*metabolism MH - Phenotype MH - Plasminogen/metabolism MH - Protein Structure, Tertiary MH - Skin/immunology/pathology MH - Surface Plasmon Resonance MH - Thrombosis/pathology MH - Wound Healing PMC - PMC4451130 EDAT- 2015/05/13 06:00 MHDA- 2015/08/11 06:00 CRDT- 2015/05/13 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2015/04/22 00:00 [accepted] PHST- 2015/05/13 06:00 [entrez] PHST- 2015/05/13 06:00 [pubmed] PHST- 2015/08/11 06:00 [medline] AID - jem.20141268 [pii] AID - 10.1084/jem.20141268 [doi] PST - ppublish SO - J Exp Med. 2015 Jun 1;212(6):905-25. doi: 10.1084/jem.20141268. Epub 2015 May 11. PMID- 25894795 OWN - NLM STAT- MEDLINE DCOM- 20160111 LR - 20181113 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 17 IP - 5 DP - 2015 May TI - Statin intolerance: diagnosis and remedies. PG - 27 LID - 10.1007/s11886-015-0582-z [doi] AB - Despite the efficacy of statins in reducing cardiovascular events in both primary and secondary prevention, the adherence to statin therapy is not optimal, mainly due to the occurrence of muscular adverse effects. Several risk factors may concur to the development of statin-induced myotoxicity, including patient-related factors (age, sex, and race), statin properties (dose, lipophilicity, and type of metabolism), and the concomitant administration of other drugs. Thus, the management of patients intolerant to statins, particularly those at high or very high cardiovascular risk, involves alternative therapies, including the switch to another statin or the use of intermittent dosage statin regimens, as well as nonstatin lipid lowering drugs (ezetimibe and fibrates) or new hypolipidemic drugs such as PCSK9 monoclonal antibodies, the antisense oligonucleotide against the coding region of human apolipoprotein B mRNA (mipomersen), and microsomal triglyceride transfer protein inhibitor lomitapide. Ongoing clinical trials will reveal whether the lipid-lowering effects of alternative therapies to statins can also translate into a cardiovascular benefit. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Via M. Gorki 50, Cinisello Balsamo, Milan, Italy, angela.pirillo@guest.unimi.it. FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Anticholesteremic Agents) RN - 0 (Fibric Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Oligonucleotides) RN - 9GJ8S4GU0M (mipomersen) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Animals MH - Anticholesteremic Agents/*adverse effects MH - Cardiovascular Diseases/*prevention & control MH - Dietary Supplements MH - Ezetimibe/adverse effects MH - Fibric Acids/adverse effects MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Hypolipidemic Agents/*adverse effects MH - Myalgia/*chemically induced MH - Oligonucleotides/adverse effects MH - Randomized Controlled Trials as Topic MH - Risk Factors EDAT- 2015/04/22 06:00 MHDA- 2016/01/12 06:00 CRDT- 2015/04/21 06:00 PHST- 2015/04/21 06:00 [entrez] PHST- 2015/04/22 06:00 [pubmed] PHST- 2016/01/12 06:00 [medline] AID - 10.1007/s11886-015-0582-z [doi] PST - ppublish SO - Curr Cardiol Rep. 2015 May;17(5):27. doi: 10.1007/s11886-015-0582-z. PMID- 25748827 OWN - NLM STAT- MEDLINE DCOM- 20151223 LR - 20181202 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 108 IP - 2 DP - 2015 May TI - Incretin-based drugs and risk of acute pancreatitis: A nested-case control study within a healthcare database. PG - 243-9 LID - 10.1016/j.diabres.2015.02.013 [doi] LID - S0168-8227(15)00113-8 [pii] AB - To assess the association between use of incretin-based drugs for diabetes mellitus and the occurrence of acute pancreatitis. A population-based, nested case-control study was performed within a cohort of 166,591 patients from the Lombardy region (Italy) aged 40 years or older who were newly treated with oral antihyperglycaemic agents between 2004 and 2007. Cases were 666 patients who experienced acute pancreatitis from April 1, 2008 until December 31, 2012. For each case patient, up to 20 controls were randomly selected from the cohort and matched on gender, age at cohort entry, and date of index prescription. Conditional logistic regression was used to model the risk of acute pancreatitis associated with use of incretin-based drugs within 30 days before hospitalization, after adjustment for several risk factors, including the use of other antihyperglycaemic agents. Sensitivity analyses were performed in order to account for possible sources of systematic uncertainty. Use of incretin-based drugs within 30 days was reported by 17 (2.6%) cases of acute pancreatitis versus 193 (1.5%) controls. The corresponding multivariate odds ratio was 1.75 (95% confidence interval, 1.02 to 2.99). Slightly lower and no significant excess risks were observed by shortening (15 days) and increasing (60 and 90 days) the time-window at risk. This study supports a possible increased risk of acute pancreatitis in relation to use of incretin-based drugs reported in a few previous studies. However, given the potential for bias and the inconsistency with other studies, additional investigations are needed to clarify the safety of incretin-based-drugs. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Soranna, Davide AU - Soranna D AD - Dipartimento di Statistica e Metodi Quantitativi, Sezione di Biostatistica, Epidemiologia e Sanita Pubblica, Universita Milano-Bicocca, Milan, Italy. FAU - Bosetti, Cristina AU - Bosetti C AD - Dipartimento di Epidemiologia, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. FAU - Casula, Manuela AU - Casula M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita di Milano, Milan, Italy; IRCSS Multimedica, Milan, Italy. FAU - Vecchia, Carlo L A AU - Vecchia CL AD - Dipartimento di Scienze Cliniche e di Comunita, Universita Milano, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Unita Organizzativa Governo dei dati, delle strategie e piani del sistema sanitario, Regione Lombardia, Milan, Italy. FAU - Corrao, Giovanni AU - Corrao G AD - Dipartimento di Statistica e Metodi Quantitativi, Sezione di Biostatistica, Epidemiologia e Sanita Pubblica, Universita Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. LA - eng PT - Journal Article DEP - 20150223 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Adult MH - Aged MH - Case-Control Studies MH - Databases, Factual/statistics & numerical data MH - Diabetes Mellitus/*drug therapy MH - Female MH - Hospitalization/statistics & numerical data MH - Humans MH - Hypoglycemic Agents/*adverse effects/*therapeutic use MH - Incretins/*adverse effects/*therapeutic use MH - Italy/epidemiology MH - Logistic Models MH - Male MH - Middle Aged MH - Odds Ratio MH - Pancreatitis/*chemically induced/*epidemiology MH - Prevalence MH - Risk Factors OTO - NOTNLM OT - Acute pancreatitis OT - Antihyperglycaemic agents OT - Drug safety OT - Healthcare databases OT - Incretin-based drugs OT - Nested case-control study EDAT- 2015/03/10 06:00 MHDA- 2015/12/24 06:00 CRDT- 2015/03/10 06:00 PHST- 2014/09/29 00:00 [received] PHST- 2015/01/13 00:00 [revised] PHST- 2015/02/13 00:00 [accepted] PHST- 2015/03/10 06:00 [entrez] PHST- 2015/03/10 06:00 [pubmed] PHST- 2015/12/24 06:00 [medline] AID - S0168-8227(15)00113-8 [pii] AID - 10.1016/j.diabres.2015.02.013 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2015 May;108(2):243-9. doi: 10.1016/j.diabres.2015.02.013. Epub 2015 Feb 23. PMID- 25694464 OWN - NLM STAT- MEDLINE DCOM- 20160201 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 36 IP - 17 DP - 2015 May 1 TI - Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. PG - 1012-22 LID - 10.1093/eurheartj/ehv043 [doi] AB - Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Stroes, Erik S AU - Stroes ES AD - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands e.s.stroes@amc.uva.nl. FAU - Thompson, Paul D AU - Thompson PD AD - Hartford Hospital, Hartford, CT, USA. FAU - Corsini, Alberto AU - Corsini A AD - University of Milan and Multimedica IRCSS Milano, Italy. FAU - Vladutiu, Georgirene D AU - Vladutiu GD AD - School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. FAU - Raal, Frederick J AU - Raal FJ AD - University of the Witwatersrand, Johannesburg, South Africa. FAU - Ray, Kausik K AU - Ray KK AD - St. Georges's University of London, UK. FAU - Roden, Michael AU - Roden M AD - Department of Endocrinology and Diabetology, University Hospital Dusseldorf Heinrich-Heine University, and Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Germany. FAU - Stein, Evan AU - Stein E AD - Metabolic and Atherosclerosis Research Centre, Cincinnati, OH, USA. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Hacettepe University, Ankara, Turkey. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Denmark. FAU - Bruckert, Eric AU - Bruckert E AD - Pitie-Salpetriere University Hospital, Paris, France. FAU - De Backer, Guy AU - De Backer G AD - Ghent University, Ghent, Belgium. FAU - Krauss, Ronald M AU - Krauss RM AD - Children's Hospital Oakland Research Institute, Oakland, CA, USA. FAU - Laufs, Ulrich AU - Laufs U AD - Universitatsklinikum des Saarlandes, Homburg/Saar, Germany. FAU - Santos, Raul D AU - Santos RD AD - University of Sao Paulo, Brazil. FAU - Hegele, Robert A AU - Hegele RA AD - Western University, London, ON, Canada. FAU - Hovingh, G Kees AU - Hovingh GK AD - Academic Medical Center, University of Amsterdam, The Netherlands. FAU - Leiter, Lawrence A AU - Leiter LA AD - Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Canada. FAU - Mach, Francois AU - Mach F AD - Cardiology Service, HUG, Geneva, Switzerland. FAU - Marz, Winfried AU - Marz W AD - Synlab Center of Laboratory Diagnostics Heidelberg, Heidelberg, Germany. FAU - Newman, Connie B AU - Newman CB AD - New York University School of Medicine, New York, USA. FAU - Wiklund, Olov AU - Wiklund O AD - Sahlgrenska University Hospital, Gothenburg, Sweden. FAU - Jacobson, Terry A AU - Jacobson TA AD - Emory University School of Medicine, Atlanta, GA, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan and Multimedica IRCSS Milano, Italy. FAU - Chapman, M John AU - Chapman MJ AD - INSERM, Pitie-Salpetriere University Hospital, Paris, France. FAU - Ginsberg, Henry N AU - Ginsberg HN CN - European Atherosclerosis Society Consensus Panel LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150218 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (CETP protein, human) RN - 0 (Cholesterol Ester Transfer Proteins) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - EC 2.7.3.2 (Creatine Kinase) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Cholesterol Ester Transfer Proteins/antagonists & inhibitors MH - Complementary Therapies MH - Consensus MH - Creatine Kinase/metabolism MH - Diet MH - Genetic Predisposition to Disease/etiology MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/pharmacokinetics MH - Hypolipidemic Agents/therapeutic use MH - Mitochondria, Muscle MH - Mitochondrial Diseases/complications MH - Muscular Diseases/*chemically induced/diagnosis/therapy MH - Proprotein Convertase 9 MH - Proprotein Convertases/antagonists & inhibitors MH - Risk Factors MH - Serine Endopeptidases PMC - PMC4416140 OTO - NOTNLM OT - Cholesterol OT - Consensus statement OT - Lipids OT - Mitochondrial OT - Muscle symptoms OT - Myalgia OT - Myopathy OT - Statin OT - Statin intolerance IR - Stroes E FIR - Stroes, Erik IR - Thompson PD FIR - Thompson, Paul D IR - Corsini A FIR - Corsini, Alberto IR - Vladutiu GD FIR - Vladutiu, Georgirene D IR - Raal FJ FIR - Raal, Frederick J IR - Ray KK FIR - Ray, Kausik K IR - Roden M FIR - Roden, Michael IR - Stein E FIR - Stein, Evan IR - Tokgozoglu L FIR - Tokgozoglu, Lale IR - Nordestgaard BG FIR - Nordestgaard, Borge G IR - Bruckert E FIR - Bruckert, Eric IR - Krauss RM FIR - Krauss, Ronald M IR - Laufs U FIR - Laufs, Ulrich IR - Santos RD FIR - Santos, Raul D IR - Marz W FIR - Marz, Winfried IR - Newman CB FIR - Newman, Connie B IR - Chapman M FIR - Chapman, M John IR - Ginsberg HN FIR - Ginsberg, Henry N IR - Chapman M FIR - Chapman, M John IR - Ginsberg HN FIR - Ginsberg, Henry N IR - de Backer G FIR - de Backer, Guy IR - Catapano AL FIR - Catapano, Alberico L IR - Hegele RA FIR - Hegele, Robert A IR - Hovingh G FIR - Hovingh, G Kees IR - Jacobson TA FIR - Jacobson, Terry A IR - Leiter L FIR - Leiter, Lawrence IR - Mach F FIR - Mach, Francois IR - Wiklund O FIR - Wiklund, Olov EDAT- 2015/02/20 06:00 MHDA- 2016/02/02 06:00 CRDT- 2015/02/20 06:00 PHST- 2014/12/21 00:00 [received] PHST- 2015/01/26 00:00 [accepted] PHST- 2015/02/20 06:00 [entrez] PHST- 2015/02/20 06:00 [pubmed] PHST- 2016/02/02 06:00 [medline] AID - ehv043 [pii] AID - 10.1093/eurheartj/ehv043 [doi] PST - ppublish SO - Eur Heart J. 2015 May 1;36(17):1012-22. doi: 10.1093/eurheartj/ehv043. Epub 2015 Feb 18. PMID- 25994465 OWN - NLM STAT- MEDLINE DCOM- 20150708 LR - 20151119 IS - 1827-6806 (Print) IS - 1827-6806 (Linking) VI - 16 IP - 5 DP - 2015 May TI - [Mutations of APOC3 gene, metabolism of triglycerides and reduction of ischemic cardiovascular events]. PG - 289-94 LID - 10.1714/1870.20430 [doi] AB - A direct relationship between high plasma triglyceride (TG) levels and increased risk of cardiovascular disease has been shown in several studies. TG are present in the blood associated with different lipoprotein classes, including hepatically-derived very low density lipoproteins (VLDL) and intestinally-derived chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG, releasing free fatty acids that accumulate in peripheral tissues and remnant lipoproteins, that are then cleared by the liver. LPL activity is finely modulated by several cofactors, including apolipoprotein C-III (apoC-III) which acts as a LPL inhibitor. The key role of apoCIII has been established in several studies: animal models lacking APOC3 gene exhibit reduced plasma TG levels, whereas the overexpression of APOC3 gene led to increased TG levels. In humans, several mutations in APOC3 gene have been identified, leading to lower apoC-III levels and associated with reduced plasma TG levels. Recently, these mutations were found to be associated with a reduced risk for cardiovascular ischemia and coronary heart disease, thus confirming the negative role of apoC-III in TG metabolism and suggesting apoC-III as possible therapeutic target for the management of hypertriglyceridemia. FAU - Pirillo, Angela AU - Pirillo A FAU - Catapano, Alberico Luigi AU - Catapano AL LA - ita PT - English Abstract PT - Journal Article TT - Mutazioni del gene APOC3, metabolismo dei trigliceridi e riduzione di eventi ischemici cardiovascolari. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 0 (Apolipoprotein C-III) RN - 0 (Biomarkers) RN - 0 (Cholesterol, LDL) RN - 0 (Triglycerides) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Apolipoprotein C-III/blood/*genetics MH - Biomarkers/blood MH - Cholesterol, LDL/blood MH - Coronary Disease/blood/genetics MH - Humans MH - Lipoprotein Lipase/blood MH - Liver/metabolism MH - *Mutation MH - Myocardial Ischemia/*blood/*genetics/metabolism/prevention & control MH - Triglycerides/*blood EDAT- 2015/05/23 06:00 MHDA- 2015/07/15 06:00 CRDT- 2015/05/22 06:00 PHST- 2015/05/22 06:00 [entrez] PHST- 2015/05/23 06:00 [pubmed] PHST- 2015/07/15 06:00 [medline] AID - 10.1714/1870.20430 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2015 May;16(5):289-94. doi: 10.1714/1870.20430. PMID- 25927920 OWN - NLM STAT- MEDLINE DCOM- 20160415 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 4 DP - 2015 TI - IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population. PG - e0122414 LID - 10.1371/journal.pone.0122414 [doi] AB - Inducible degrader of the low density lipoprotein receptor (IDOL), is an E3 ubiquitin ligase that negatively modulates low density lipoprotein receptor (LDL-R) expression. Genome-wide association studies (GWAS) indicated that genetic variants in IDOL gene contributes to variation in LDL-C plasma levels and the detailed analysis of a specific locus resulted in the identification of the functional common single nucleotide polymorphism (SNP) rs9370867 (c.G1025A, p.N342S) associates with increased LDL-R degradation and increased LDL-C levels. These findings, however, were not confirmed in two other independent cohorts and no data about the impact of this variant on atherosclerosis progression and cardiovascular risk are available. Aim of this study was to investigate the association between a functional variant in IDOL and atherosclerosis progression in an Italian general population. 1384 subjects enrolled in the PLIC study (Progression of Lesions in the Intima of Carotid) were genotyped by Q-PCR allelic discrimination and the association with anthropometric parameters, plasma lipids and the carotid intima media thickness (cIMT) and the impact on cardiovascular disease (CVD) incidence were investigated. The N342S variant was not associated with changes of the plasma lipid profile among GG, AG or AA carriers, including total cholesterol (249+/-21, 249+/-19 and 248+/-21 mg/dl respectively), LDL-C (158+/-25, 161+/-22 and 160+/-23 mg/dL), cIMT (0.74+/-0.14, 0.75+/-0.17 and 0.77+/-0.15 mm) and CVD incidence. In agreement, the expression of LDLR and the uptake of LDL was similar in macrophages derived from GG and AA carriers. Taken together our findings indicate that the N342S variant does not impact plasma lipid profile and is not associated with atherosclerosis progression and CVD in the general population, suggesting that other variants in the IDOL gene might be functionally linked with cholesterol metabolism. FAU - Dhyani, Ashish AU - Dhyani A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Tibolla, Gianpaolo AU - Tibolla G AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; I.R.C.C.S MultiMedica, Milan, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B., Italy. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B., Italy. FAU - Pellegatta, Fabio AU - Pellegatta F AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B., Italy. FAU - Grigore, Liliana AU - Grigore L AD - I.R.C.C.S MultiMedica, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B., Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B., Italy; The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, United Kingdom. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; I.R.C.C.S MultiMedica, Milan, Italy. LA - eng GR - GGP13002/Telethon/Italy PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150430 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Cholesterol, LDL) RN - 0 (LDLR protein, human) RN - 0 (Receptors, LDL) RN - EC 2.3.2.27 (MYLIP protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Aged MH - Atherosclerosis/diagnostic imaging/epidemiology/*genetics/metabolism MH - *Carotid Intima-Media Thickness MH - Cholesterol, LDL/blood/genetics MH - Female MH - Humans MH - Incidence MH - Italy/epidemiology MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Proteolysis MH - Receptors, LDL/genetics/metabolism MH - Ubiquitin-Protein Ligases/*genetics/metabolism PMC - PMC4415795 EDAT- 2015/05/01 06:00 MHDA- 2016/04/16 06:00 CRDT- 2015/05/01 06:00 PHST- 2014/11/07 00:00 [received] PHST- 2015/02/20 00:00 [accepted] PHST- 2015/05/01 06:00 [entrez] PHST- 2015/05/01 06:00 [pubmed] PHST- 2016/04/16 06:00 [medline] AID - 10.1371/journal.pone.0122414 [doi] AID - PONE-D-14-49577 [pii] PST - epublish SO - PLoS One. 2015 Apr 30;10(4):e0122414. doi: 10.1371/journal.pone.0122414. eCollection 2015. PMID- 25914523 OWN - NLM STAT- MEDLINE DCOM- 20160913 LR - 20181113 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 9 DP - 2015 TI - Update on the management of severe hypertriglyceridemia--focus on free fatty acid forms of omega-3. PG - 2129-37 LID - 10.2147/DDDT.S67551 [doi] AB - High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases, often associated with anomalies in other lipids or lipoproteins. Hypertriglyceridemia (HTG), particularly at very high levels, significantly increases also the risk of acute pancreatitis. Thus, interventions to lower TG levels are required to reduce the risk of pancreatitis and cardiovascular disease. Several strategies may be adopted for TG reduction, including lifestyle changes and pharmacological interventions. Among the available drugs, the most commonly used for HTG are fibrates, nicotinic acid, and omega-3 polyunsaturated fatty acids (usually a mixture of eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA). These last are available under different concentrated formulations containing high amounts of omega-3 fatty acids, including a mixture of EPA and DHA or pure EPA. The most recent formulation contains a free fatty acid (FFA) form of EPA and DHA, and exhibits a significantly higher bioavailability compared with the ethyl ester forms contained in the other formulations. This is due to the fact that the ethyl ester forms, to be absorbed, need to be hydrolyzed by the pancreatic enzymes that are secreted in response to fat intake, while the FFA do not. This higher bioavailability translates into a higher TG-lowering efficacy compared with the ethyl ester forms at equivalent doses. Omega-3 FFA are effective in reducing TG levels and other lipids in hypertriglyceridemic patients as well as in high cardiovascular risk patients treated with statins and residual HTG. Currently, omega-3 FFA formulation is under evaluation to establish whether, in high cardiovascular risk subjects, the addition of omega-3 to statin therapy may prevent or reduce major cardiovascular events. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy ; IRCCS Multimedica, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS Multimedica, Milan, Italy ; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20150410 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Fatty Acids, Omega-3) SB - IM MH - Cardiovascular Diseases/diet therapy/drug therapy MH - Fatty Acids, Omega-3/administration & dosage/*chemistry/*therapeutic use MH - Humans MH - Hypertriglyceridemia/*diet therapy/drug therapy PMC - PMC4401332 OTO - NOTNLM OT - docosahexaenoic acid OT - eicosapentaenoic acid OT - hypertriglyceridemia OT - omega-3 fatty acids EDAT- 2015/04/29 06:00 MHDA- 2016/09/14 06:00 CRDT- 2015/04/28 06:00 PHST- 2015/04/28 06:00 [entrez] PHST- 2015/04/29 06:00 [pubmed] PHST- 2016/09/14 06:00 [medline] AID - 10.2147/DDDT.S67551 [doi] AID - dddt-9-2129 [pii] PST - epublish SO - Drug Des Devel Ther. 2015 Apr 10;9:2129-37. doi: 10.2147/DDDT.S67551. eCollection 2015. PMID- 25040775 OWN - NLM STAT- MEDLINE DCOM- 20150601 LR - 20170922 IS - 1365-2796 (Electronic) IS - 0954-6820 (Linking) VI - 277 IP - 4 DP - 2015 Apr TI - Telomere shortening over 6 years is associated with increased subclinical carotid vascular damage and worse cardiovascular prognosis in the general population. PG - 478-87 LID - 10.1111/joim.12282 [doi] AB - INTRODUCTION: Leucocyte telomere length (LTL) is an important determinant of telomere function and cellular replicative capacity. The aim of the present study was to examine prospectively the associations between telomere shortening (TS) and both the progression of atherosclerosis and the incidence of cardiovascular events (CVEs). MATERIALS AND METHODS: Leucocyte telomere length was measured by quantitative polymerase chain reaction to determine the ratio of telomere length to single-copy gene (T/S) in 768 subjects (462 female and 306 male) enrolled in a large general population survey [the Progressione della Lesione Intimale Carotidea (PLIC study)]. Common carotid artery intima-media thickness was determined at baseline and after 6 years of follow-up, and the associations between TS and the progression of atherosclerosis and incidence of CVEs were evaluated. RESULTS: Mean LTL was 1.25 +/- 0.92 T/S (median 1.14) at baseline and 0.70 +/- 0.37 T/S (median 0.70) after 6 years of follow-up. Median 6-year LTL change was -0.46 T/S [interquartile range (IQR) -0.57 to 1.06], equating to -0.078 T/S [IQR(-0.092 to 0.176)] per year. Of note, telomere lengthening occurred in 30.4% of subjects. After adjustment for classical cardiovascular disease (CVD) risk factors (age, gender, smoking, physical activity, alcohol consumption, systolic blood pressure, glucose levels, lipid profile and therapies), TS was associated with incident subclinical carotid vascular damage [hazard ratio (HR) 5.19, 95% confidence interval (CI) 1.20-22.4, P = 0.028]. Finally, subjects in whom LTL shortened over time showed an increased risk of incident CVE, compared to those in whom LTL lengthened (HR 1.69, CI 1.02-2.78, P = 0.041). CONCLUSION: These data indicate that TS is associated with increased risk of subclinical carotid vascular damage and increased incidence of CVEs beyond CVD risk factors in the general population, whereas LTL lengthening is protective. CI - (c) 2014 The Association for the Publication of the Journal of Internal Medicine. FAU - Baragetti, A AU - Baragetti A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Palmen, J AU - Palmen J FAU - Garlaschelli, K AU - Garlaschelli K FAU - Grigore, L AU - Grigore L FAU - Pellegatta, F AU - Pellegatta F FAU - Tragni, E AU - Tragni E FAU - Catapano, A L AU - Catapano AL FAU - Humphries, S E AU - Humphries SE FAU - Norata, G D AU - Norata GD FAU - Talmud, P J AU - Talmud PJ LA - eng GR - GGP13002/Telethon/Italy GR - RG/08/008/25291/British Heart Foundation/United Kingdom GR - PG08/008/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140719 PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 SB - IM MH - Carotid Artery Diseases/*pathology MH - Disease Progression MH - Female MH - Humans MH - Male MH - Polymerase Chain Reaction MH - Prognosis MH - ROC Curve MH - Telomere/chemistry/*pathology OTO - NOTNLM OT - ageing OT - cardiovascular disease OT - intima-media thickness OT - leucocytes telomere length OT - telomere shortening EDAT- 2014/07/22 06:00 MHDA- 2015/06/02 06:00 CRDT- 2014/07/22 06:00 PHST- 2014/07/22 06:00 [entrez] PHST- 2014/07/22 06:00 [pubmed] PHST- 2015/06/02 06:00 [medline] AID - 10.1111/joim.12282 [doi] PST - ppublish SO - J Intern Med. 2015 Apr;277(4):478-87. doi: 10.1111/joim.12282. Epub 2014 Jul 19. PMID- 25614280 OWN - NLM STAT- MEDLINE DCOM- 20160412 LR - 20181113 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 35 IP - 3 DP - 2015 Mar TI - Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. PG - 689-99 LID - 10.1161/ATVBAHA.114.304549 [doi] AB - OBJECTIVE: Lp(a) is an independent, causal, genetic risk factor for cardiovascular disease and aortic stenosis. Current pharmacological lipid-lowering therapies do not optimally lower Lp(a), particularly in patients with familial hypercholesterolemia (FH). APPROACH AND RESULTS: In 4 phase III trials, 382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks. Populations included homozygous FH, heterozygous FH with concomitant coronary artery disease (CAD), severe hypercholesterolemia, and hypercholesterolemia at high risk for CAD. Lp(a) was measured 8x between baseline and week 28 inclusive. Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 and >50 mg/dL, respectively. In the pooled analysis, the mean percent decrease (median, interquartile range in Lp(a) at 28 weeks was significantly greater in the mipomersen group compared with placebo (-26.4 [-42.8, -5.4] versus -0.0 [-10.7, 15.3]; P<0.001). In the mipomersen group in patients with Lp(a) levels >30 or >50 mg/dL, attainment of Lp(a) values C and c.3697-1G > A). CHOK1H8 cells expressing minigenes harbouring the mutations showed that these two mutations were associated with the retention of intron 23 and skipping of exon 24, resulting in two truncated apoB fragments of approximate size of 26-28 % of ApoB-100 and the total absence of apoB. CONCLUSION: We describe the first case of Ho-FHBL due to two splicing mutations affecting both the donor and the acceptor splice sites of the same intron of the APOB gene occurring in the same patient. The clinical management of the proband is discussed and a review of the clinical and genetic features of the published Ho-FHBL cases is reported. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Cefalu, Angelo B AU - Cefalu AB AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Universita degli Studi di Palermo, Italy. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacology and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. FAU - Ghiglioni, Daniele G AU - Ghiglioni DG AD - Department of Paediatrics, Melloni Hospital, Milano, Italy. FAU - Noto, Davide AU - Noto D AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Universita degli Studi di Palermo, Italy. FAU - Uboldi, Patrizia AU - Uboldi P AD - Department of Pharmacology and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - Department of Pharmacology and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacology and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. FAU - Spina, Rossella AU - Spina R AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Universita degli Studi di Palermo, Italy. FAU - Valenti, Vincenza AU - Valenti V AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Universita degli Studi di Palermo, Italy. FAU - Pederiva, Cristina AU - Pederiva C AD - Dipartimento di Scienze della Salute, Universita degli Studi di Milano, Italy. FAU - Riva, Enrica AU - Riva E AD - Dipartimento di Scienze della Salute, Universita degli Studi di Milano, Italy. FAU - Terracciano, Luigi AU - Terracciano L AD - Department of Paediatrics, Melloni Hospital, Milano, Italy. FAU - Zoja, Alexa AU - Zoja A AD - Department of Paediatrics, Melloni Hospital, Milano, Italy. FAU - Grigore, Liliana AU - Grigore L AD - Department of Pharmacology and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy; IRCCS Multimedica, Milano, Italy. FAU - Averna, Maurizio R AU - Averna MR AD - Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), Universita degli Studi di Palermo, Italy. Electronic address: maurizio.averna@unipa.it. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacology and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy; IRCCS Multimedica, Milano, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng GR - GGP13002/Telethon/Italy PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150119 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (APOB protein, human) RN - 0 (Apolipoprotein B-100) RN - 0 (Cholesterol, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Abetalipoproteinemia/genetics MH - Adult MH - Alternative Splicing MH - Apolipoprotein B-100/*genetics MH - Cholesterol/blood MH - Cholesterol, LDL/blood MH - DNA Mutational Analysis MH - Female MH - *Homozygote MH - Humans MH - Hypobetalipoproteinemias/*diagnosis/*genetics MH - Infant MH - Introns MH - Male MH - *Mutation OTO - NOTNLM OT - Acanthocytosis OT - Apolipoprotein B OT - Homozygous familial hypobetalipoproteinemia EDAT- 2015/01/27 06:00 MHDA- 2016/04/01 06:00 CRDT- 2015/01/26 06:00 PHST- 2014/09/28 00:00 [received] PHST- 2014/12/21 00:00 [revised] PHST- 2015/01/13 00:00 [accepted] PHST- 2015/01/26 06:00 [entrez] PHST- 2015/01/27 06:00 [pubmed] PHST- 2016/04/01 06:00 [medline] AID - S0021-9150(15)00048-9 [pii] AID - 10.1016/j.atherosclerosis.2015.01.014 [doi] PST - ppublish SO - Atherosclerosis. 2015 Mar;239(1):209-17. doi: 10.1016/j.atherosclerosis.2015.01.014. Epub 2015 Jan 19. PMID- 27326442 OWN - NLM STAT- MEDLINE DCOM- 20160805 LR - 20170922 IS - 1016-5169 (Print) IS - 1016-5169 (Linking) VI - 43 Suppl 1 DP - 2015 Mar TI - [Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society]. PG - 1-14 FAU - Cuchel, Marina AU - Cuchel M FAU - Bruckert, Eric AU - Bruckert E FAU - Ginsberg, Henry N AU - Ginsberg HN FAU - Raal, Frederick J AU - Raal FJ FAU - Santos, Raul D AU - Santos RD FAU - Hegele, Robert A AU - Hegele RA FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA FAU - Nordestgaard, Borge G AU - Nordestgaard BG FAU - Descamps, Olivier S AU - Descamps OS FAU - Steinhagen-Thiessen, Elisabeth AU - Steinhagen-Thiessen E FAU - Tybjaerg-Hansen, Anne AU - Tybjaerg-Hansen A FAU - Watts, Gerald F AU - Watts GF FAU - Averna, Maurizio AU - Averna M FAU - Boileau, Catherine AU - Boileau C FAU - Boren, Jan AU - Boren J FAU - Catapano, Alberico L AU - Catapano AL FAU - Defesche, Joep C AU - Defesche JC FAU - Hovingh, G Kees AU - Hovingh GK FAU - Humphries, Steve E AU - Humphries SE FAU - Kovanen, Petri T AU - Kovanen PT FAU - Masana, Luis AU - Masana L FAU - Pajukanta, Paivi AU - Pajukanta P FAU - Parhofer, Klaus G AU - Parhofer KG FAU - Ray, Kausik K AU - Ray KK FAU - Stalenhoef, Anton F H AU - Stalenhoef AF FAU - Stroes, Erik AU - Stroes E FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Wiegman, Albert AU - Wiegman A FAU - Wiklund, Olov AU - Wiklund O FAU - Chapman, M John AU - Chapman MJ CN - Avrupa Ateroskleroz Dernegi Ailevi Hiperkolesterolemi Uzlasi Paneli LA - tur GR - RG/08/008/25291/British Heart Foundation/United Kingdom PT - Journal Article TT - Homozigot ailevi hiperkolesterolemi: klinisyenlerin taniyi ve klinik yonetimi gelistirmelerine yonelik yeni anlayislar ve rehberlik. Avrupa Ateroskleroz Dernegi'nin Ailevi Hiperkolesterolemi Uzerine Uzlasi Paneli yazili gorusu. PL - Turkey TA - Turk Kardiyol Dern Ars JT - Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir JID - 9426239 SB - IM MH - Consensus MH - Europe MH - Humans MH - *Hyperlipoproteinemia Type II/diagnosis/therapy MH - Practice Guidelines as Topic IR - Cuchel M FIR - Cuchel, Marina IR - Bruckert E FIR - Bruckert, Eric IR - Chapman M FIR - Chapman, M John IR - Descamps OS FIR - Descamps, Olivier S IR - Ginsberg HN FIR - Ginsberg, Henry N IR - Hegele RA FIR - Hegele, Robert A IR - Kuivenhoven JA FIR - Kuivenhoven, Jan Albert IR - Nordestgaard BG FIR - Nordestgaard, Borge G IR - Raal FJ FIR - Raal, Frederick J IR - Santos RD FIR - Santos, Raul D IR - Steinhagen-Thiessen E FIR - Steinhagen-Thiessen, Elisabeth IR - Tybjaerg-Hansen A FIR - Tybjaerg-Hansen, Anne IR - Watts GF FIR - Watts, Gerald F IR - Chapman M FIR - Chapman, M John IR - Ginsberg HN FIR - Ginsberg, Henry N IR - Averna M FIR - Averna, Maurizio IR - Boileau C FIR - Boileau, Catherine IR - Bore'n J FIR - Bore'n, Jan IR - Catapano AL FIR - Catapano, Alberico L IR - Defesche JC FIR - Defesche, Joep C IR - Hovingh G FIR - Hovingh, G Kees IR - Humphries SE FIR - Humphries, Steve E IR - Kovanen PT FIR - Kovanen, Petri T IR - Masana L FIR - Masana, Luis IR - Pajukanta P FIR - Pajukanta, Paivi IR - Parhofer KG FIR - Parhofer, Klaus G IR - Ray KK FIR - Ray, Kausik K IR - Stalenhoef AF FIR - Stalenhoef, Anton F H IR - Stroes E FIR - Stroes, Erik IR - Taskinen MR FIR - Taskinen, Marja-Riitta IR - Wiegman A FIR - Wiegman, Albert IR - Wiklund O FIR - Wiklund, Olov EDAT- 2015/03/01 00:00 MHDA- 2016/08/06 06:00 CRDT- 2016/06/22 06:00 PHST- 2016/06/22 06:00 [entrez] PHST- 2015/03/01 00:00 [pubmed] PHST- 2016/08/06 06:00 [medline] PST - ppublish SO - Turk Kardiyol Dern Ars. 2015 Mar;43 Suppl 1:1-14. PMID- 25659868 OWN - NLM STAT- MEDLINE DCOM- 20151028 LR - 20181202 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 17 DP - 2015 Feb TI - New insights on ezetimibe. Introduction. PG - 1 LID - 10.1016/S1567-5688(15)50001-9 [doi] LID - S1567-5688(15)50001-9 [pii] FAU - Catapano, Alberico L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milan, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Introductory Journal Article PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Biomarkers) RN - 0 (Lipids) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Animals MH - Anticholesteremic Agents/*therapeutic use MH - Azetidines/*therapeutic use MH - Biomarkers/blood MH - Dyslipidemias/blood/diagnosis/*drug therapy/etiology MH - Ezetimibe MH - Humans MH - Intestinal Absorption/drug effects MH - Intestinal Mucosa/metabolism MH - Intestines/drug effects MH - Lipids/*blood MH - Treatment Outcome EDAT- 2015/02/11 06:00 MHDA- 2015/10/29 06:00 CRDT- 2015/02/10 06:00 PHST- 2015/02/10 06:00 [entrez] PHST- 2015/02/11 06:00 [pubmed] PHST- 2015/10/29 06:00 [medline] AID - S1567-5688(15)50001-9 [pii] AID - 10.1016/S1567-5688(15)50001-9 [doi] PST - ppublish SO - Atheroscler Suppl. 2015 Feb;17:1. doi: 10.1016/S1567-5688(15)50001-9. PMID- 25522999 OWN - NLM STAT- MEDLINE DCOM- 20150415 LR - 20151119 IS - 0171-2004 (Print) IS - 0171-2004 (Linking) VI - 224 DP - 2015 TI - HDL in infectious diseases and sepsis. PG - 483-508 LID - 10.1007/978-3-319-09665-0_15 [doi] AB - During infection significant alterations in lipid metabolism and lipoprotein composition occur. Triglyceride and VLDL cholesterol levels increase, while reduced HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels are observed. More importantly, endotoxemia modulates HDL composition and size: phospholipids are reduced as well as apolipoprotein (apo) A-I, while serum amyloid A (SAA) and secretory phospholipase A2 (sPLA2) dramatically increase, and, although the total HDL particle number does not change, a significant decrease in the number of small- and medium-size particles is observed. Low HDL-C levels inversely correlate with the severity of septic disease and associate with an exaggerated systemic inflammatory response. HDL, as well as other plasma lipoproteins, can bind and neutralize Gram-negative bacterial lipopolysaccharide (LPS) and Gram-positive bacterial lipoteichoic acid (LTA), thus favoring the clearance of these products. HDLs are emerging also as a relevant player during parasitic infections, and a specific component of HDL, namely, apoL-1, confers innate immunity against trypanosome by favoring lysosomal swelling which kills the parasite. During virus infections, proteins associated with the modulation of cholesterol bioavailability in the lipid rafts such as ABCA1 and SR-BI have been shown to favor virus entry into the cells. Pharmacological studies support the benefit of recombinant HDL or apoA-I mimetics during bacterial infection, while apoL-1-nanobody complexes were tested for trypanosome infection. Finally, SR-BI antagonism represents a novel and forefront approach interfering with hepatitis C virus entry which is currently tested in clinical studies. From the coming years, we have to expect new and compelling observations further linking HDL to innate immunity and infections. FAU - Pirillo, Angela AU - Pirillo A AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Journal Article PT - Review PL - Germany TA - Handb Exp Pharmacol JT - Handbook of experimental pharmacology JID - 7902231 RN - 0 (Biomarkers) RN - 0 (Lipoproteins, HDL) SB - IM MH - Animals MH - Bacterial Infections/blood/immunology/*metabolism/microbiology MH - Biomarkers/blood MH - Host-Parasite Interactions MH - Host-Pathogen Interactions MH - Humans MH - Lipoproteins, HDL/blood/*metabolism MH - Parasitic Diseases/blood/immunology/*metabolism/parasitology MH - Sepsis/blood/immunology/*metabolism MH - Virus Diseases/blood/immunology/*metabolism/virology EDAT- 2014/12/20 06:00 MHDA- 2015/04/16 06:00 CRDT- 2014/12/20 06:00 PHST- 2014/12/20 06:00 [entrez] PHST- 2014/12/20 06:00 [pubmed] PHST- 2015/04/16 06:00 [medline] AID - 10.1007/978-3-319-09665-0_15 [doi] PST - ppublish SO - Handb Exp Pharmacol. 2015;224:483-508. doi: 10.1007/978-3-319-09665-0_15. PMID- 25444678 OWN - NLM STAT- MEDLINE DCOM- 20150904 LR - 20181113 IS - 1932-7420 (Electronic) IS - 1550-4131 (Linking) VI - 20 IP - 5 DP - 2014 Nov 4 TI - The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism. PG - 787-798 LID - S1550-4131(14)00401-X [pii] LID - 10.1016/j.cmet.2014.09.004 [doi] AB - Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By combining data from a GWAS screening in >100,000 individuals of European ancestry, mediator lipidomics, and functional validation studies in mice, we identify the AA metabolome as an important regulator of cholesterol homeostasis. Pharmacological modulation of AA metabolism by aspirin induced hepatic generation of leukotrienes (LTs) and lipoxins (LXs), thereby increasing hepatic expression of the bile salt export pump Abcb11. Induction of Abcb11 translated in enhanced reverse cholesterol transport, one key function of HDL. Further characterization of the bioactive AA-derivatives identified LX mimetics to lower plasma LDL-C. Our results define the AA metabolomeasconserved regulator of cholesterol metabolism, and identify AA derivatives as promising therapeutics to treat cardiovascular disease in humans. FAU - Demetz, Egon AU - Demetz E AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Schroll, Andrea AU - Schroll A AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Auer, Kristina AU - Auer K AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Heim, Christiane AU - Heim C AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Patsch, Josef R AU - Patsch JR AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Eller, Philipp AU - Eller P AD - Department of Internal Medicine, Angiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. FAU - Theurl, Markus AU - Theurl M AD - Department of Internal Medicine III, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Theurl, Igor AU - Theurl I AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Theurl, Milan AU - Theurl M AD - Department of Ophthalmology and Optometry, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Seifert, Markus AU - Seifert M AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Lener, Daniela AU - Lener D AD - Department of Internal Medicine III, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Stanzl, Ursula AU - Stanzl U AD - Department of Internal Medicine III, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Haschka, David AU - Haschka D AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Asshoff, Malte AU - Asshoff M AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Dichtl, Stefanie AU - Dichtl S AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Nairz, Manfred AU - Nairz M AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Huber, Eva AU - Huber E AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Stadlinger, Martin AU - Stadlinger M AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Moschen, Alexander R AU - Moschen AR AD - Department of Internal Medicine I, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Li, Xiaorong AU - Li X AD - Department of Pharmacology, Capital Medical University, Number 10 Xitoutiao, You An Men, 100069 Beijing, China. FAU - Pallweber, Petra AU - Pallweber P AD - Department of Pediatrics II, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. FAU - Scharnagl, Hubert AU - Scharnagl H AD - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. FAU - Stojakovic, Tatjana AU - Stojakovic T AD - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. FAU - Marz, Winfried AU - Marz W AD - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Department of Internal Medicine, Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; Synlab Academy, Harrlachweg 1, 68163 Mannheim, Germany. FAU - Kleber, Marcus E AU - Kleber ME AD - Department of Internal Medicine, Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - Center for the Study of Atherosclerosis, Bassini Hospital, via Gorki 50, 20092 Cinisello Balsamo Milan, Italy. FAU - Uboldi, Patrizia AU - Uboldi P AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy; IRCCS Multimedica, via Milanese 300, 20099 Sesto San Giovanni Milan, Italy. FAU - Stellaard, Frans AU - Stellaard F AD - Department of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands. FAU - Rudling, Mats AU - Rudling M AD - Department of Medicine and Department of Biosciences and Nutrition, Karolinska Institute at Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden. FAU - Kuba, Keiji AU - Kuba K AD - Department of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine, Akita University, 1-1 Tegata Gakuen-machi, 010-8502 Akita City, Japan. FAU - Imai, Yumiko AU - Imai Y AD - Department of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine, Akita University, 1-1 Tegata Gakuen-machi, 010-8502 Akita City, Japan. FAU - Arita, Makoto AU - Arita M AD - Department of Health Chemistry, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8654 Tokyo, Japan. FAU - Schuetz, John D AU - Schuetz JD AD - Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS313, Memphis, TN 38105, USA. FAU - Pramstaller, Peter P AU - Pramstaller PP AD - Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Drususallee 1, 39100 Bolzano, Italy-Affiliated Institute of the University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. FAU - Tietge, Uwe J F AU - Tietge UJF AD - Department of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands. FAU - Trauner, Michael AU - Trauner M AD - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. FAU - Norata, Giuseppe D AU - Norata GD AD - Center for the Study of Atherosclerosis, Bassini Hospital, via Gorki 50, 20092 Cinisello Balsamo Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy; The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen Mary University, 4 Newark Street, E1 2AT London, UK. FAU - Claudel, Thierry AU - Claudel T AD - Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. FAU - Hicks, Andrew A AU - Hicks AA AD - Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Drususallee 1, 39100 Bolzano, Italy-Affiliated Institute of the University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. FAU - Weiss, Guenter AU - Weiss G AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: guenter.weiss@i-med.ac.at. FAU - Tancevski, Ivan AU - Tancevski I AD - Department of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: ivan.tancevski@i-med.ac.at. LA - eng GR - GGP13002/Telethon/Italy GR - P30 CA021765/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Metab JT - Cell metabolism JID - 101233170 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Bile Acids and Salts) RN - 0 (Cholesterol, HDL) RN - 0 (Leukotrienes) RN - 27YG812J1I (Arachidonic Acid) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase) RN - EC 1.3.11.34 (ALOX5 protein, human) RN - R16CO5Y76E (Aspirin) SB - IM CIN - Cell Metab. 2014 Dec 2;20(6):935-7. PMID: 25470544 MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use MH - Arachidonate 5-Lipoxygenase/metabolism MH - Arachidonic Acid/*metabolism MH - Aspirin/therapeutic use MH - Atherosclerosis/drug therapy/metabolism MH - Bile Acids and Salts/metabolism MH - Cells, Cultured MH - Cholesterol/blood/*metabolism MH - Cholesterol, HDL/blood/metabolism MH - Humans MH - Leukotrienes/metabolism MH - Liver/drug effects/metabolism MH - *Metabolome MH - Mice MH - Mice, Inbred C57BL PMC - PMC4232508 EDAT- 2014/12/03 06:00 MHDA- 2015/09/05 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/06/25 00:00 [received] PHST- 2014/08/10 00:00 [revised] PHST- 2014/09/08 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/09/05 06:00 [medline] AID - S1550-4131(14)00401-X [pii] AID - 10.1016/j.cmet.2014.09.004 [doi] PST - ppublish SO - Cell Metab. 2014 Nov 4;20(5):787-798. doi: 10.1016/j.cmet.2014.09.004. PMID- 25299967 OWN - NLM STAT- MEDLINE DCOM- 20150817 LR - 20161125 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 237 IP - 1 DP - 2014 Nov TI - Combination therapy in dyslipidemia: where are we now? PG - 319-35 LID - 10.1016/j.atherosclerosis.2014.09.026 [doi] LID - S0021-9150(14)01428-2 [pii] AB - Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of cardiovascular disease: each 1.0 mmol/L (38.7 mg/dL) reduction in LDL-C reduces the incidence of major coronary events, coronary revascularizations, and ischemic stroke by approximately 20%. Statins are a well-established treatment option for dyslipidemia, with LDL-C reduction in the range of 27-55%. Several lipid goal-driven guidelines recommend reducing LDL-C to <2.59 mmol/L (100 mg/dL) or <1.81 mmol/L (70 mg/dL) in very high-risk patients. Many patients treated with statins do not reach these goals, and remain at risk of future cardiovascular events. The 2013 American College of Cardiology/American Heart Association guidelines move away from advocating LDL-C treatment targets with focus placed on identifying patients most likely to benefit from high-intensity or moderate-intensity statin therapy. While increasing the statin dose can prove efficacious in some patients, this approach typically offers limited additional LDL-C lowering, and is associated with increased incidence of adverse side effects. Indeed, this has led to the investigation of statins in combination with other lipid-modifying agents for the treatment of dyslipidemia. This review of the evidence for statin use in combination with fibrates, niacin, bile acid sequestrants, and the cholesterol absorption inhibitor, ezetimibe, in dyslipidemic patients at increased risk of cardiovascular disease, explores the impact of such combination therapies on lipids, attainment of lipid targets, inflammatory markers, and on cardiovascular outcomes and pathology. Additionally, new and emerging dyslipidemia treatments are summarized. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCSS Multimedia, Milan, Italy. FAU - Farnier, Michel AU - Farnier M AD - Point Medical, Dijon, France. FAU - Foody, JoAnne M AU - Foody JM AD - Division of Cardiovascular Medicine, Department of Internal Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Toth, Peter P AU - Toth PP AD - CGH Medical Centre, Sterling, IL, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Tomassini, Joanne E AU - Tomassini JE AD - Merck Sharp and Dohme Corp., Whitehouse Station, NJ, USA. FAU - Brudi, Philippe AU - Brudi P AD - Merck Sharp and Dohme Corp., Whitehouse Station, NJ, USA. FAU - Tershakovec, Andrew M AU - Tershakovec AM AD - Merck Sharp and Dohme Corp., Whitehouse Station, NJ, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140930 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Azetidines) RN - 0 (Bile Acids and Salts) RN - 0 (Cholesterol, LDL) RN - 0 (Fibric Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipids) RN - 2679MF687A (Niacin) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Azetidines/administration & dosage MH - Bile Acids and Salts/chemistry MH - Cardiovascular Diseases/drug therapy MH - Cholesterol/metabolism MH - Cholesterol, LDL/metabolism MH - Clinical Trials as Topic MH - Dyslipidemias/*drug therapy MH - Ezetimibe MH - Female MH - Fibric Acids/administration & dosage MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage MH - Inflammation/*blood MH - Lipids/*blood MH - Male MH - Niacin/administration & dosage MH - Patient Compliance MH - Proprotein Convertase 9 MH - Proprotein Convertases/blood MH - Serine Endopeptidases/blood MH - Treatment Outcome OTO - NOTNLM OT - Combination therapy OT - Ezetimibe OT - Fibrate OT - LDL-C OT - Niacin OT - PCSK9 OT - Statin EDAT- 2014/10/10 06:00 MHDA- 2015/08/19 06:00 CRDT- 2014/10/10 06:00 PHST- 2014/06/23 00:00 [received] PHST- 2014/09/08 00:00 [revised] PHST- 2014/09/08 00:00 [accepted] PHST- 2014/10/10 06:00 [entrez] PHST- 2014/10/10 06:00 [pubmed] PHST- 2015/08/19 06:00 [medline] AID - S0021-9150(14)01428-2 [pii] AID - 10.1016/j.atherosclerosis.2014.09.026 [doi] PST - ppublish SO - Atherosclerosis. 2014 Nov;237(1):319-35. doi: 10.1016/j.atherosclerosis.2014.09.026. Epub 2014 Sep 30. PMID- 25200803 OWN - NLM STAT- MEDLINE DCOM- 20150720 LR - 20141015 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 25 IP - 8 DP - 2014 Oct TI - Are generic and brand-name statins clinically equivalent? Evidence from a real data-base. PG - 745-50 LID - 10.1016/j.ejim.2014.08.002 [doi] LID - S0953-6205(14)00235-0 [pii] AB - BACKGROUND: Use of generic drugs can help contain drug spending. However, there is concern among patients and physicians that generic drugs may be clinically inferior to brand-name ones. This study aimed to compare patients treated with generic and brand-name statins in terms of therapeutic interruption and cardiovascular (CV) outcomes. METHODS: 13,799 beneficiaries of the health care system of Lombardy, Italy, aged 40 years or older who were newly treated with generic or brand-name simvastatin during 2008, were followed until 2011 for the occurrence of two outcomes: 1) therapeutic discontinuation and 2) hospitalization for CV events. Hazard ratios (HR) associated with use of generic or brand-name at starting therapy (intention-to-treat analysis) and during follow-up (as-treated analysis) were estimated by fitting proportional hazard Cox models. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. RESULTS: Patients who started on generic did not experience a different risk of discontinuation (HR: 0.98; 95% CI 0.94 to 1.02) nor of CV outcomes (HR: 0.98; 95% CI 0.79 to 1.22) from those starting on brand-name. Patients who spent >75% of time of follow-up with statin available on generics did not experience a different risk of discontinuation (HR: 0.94; 95% CI 0.87 to 1.01), nor of CV outcomes (HR: 1.06; 95% CI 0.83 to 1.34), compared with those who mainly or only used brand-name statin. CONCLUSIONS: Our findings do not support the notion that in the real world clinical practice brand-name statins are superior to generics for keeping therapy and preventing CV outcomes. CI - Copyright (c) 2014. Published by Elsevier B.V. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. FAU - Soranna, Davide AU - Soranna D AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy; IRCSS Istituto Auxologico Italiano, Milan, Italy. FAU - Arfe, Andrea AU - Arfe A AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy. FAU - Casula, Manuela AU - Casula M AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Region Lombardia, Milan, Italy. FAU - Mancia, Giuseppe AU - Mancia G AD - IRCSS Istituto Auxologico Italiano, Milan, Italy; Department of Health Science, University of Milano-Bicocca, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy; IRCSS Multimedica, Sesto San Giovanni, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140906 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - AGG2FN16EV (Simvastatin) SB - IM MH - Aged MH - Cardiovascular Diseases/*drug therapy MH - Female MH - Hospitalization/statistics & numerical data MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacokinetics MH - Male MH - Middle Aged MH - Simvastatin/*pharmacokinetics MH - Therapeutic Equivalency OTO - NOTNLM OT - Brand-name OT - Cardiovascular events OT - Databases OT - Discontinuation OT - Generic OT - Statins EDAT- 2014/09/10 06:00 MHDA- 2015/07/21 06:00 CRDT- 2014/09/10 06:00 PHST- 2014/05/26 00:00 [received] PHST- 2014/08/08 00:00 [revised] PHST- 2014/08/10 00:00 [accepted] PHST- 2014/09/10 06:00 [entrez] PHST- 2014/09/10 06:00 [pubmed] PHST- 2015/07/21 06:00 [medline] AID - S0953-6205(14)00235-0 [pii] AID - 10.1016/j.ejim.2014.08.002 [doi] PST - ppublish SO - Eur J Intern Med. 2014 Oct;25(8):745-50. doi: 10.1016/j.ejim.2014.08.002. Epub 2014 Sep 6. PMID- 24835295 OWN - NLM STAT- MEDLINE DCOM- 20150413 LR - 20181202 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 88 DP - 2014 Oct TI - Statins and skeletal muscles toxicity: from clinical trials to everyday practice. PG - 107-13 LID - 10.1016/j.phrs.2014.04.012 [doi] LID - S1043-6618(14)00052-8 [pii] AB - The mechanism(s) underlying the occurrence of statin-induced myopathy are ill defined, but the results of observational studies and clinical trials provide compelling evidence that skeletal muscle toxicity is a frequent, dose-dependent, adverse event associated with all statins. It has been suggested that reduced availability of metabolites produced by the mevalonate pathway rather than intracellular cholesterol lowering per se might be the primary trigger of toxicity, however other alternative explanations have gained credibility in recent years. Aim of this review is: (i) to describe the molecular mechanisms associated to statin induced myopathy including defects in isoprenoids synthesis followed by altered prenylation of small GTPase, such as Ras and Rab proteins; (ii) to present the emerging aspects on pharmacogenetics, including CYP3A4, OATP1B1 and glycine amidinotransferase (GATM) polymorphisms impacting either statin bioavailability or creatine synthesis; (iii) to summarize the available epidemiological evidences; and (iii) to discuss the concepts that would be of interest to the clinicians for the daily management of patients with statin induced myopathy. The interplay between drug-environment and drug-drug interaction in the context of different genetic settings contribute to statins and skeletal muscles toxicity. Until specific assays/algorithms able to combine genetic scores with drug-drug-environment interaction to identify patients at risk of myopathies will become available, clinicians should continue to monitor carefully patients on polytherapy which include statins and be ready to reconsider dose, statin or switching to alternative treatments. The beneficial effects of adding agents to provide the muscle with the metabolites, such as CoQ10, affected by statin treatment will also be addressed. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Center for the Study of Atherosclerosis, Societa Italiana Studio Aterosclerosi, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Tibolla, Gianpaolo AU - Tibolla G AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; I.R.C.C.S. Multimedica, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; I.R.C.C.S. Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20140513 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Liver-Specific Organic Anion Transporter 1) RN - 0 (Organic Anion Transporters) RN - 0 (SLCO1B1 protein, human) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) SB - IM MH - Animals MH - Cytochrome P-450 Enzyme System/genetics MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/pharmacokinetics MH - Liver-Specific Organic Anion Transporter 1 MH - Muscle, Skeletal/drug effects MH - Muscular Diseases/*chemically induced/drug therapy/epidemiology/genetics MH - Organic Anion Transporters/genetics OTO - NOTNLM OT - Muscle toxicity OT - Myopathy OT - Pharmacogenetics OT - Statins EDAT- 2014/05/20 06:00 MHDA- 2015/04/14 06:00 CRDT- 2014/05/20 06:00 PHST- 2013/11/06 00:00 [received] PHST- 2014/04/23 00:00 [revised] PHST- 2014/04/27 00:00 [accepted] PHST- 2014/05/20 06:00 [entrez] PHST- 2014/05/20 06:00 [pubmed] PHST- 2015/04/14 06:00 [medline] AID - S1043-6618(14)00052-8 [pii] AID - 10.1016/j.phrs.2014.04.012 [doi] PST - ppublish SO - Pharmacol Res. 2014 Oct;88:107-13. doi: 10.1016/j.phrs.2014.04.012. Epub 2014 May 13. PMID- 25008143 OWN - NLM STAT- MEDLINE DCOM- 20150707 LR - 20181113 IS - 2567-689X (Electronic) IS - 0340-6245 (Linking) VI - 112 IP - 4 DP - 2014 Oct TI - MiR-143/145 deficiency attenuates the progression of atherosclerosis in Ldlr-/-mice. PG - 796-802 LID - 10.1160/TH13-11-0905 [doi] AB - The miR-143/145 cluster regulates VSMC specific gene expression, thus controlling differentiation, plasticity and contractile function, and promoting the VSMC phenotypic switch from a contractile/non-proliferative to a migrating/proliferative state. More recently increased miR-145 expression was observed in human carotid atherosclerotic plaques from symptomatic patients. The goal of this study was to investigate the contribution of miR-143/145 during atherogenesis by generating mice lacking miR-143/145 on an Ldlr-deficient background. Ldlr-/- and Ldlr-/--miR-143/145-/- (DKO) were fed a Western diet (WD) for 16 weeks. At the end of the treatment, the lipid profile and the atherosclerotic lesions were assessed in both groups of mice. Absence of miR-143/145 significantly reduced atherosclerotic plaque size and macrophage infiltration. Plasma total cholesterol levels were lower in DKO and FLPC analysis showed decreased cholesterol content in VLDL and LDL fractions. Interestingly miR-143/145 deficiency per se resulted in increased hepatic and vascular ABCA1 expression. We further confirmed the direct regulation of miR-145 on ABCA1 expression by qRT-PCR, Western blotting and 3'UTR-luciferase reporter assays. In summary, miR-143/145 deficiency significantly reduces atherosclerosis in mice. Therapeutic inhibition of miR-145 might be useful for treating atherosclerotic vascular disease. FAU - Sala, Federica AU - Sala F FAU - Aranda, Juan F AU - Aranda JF FAU - Rotllan, Noemi AU - Rotllan N FAU - Ramirez, Cristina M AU - Ramirez CM FAU - Aryal, Binod AU - Aryal B FAU - Elia, Leonardo AU - Elia L FAU - Condorelli, Gianluigi AU - Condorelli G FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Fernandez-Hernando, Carlos AU - Fernandez-Hernando C AD - Carlos Fernandez-Hernando, Yale University School of Medicine, 522 10 Amistad Street, Amistad Research Building, Room 337c, New Haven, CT 06510, USA, Tel.: +1 203 737 4615, Fax: +1 203 737 2290, E-mail: carlos.fernandez@yale.edu. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Giuseppe Danilo Norata, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy, Tel.: +39 02 50318313, Fax: +39 02 50318386, E-mail: danilo.norata@unimi.it. LA - eng GR - R01 HL106063/HL/NHLBI NIH HHS/United States GR - R01 HL107953/HL/NHLBI NIH HHS/United States GR - R01HL106063/HL/NHLBI NIH HHS/United States GR - R01HL107953/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140710 PL - Germany TA - Thromb Haemost JT - Thrombosis and haemostasis JID - 7608063 RN - 0 (3' Untranslated Regions) RN - 0 (Lipids) RN - 0 (Lipoproteins, LDL) RN - 0 (MIRN145 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn143 microRNA, mouse) RN - 0 (Receptors, LDL) SB - IM CIN - Thromb Haemost. 2014 Oct;112(4):629. PMID: 25208868 EIN - Thromb Haemost. 2015 Jul;114(1):210. PMID: 26125660 MH - 3' Untranslated Regions MH - Animals MH - Atherosclerosis/*genetics/metabolism MH - Base Sequence MH - Carotid Arteries MH - Cell Differentiation MH - Cell Movement MH - Disease Progression MH - Female MH - Lipids/chemistry MH - Lipoproteins, LDL/metabolism MH - Macrophages/cytology MH - Male MH - Mice MH - Mice, Knockout MH - MicroRNAs/*genetics MH - Molecular Sequence Data MH - Muscle, Smooth, Vascular/cytology MH - Phenotype MH - Plaque, Atherosclerotic/genetics/metabolism MH - Receptors, LDL/*genetics PMC - PMC4180777 MID - NIHMS624675 OTO - NOTNLM OT - ABCA1 OT - atherosclerosis OT - miR-143/145 OT - smooth muscle cells EDAT- 2014/07/11 06:00 MHDA- 2015/07/08 06:00 CRDT- 2014/07/11 06:00 PHST- 2013/11/04 00:00 [received] PHST- 2014/05/14 00:00 [accepted] PHST- 2014/07/11 06:00 [entrez] PHST- 2014/07/11 06:00 [pubmed] PHST- 2015/07/08 06:00 [medline] AID - 13-11-0905 [pii] AID - 10.1160/TH13-11-0905 [doi] PST - ppublish SO - Thromb Haemost. 2014 Oct;112(4):796-802. doi: 10.1160/TH13-11-0905. Epub 2014 Jul 10. PMID- 25257077 OWN - NLM STAT- MEDLINE DCOM- 20150602 LR - 20140926 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 15 IP - 2 DP - 2014 Sep TI - Management of homozygous familial hypercholesterolaemia--unmet needs, updated recommendations, and clinical experience with the MTP inhibitor, lomitapide. Concluding comments. PG - 52 LID - 10.1016/j.atherosclerosissup.2014.07.001 [doi] LID - S1567-5688(14)00015-4 [pii] FAU - Catapano, Alberico L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milan, and IRCCS Multimedica, Via Balzaretti 9, 20133 Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (BMS201038) RN - 0 (Benzimidazoles) RN - 0 (Cholesterol, LDL) SB - IM MH - Benzimidazoles/*therapeutic use MH - Blood Component Removal/*methods MH - Cholesterol, LDL/blood MH - *Consensus MH - *Disease Management MH - Homozygote MH - Humans MH - Hyperlipoproteinemia Type II/blood/*therapy MH - *Life Style OTO - NOTNLM OT - Apheresis OT - Drug-drug interactions OT - Homozygous familial hypercholesterolaemia OT - Lomitapide OT - Transaminase elevations EDAT- 2014/09/27 06:00 MHDA- 2015/06/03 06:00 CRDT- 2014/09/27 06:00 PHST- 2014/09/27 06:00 [entrez] PHST- 2014/09/27 06:00 [pubmed] PHST- 2015/06/03 06:00 [medline] AID - S1567-5688(14)00015-4 [pii] AID - 10.1016/j.atherosclerosissup.2014.07.001 [doi] PST - ppublish SO - Atheroscler Suppl. 2014 Sep;15(2):52. doi: 10.1016/j.atherosclerosissup.2014.07.001. PMID- 25257072 OWN - NLM STAT- MEDLINE DCOM- 20150602 LR - 20140926 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 15 IP - 2 DP - 2014 Sep TI - New strategies for the management of patients with homozygous familial hypercholesterolaemia. PG - 17-8 LID - 10.1016/j.atherosclerosissup.2014.07.002 [doi] LID - S1567-5688(14)00016-6 [pii] FAU - Catapano, Alberico L AU - Catapano AL AD - Institute of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 and IRCCS Multimedica Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Editorial PT - Introductory Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 SB - IM MH - *Disease Management MH - Humans MH - Hyperlipoproteinemia Type II/*therapy MH - *Practice Guidelines as Topic OTO - NOTNLM OT - Apheresis OT - Case studies OT - Consensus statement OT - Homozygous familial hypercholesterolaemia OT - Lomitapide OT - Patient survey EDAT- 2014/09/27 06:00 MHDA- 2015/06/03 06:00 CRDT- 2014/09/27 06:00 PHST- 2014/09/27 06:00 [entrez] PHST- 2014/09/27 06:00 [pubmed] PHST- 2015/06/03 06:00 [medline] AID - S1567-5688(14)00016-6 [pii] AID - 10.1016/j.atherosclerosissup.2014.07.002 [doi] PST - ppublish SO - Atheroscler Suppl. 2014 Sep;15(2):17-8. doi: 10.1016/j.atherosclerosissup.2014.07.002. PMID- 25053660 OWN - NLM STAT- MEDLINE DCOM- 20150512 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 35 IP - 32 DP - 2014 Aug 21 TI - Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. PG - 2146-57 LID - 10.1093/eurheartj/ehu274 [doi] AB - AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. CONCLUSION: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH. CI - (c) The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Cuchel, Marina AU - Cuchel M AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA mcuchel@mail.med.upenn.edu. FAU - Bruckert, Eric AU - Bruckert E AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Raal, Frederick J AU - Raal FJ AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Santos, Raul D AU - Santos RD AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Hegele, Robert A AU - Hegele RA AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Descamps, Olivier S AU - Descamps OS AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Steinhagen-Thiessen, Elisabeth AU - Steinhagen-Thiessen E AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Tybjaerg-Hansen, Anne AU - Tybjaerg-Hansen A AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Watts, Gerald F AU - Watts GF AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Averna, Maurizio AU - Averna M AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Boileau, Catherine AU - Boileau C AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Boren, Jan AU - Boren J AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Catapano, Alberico L AU - Catapano AL AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Defesche, Joep C AU - Defesche JC AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Hovingh, G Kees AU - Hovingh GK AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Humphries, Steve E AU - Humphries SE AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Kovanen, Petri T AU - Kovanen PT AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Masana, Luis AU - Masana L AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Pajukanta, Paivi AU - Pajukanta P AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Parhofer, Klaus G AU - Parhofer KG AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Ray, Kausik K AU - Ray KK AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Stalenhoef, Anton F H AU - Stalenhoef AF AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Stroes, Erik AU - Stroes E AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Taskinen, Marja-Riitta AU - Taskinen MR AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Wiegman, Albert AU - Wiegman A AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Wiklund, Olov AU - Wiklund O AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. FAU - Chapman, M John AU - Chapman MJ AD - Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. CN - European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia LA - eng GR - MOP-79523/Canadian Institutes of Health Research/Canada GR - British Heart Foundation/United Kingdom GR - RG/08/008/25291/British Heart Foundation/United Kingdom GR - P01 HL028481/HL/NHLBI NIH HHS/United States GR - MOP-13430/Canadian Institutes of Health Research/Canada GR - R01 HL095056/HL/NHLBI NIH HHS/United States PT - Consensus Development Conference PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140722 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) SB - IM MH - Anticholesteremic Agents/therapeutic use MH - Arcus Senilis/etiology MH - Atherosclerosis/diagnosis MH - Blood Component Removal/methods MH - Cardiovascular Diseases/etiology MH - Cholesterol, LDL/metabolism MH - Diagnosis, Differential MH - Early Diagnosis MH - Gene Frequency/genetics MH - Genetic Heterogeneity MH - Homozygote MH - Humans MH - Hyperlipoproteinemia Type II/*diagnosis/genetics/therapy MH - Liver Transplantation/methods MH - Mutation/genetics MH - Pedigree MH - Phenotype MH - Practice Guidelines as Topic MH - Xanthomatosis/etiology PMC - PMC4139706 OTO - NOTNLM OT - Diagnosis OT - Ezetimibe OT - Genetics OT - Homozygous familial hypercholesterolaemia OT - Lipoprotein apheresis OT - Lomitapide OT - Mipomersen OT - Phenotypic heterogeneity OT - Statins IR - Chapman M FIR - Chapman, M John IR - Ginsberg HN FIR - Ginsberg, Henry N IR - Averna M FIR - Averna, Maurizio IR - Boileau C FIR - Boileau, Catherine IR - Boren J FIR - Boren, Jan IR - Catapano AL FIR - Catapano, Alberico L IR - Defesche JC FIR - Defesche, Joep C IR - Hovingh G FIR - Hovingh, G Kees IR - Humphries SE FIR - Humphries, Steve E IR - Kovanen PT FIR - Kovanen, Petri T IR - Masana L FIR - Masana, Luis IR - Pajukanta P FIR - Pajukanta, Paivi IR - Parhofer KG FIR - Parhofer, Klaus G IR - Ray KK FIR - Ray, Kausik K IR - Stalenhoef AF FIR - Stalenhoef, Anton F H IR - Stroes E FIR - Stroes, Erik IR - Taskinen MR FIR - Taskinen, Marja-Riitta IR - Wiegman A FIR - Wiegman, Albert IR - Wiklund O FIR - Wiklund, Olov EDAT- 2014/07/24 06:00 MHDA- 2015/05/13 06:00 CRDT- 2014/07/24 06:00 PHST- 2014/07/24 06:00 [entrez] PHST- 2014/07/24 06:00 [pubmed] PHST- 2015/05/13 06:00 [medline] AID - ehu274 [pii] AID - 10.1093/eurheartj/ehu274 [doi] PST - ppublish SO - Eur Heart J. 2014 Aug 21;35(32):2146-57. doi: 10.1093/eurheartj/ehu274. Epub 2014 Jul 22. PMID- 24917645 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20181202 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 35 IP - 30 DP - 2014 Aug 7 TI - Understanding IMPROVE-IT and the cardinal role of LDL-C lowering in CVD prevention. PG - 1996-2000 LID - 10.1093/eurheartj/ehu228 [doi] FAU - Laufs, Ulrich AU - Laufs U AD - Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Geb. 40, Universitatsklinikum des Saarlandes, Homburg/Saar D-66421, Germany ulrich.laufs@uks.eu. FAU - Descamps, Olivier S AU - Descamps OS AD - Lipid Clinic, Hopital de Jolimont, Haine-Saint-Paul, Belgium. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milano and Multimedica IRCCS, Milano, Italy. FAU - Packard, Chris J AU - Packard CJ AD - Glasgow Clinical Research Facility, Tennent Building, 38 Church Street, Western Infirmary, Glasgow G11 6NT, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Comment DEP - 20140610 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - AGG2FN16EV (Simvastatin) SB - IM CON - Am Heart J. 2008 Nov;156(5):826-32. PMID: 19061694 MH - Acute Coronary Syndrome/*drug therapy MH - Anticholesteremic Agents/*administration & dosage MH - Azetidines/*therapeutic use MH - Humans MH - Simvastatin/*administration & dosage EDAT- 2014/06/12 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/06/12 06:00 PHST- 2014/06/12 06:00 [entrez] PHST- 2014/06/12 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] AID - ehu228 [pii] AID - 10.1093/eurheartj/ehu228 [doi] PST - ppublish SO - Eur Heart J. 2014 Aug 7;35(30):1996-2000. doi: 10.1093/eurheartj/ehu228. Epub 2014 Jun 10. PMID- 24951539 OWN - NLM STAT- MEDLINE DCOM- 20150331 LR - 20181113 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 103 IP - 3 DP - 2014 Aug 1 TI - Novel concepts in HDL pharmacology. PG - 423-8 LID - 10.1093/cvr/cvu141 [doi] AB - High-density lipoproteins (HDL) are a target for drug development because of their proposed anti-atherogenic properties. In this review, we will briefly discuss the currently established drugs for increasing HDL-C, namely niacin and fibrates, and some of their limitations. Next, we will focus on novel alternative therapies that are currently being developed for raising HDL-C, such as CETP inhibitors. Finally, we will conclude with a review of novel drugs that are being developed for modulating the function of HDL based on HDL mimetics. Gaps in our knowledge and the challenges that will have to be overcome for these new HDL based therapies will also be discussed. CI - Published by Oxford University Press on behalf of the European Society of Cardiology 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US. FAU - Remaley, Alan T AU - Remaley AT AD - National Heart, Lung and Blood Institute, NIH, 10 Center Drive, Bldg. 10, Rm. 2C-433, Bethesda, MD, USA aremaley1@cc.nih.gov. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Milano, Italy Center for the Study of Atherosclerosis, Societa Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Milano, Italy IRCCS Multimedica, Milan, Italy. LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140620 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Biomarkers) RN - 0 (Cholesterol, HDL) RN - 0 (Hypolipidemic Agents) SB - IM MH - Animals MH - Biomarkers/blood MH - Cardiovascular Diseases/blood/etiology/*prevention & control MH - Cholesterol, HDL/*blood MH - Drug Design MH - Dyslipidemias/blood/complications/*drug therapy MH - Humans MH - Hypolipidemic Agents/adverse effects/*therapeutic use MH - Molecular Targeted Therapy MH - Treatment Outcome MH - Up-Regulation PMC - PMC4133558 OTO - NOTNLM OT - Atherosclerosis OT - Cardiovascular disease OT - Cholesterol OT - Drugs OT - HDL EDAT- 2014/06/22 06:00 MHDA- 2015/04/01 06:00 CRDT- 2014/06/22 06:00 PHST- 2014/06/22 06:00 [entrez] PHST- 2014/06/22 06:00 [pubmed] PHST- 2015/04/01 06:00 [medline] AID - cvu141 [pii] AID - 10.1093/cvr/cvu141 [doi] PST - ppublish SO - Cardiovasc Res. 2014 Aug 1;103(3):423-8. doi: 10.1093/cvr/cvu141. Epub 2014 Jun 20. PMID- 24935428 OWN - NLM STAT- MEDLINE DCOM- 20150331 LR - 20170922 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 103 IP - 3 DP - 2014 Aug 1 TI - HDL in innate and adaptive immunity. PG - 372-83 LID - 10.1093/cvr/cvu150 [doi] AB - During infections or acute conditions high-density lipoproteins cholesterol (HDL-C) levels decrease very rapidly and HDL particles undergo profound changes in their composition and function. These changes are associated with poor prognosis following endotoxemia or sepsis and data from genetically modified animal models support a protective role for HDL. The same is true for some parasitic infections, where the key player appears to be a specific and minor component of HDL, namely apoL-1. The ability of HDL to influence cholesterol availability in lipid rafts in immune cells results in the modulation of toll-like receptors, MHC-II complex, as well as B- and T-cell receptors, while specific molecules shuttled by HDL such as sphingosine-1-phosphate (S1P) contribute to immune cells trafficking. Animal models with defects associated with HDL metabolism and/or influencing cell cholesterol efflux present features related to immune disorders. All these functions point to HDL as a platform integrating innate and adaptive immunity. The aim of this review is to provide an overview of the connection between HDL and immunity in atherosclerosis and beyond. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author 2014. For permissions please email: journals.permissions@oup.com. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, via Balzaretti 9, Milan 20133, Italy IRCCS Multimedica, Milan, Italy alberico.catapano@unimi.it danilo.norata@unimi.it. FAU - Pirillo, Angela AU - Pirillo A AD - IRCCS Multimedica, Milan, Italy Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, via Balzaretti 9, Milan 20133, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, via Balzaretti 9, Milan 20133, Italy Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK alberico.catapano@unimi.it danilo.norata@unimi.it. LA - eng GR - GGP13002/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140615 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Cholesterol, HDL) RN - 0 (Inflammation Mediators) SB - IM MH - *Adaptive Immunity MH - Animals MH - Atherosclerosis/blood/immunology/prevention & control MH - Cholesterol, HDL/blood/chemistry/genetics/*immunology MH - Endotoxemia/blood/immunology/prevention & control MH - Humans MH - Immune System Diseases/blood/genetics/*immunology/prevention & control MH - Immunity, Cellular MH - *Immunity, Innate MH - Inflammation Mediators/blood/immunology MH - Parasitic Diseases/blood/immunology/prevention & control MH - Signal Transduction OTO - NOTNLM OT - HDL OT - Immunity OT - Lipid rafts OT - Macrophages EDAT- 2014/06/18 06:00 MHDA- 2015/04/01 06:00 CRDT- 2014/06/18 06:00 PHST- 2014/06/18 06:00 [entrez] PHST- 2014/06/18 06:00 [pubmed] PHST- 2015/04/01 06:00 [medline] AID - cvu150 [pii] AID - 10.1093/cvr/cvu150 [doi] PST - ppublish SO - Cardiovasc Res. 2014 Aug 1;103(3):372-83. doi: 10.1093/cvr/cvu150. Epub 2014 Jun 15. PMID- 24890632 OWN - NLM STAT- MEDLINE DCOM- 20150115 LR - 20181113 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 16 IP - 8 DP - 2014 Aug TI - HDL: to treat or not to treat? PG - 429 LID - 10.1007/s11883-014-0429-x [doi] AB - Several studies have shown an inverse relationship between HDL cholesterol (HDL-C) levels and the risk of cardiovascular disease. Low HDL-C levels are commonly present in subjects with diabetes, metabolic syndrome, or obesity. These observations have suggested that increasing HDL concentrations might help in decreasing the cardiovascular disease risk. However, despite initial positive results, some recent data from clinical trials with HDL-raising therapies failed to confirm this hypothesis; in addition, data from Mendelian randomization analyses showed that nucleotide polymorphisms associated with increased HDL-C levels did not decrease the risk of myocardial infarction, further challenging the concept that higher HDL-C levels will automatically translate into lower cardiovascular disease risk. Differences in the quality and distribution of HDL particles might partly explain these findings, and in agreement with this hypothesis, some observations have suggested that HDL subpopulation levels may be better predictors of cardiovascular disease than simple HDL-C levels. Thus, it is expected that increased HDL-C levels may be beneficial when associated with an improvement in HDL function, suggesting that pharmacological approaches able to correct or increase HDL functions might produce more reliable clinical benefits. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy, angela.pirillo@guest.unimi.it. FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) SB - IM MH - Anticholesteremic Agents/therapeutic use MH - Cardiovascular Diseases/*blood/etiology/*prevention & control MH - Cholesterol, HDL/*blood MH - Cholesterol, LDL/blood MH - Humans EDAT- 2014/06/04 06:00 MHDA- 2015/01/16 06:00 CRDT- 2014/06/04 06:00 PHST- 2014/06/04 06:00 [entrez] PHST- 2014/06/04 06:00 [pubmed] PHST- 2015/01/16 06:00 [medline] AID - 10.1007/s11883-014-0429-x [doi] PST - ppublish SO - Curr Atheroscler Rep. 2014 Aug;16(8):429. doi: 10.1007/s11883-014-0429-x. PMID- 24673475 OWN - NLM STAT- MEDLINE DCOM- 20150601 LR - 20181202 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 30 IP - 8 DP - 2014 Aug TI - Postprandial lipemia as a cardiometabolic risk factor. PG - 1489-503 LID - 10.1185/03007995.2014.909394 [doi] AB - High levels of fasting circulating triglycerides (TG) represent an independent risk factor for cardiovascular disease. In western countries, however, people spend most time in postprandial conditions, with continuous fluctuation of lipemia due to increased levels of TG-rich lipoproteins (TRLs), including chylomicrons (CM), very low density lipoproteins (VLDL), and their remnants. Several factors contribute to postprandial lipid metabolism, including dietary, physiological, pathological and genetic factors. The presence of coronary heart disease, type 2 diabetes, insulin resistance and obesity is associated with higher postprandial TG levels compared with healthy conditions; this association is present also in subjects with normal fasting TG levels. Increasing evidence indicates that impaired metabolism of postprandial lipoproteins contributes to the pathogenesis of coronary artery disease, suggesting that lifestyle modifications as well as pharmacological approaches aimed at reducing postprandial TG levels might help to decrease the cardiovascular risk. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis , Ospedale Bassini, Cinisello Balsamo , Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20140502 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Hypolipidemic Agents) SB - IM MH - Cardiovascular Diseases/*etiology/prevention & control MH - Humans MH - Hyperlipoproteinemias/*complications/drug therapy/physiopathology MH - Hypertriglyceridemia/*complications/drug therapy/physiopathology MH - Hypolipidemic Agents/therapeutic use MH - Life Style MH - Lipid Metabolism MH - Postprandial Period/*physiology MH - Risk Factors OTO - NOTNLM OT - Chylomicron OT - Postprandial lipemia OT - Remnants OT - VLDL EDAT- 2014/03/29 06:00 MHDA- 2015/06/02 06:00 CRDT- 2014/03/29 06:00 PHST- 2014/03/29 06:00 [entrez] PHST- 2014/03/29 06:00 [pubmed] PHST- 2015/06/02 06:00 [medline] AID - 10.1185/03007995.2014.909394 [doi] PST - ppublish SO - Curr Med Res Opin. 2014 Aug;30(8):1489-503. doi: 10.1185/03007995.2014.909394. Epub 2014 May 2. PMID- 24969582 OWN - NLM STAT- MEDLINE DCOM- 20151001 LR - 20181202 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 37 IP - 8 DP - 2014 Aug TI - Statins and the risk of diabetes: evidence from a large population-based cohort study. PG - 2225-32 LID - 10.2337/dc13-2215 [doi] AB - OBJECTIVE: To investigate the relationship between adherence with statin therapy and the risk of developing diabetes. RESEARCH DESIGN AND METHODS: The cohort comprised 115,709 residents of the Italian Lombardy region who were newly treated with statins during 2003 and 2004. Patients were followed from the index prescription until 2010. During this period, patients who began therapy with an antidiabetic agent or were hospitalized for a main diagnosis of type 2 diabetes were identified (outcome). Adherence was measured by the proportion of days covered (PDC) with statins (exposure). A proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% CIs for the exposure-outcome association, after adjusting for several covariates. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: During follow-up, 11,154 cohort members experienced the outcome. Compared with patients with very-low adherence (PDC <25%), those with low (26-50%), intermediate (51-75%), and high (>/=75%) adherence to statin therapy had HRs (95% CIs) of 1.12 (1.06-1.18), 1.22 (1.14-1.27), and 1.32 (1.26-1.39), respectively. CONCLUSIONS: In a real-world setting, the risk of new-onset diabetes rises as adherence with statin therapy increases. Benefits of statins in reducing cardiovascular events clearly overwhelm the diabetes risk. CI - (c) 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy giovanni.corrao@unimib.it. FAU - Ibrahim, Buthaina AU - Ibrahim B AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Nicotra, Federica AU - Nicotra F AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Soranna, Davide AU - Soranna D AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Region Lombardia, Milan, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, ItalyIRCCS Multimedica, Sesto San Giovanni, Milan, Italy. FAU - Tragni, Elena AU - Tragni E AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy. FAU - Casula, Manuela AU - Casula M AD - Department of Pharmacological and Biomolecular Sciences, Centre of Epidemiology and Preventive Pharmacology (SEFAP), University of Milano, Milan, Italy. FAU - Grassi, Guido AU - Grassi G AD - IRCCS Multimedica, Sesto San Giovanni, Milan, ItalyDepartment of Health Science, University of Milano-Bicocca, Milan, Italy. FAU - Mancia, Giuseppe AU - Mancia G AD - Department of Health Science, University of Milano-Bicocca, Milan, ItalyIRCCS Istituto Auxologico Italiano, Milan, Italy. LA - eng PT - Journal Article DEP - 20140626 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cardiovascular Diseases/epidemiology/prevention & control MH - Cohort Studies MH - Diabetes Mellitus, Type 2/*epidemiology/*etiology MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypercholesterolemia/*drug therapy/*epidemiology MH - Incidence MH - Male MH - Medication Adherence/*statistics & numerical data MH - Middle Aged MH - Proportional Hazards Models MH - Retrospective Studies MH - Risk Factors EDAT- 2014/06/28 06:00 MHDA- 2015/10/02 06:00 CRDT- 2014/06/28 06:00 PHST- 2014/06/28 06:00 [entrez] PHST- 2014/06/28 06:00 [pubmed] PHST- 2015/10/02 06:00 [medline] AID - dc13-2215 [pii] AID - 10.2337/dc13-2215 [doi] PST - ppublish SO - Diabetes Care. 2014 Aug;37(8):2225-32. doi: 10.2337/dc13-2215. Epub 2014 Jun 26. PMID- 24731657 OWN - NLM STAT- MEDLINE DCOM- 20151214 LR - 20181113 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 2 IP - 8 DP - 2014 Aug TI - The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. PG - 655-66 LID - 10.1016/S2213-8587(13)70191-8 [doi] LID - S2213-8587(13)70191-8 [pii] AB - Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Hegele, Robert A AU - Hegele RA AD - Department of Medicine, Western University, London, ON, Canada. Electronic address: hegele@robarts.ca. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA. FAU - Chapman, M John AU - Chapman MJ AD - Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitie-Salpetriere University Hospital, Paris, France. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Department of Diagnostic Sciences, Herlev Hospital, University of Copenhagen, Denmark. FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA AD - Department of Molecular Genetics, University Medical Center Groningen, University of Groningen, Netherlands. FAU - Averna, Maurizio AU - Averna M AD - Department of Internal Medicine, University of Palermo, Palermo, Italy. FAU - Boren, Jan AU - Boren J AD - Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden. FAU - Bruckert, Eric AU - Bruckert E AD - Department of Endocrinology and Metabolism, Endocrinology and Cardiovascular Disease Prevention, Hopital Pitie-Salpetriere, Paris, France. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Sciences, University of Milan and Multimedica IRCSS, Milan, Italy. FAU - Descamps, Olivier S AU - Descamps OS AD - Centre de Recherche Medicale, Lipid Clinic, Hopital de Jolimont, Haine Saint-Paul, Belgium. FAU - Hovingh, G Kees AU - Hovingh GK AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. FAU - Humphries, Steve E AU - Humphries SE AD - Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK. FAU - Kovanen, Petri T AU - Kovanen PT AD - Wihuri Research Institute, Helsinki, Finland. FAU - Masana, Luis AU - Masana L AD - Vascular Medicine and Metabolism Unit, Sant Joan University Hospital, Universitat Rovira & Virgili, IISPV, CIBERDEM, Reus, Spain. FAU - Pajukanta, Paivi AU - Pajukanta P AD - Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. FAU - Parhofer, Klaus G AU - Parhofer KG AD - Department of Endocrinology and Metabolism, University of Munich, Munich, Germany. FAU - Raal, Frederick J AU - Raal FJ AD - Division of Endocrinology and Metabolism, Director of the Carbohydrate and Lipid Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa. FAU - Ray, Kausik K AU - Ray KK AD - Cardiovascular Sciences Research Centre, St George's Hospital NHS Trust, London, UK. FAU - Santos, Raul D AU - Santos RD AD - Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. FAU - Stalenhoef, Anton F H AU - Stalenhoef AF AD - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands. FAU - Stroes, Erik AU - Stroes E AD - Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. FAU - Taskinen, Marja-Riitta AU - Taskinen MR AD - Cardiovascular Research Group, Heart and Lung Centre, Helsinki University Central Hospital and Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. FAU - Tybjaerg-Hansen, Anne AU - Tybjaerg-Hansen A AD - Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Watts, Gerald F AU - Watts GF AD - School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia. FAU - Wiklund, Olov AU - Wiklund O AD - Department of Cardiology, Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden. CN - European Atherosclerosis Society Consensus Panel LA - eng GR - MOP-79523/Canadian Institutes of Health Research/Canada GR - RG/08/008/25291/British Heart Foundation/United Kingdom GR - CTP-79853/Canadian Institutes of Health Research/Canada GR - P01 HL028481/HL/NHLBI NIH HHS/United States GR - MOP-13430/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20131223 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Biomarkers) RN - 0 (Triglycerides) SB - IM CIN - Lancet Diabetes Endocrinol. 2014 Nov;2(11):860. PMID: 25439459 CIN - Lancet Diabetes Endocrinol. 2014 Nov;2(11):860-1. PMID: 25439460 MH - Animals MH - Biomarkers/blood MH - Combined Modality Therapy MH - Genetic Predisposition to Disease MH - Health Promotion MH - Humans MH - Hypertriglyceridemia/diagnosis/*etiology/genetics/therapy MH - Life Style MH - *Multifactorial Inheritance MH - Practice Guidelines as Topic MH - Triglycerides/blood PMC - PMC4201123 MID - NIHMS606588 EDAT- 2014/04/16 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/04/16 06:00 PHST- 2014/04/16 06:00 [entrez] PHST- 2014/04/16 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S2213-8587(13)70191-8 [pii] AID - 10.1016/S2213-8587(13)70191-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2014 Aug;2(8):655-66. doi: 10.1016/S2213-8587(13)70191-8. Epub 2013 Dec 23. PMID- 24924410 OWN - NLM STAT- MEDLINE DCOM- 20150331 LR - 20161125 IS - 1879-3649 (Electronic) IS - 1537-1891 (Linking) VI - 62 IP - 2 DP - 2014 Aug TI - PCSK9 inhibition for the treatment of hypercholesterolemia: promises and emerging challenges. PG - 103-11 LID - 10.1016/j.vph.2014.05.011 [doi] LID - S1537-1891(14)00107-4 [pii] AB - Hypercholesterolemia, is a prominent risk factor for cardiovascular disease (CVD). Undestanding of the biochemical mechanisms that regulate the expression of the low density lipoproteins receptor (LDLR) and the hepatic clearance of LDL cholesterol (LDL-C) paved the way to the statin therapy as the gold standard for CVD prevention. The discovery of proteins that regulate - at a post-translational level - the activity of the LDLR has been a major breakthrough in developing new cholesterol-lowering drugs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key modulator of the LDLR degradation in the liver. Genetic studies confirmed that in humans PCSK9 mutations associate with hypercholesterolemia and hypocholesterolemia (gain-of-function or loss-of-function variants respectively). Moreover, PCSK9 is up-regulated by statin treatment and limits the efficacy of these agents. These findings led to the development of PCSK9 inhibitors. Anti-PCSK9 monoclonal antibodies showed encouraging results and are currently being evaluated in phase III clinical trials. The aim of this short review is to describe the new frontier of PCSK9 inhibition in the treatment of hypercholesterolemia. Emphasis here is given to critical emerging issues linked to PCSK9 physiology and pharmacology, which will require future investigation to definitely address the potential of anti-PCSK9 drugs in clinical practice. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Center for the Study of Atherosclerosis, Societa Italiana Studio Aterosclerosi, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Tibolla, Gianpaolo AU - Tibolla G AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; I.R.C.C.S. Multimedica, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; I.R.C.C.S. Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20140609 PL - United States TA - Vascul Pharmacol JT - Vascular pharmacology JID - 101130615 RN - 0 (Antibodies, Monoclonal) RN - 0 (Anticholesteremic Agents) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology/therapeutic use MH - Anticholesteremic Agents/*pharmacology/*therapeutic use MH - Clinical Trials as Topic MH - Humans MH - Hypercholesterolemia/drug therapy/metabolism MH - Proprotein Convertase 9 MH - Proprotein Convertases/*antagonists & inhibitors/metabolism MH - Serine Endopeptidases/metabolism OTO - NOTNLM OT - Hypercholesterolemia OT - LDL cholesterol OT - LDL receptor OT - Monoclonal antibodies OT - PCSK9 EDAT- 2014/06/14 06:00 MHDA- 2015/04/01 06:00 CRDT- 2014/06/14 06:00 PHST- 2014/05/30 00:00 [received] PHST- 2014/05/31 00:00 [accepted] PHST- 2014/06/14 06:00 [entrez] PHST- 2014/06/14 06:00 [pubmed] PHST- 2015/04/01 06:00 [medline] AID - S1537-1891(14)00107-4 [pii] AID - 10.1016/j.vph.2014.05.011 [doi] PST - ppublish SO - Vascul Pharmacol. 2014 Aug;62(2):103-11. doi: 10.1016/j.vph.2014.05.011. Epub 2014 Jun 9. PMID- 24908248 OWN - NLM STAT- MEDLINE DCOM- 20140904 LR - 20181113 IS - 1546-1718 (Electronic) IS - 1061-4036 (Linking) VI - 46 IP - 7 DP - 2014 Jul TI - Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. PG - 731-5 LID - 10.1038/ng.3004 [doi] AB - Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined = 8.3 x 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of high-grade glioma and replication data (1,644 cases and 7,736 controls). This region has previously been associated with mean leukocyte telomere length (LTL). We therefore examined the relationship between LTL and both this new risk locus and other previously established risk loci for glioma using data from a recent GWAS of LTL (n = 37,684 individuals). Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (P = 5.5 x 10(-20) and 4.4 x 10(-19), respectively). In contrast, risk-associated alleles near RTEL1 were inconsistently associated with LTL, suggesting the presence of distinct causal alleles. No other risk loci for glioma were associated with LTL. The identification of risk alleles for glioma near TERC and TERT that also associate with telomere length implicates telomerase in gliomagenesis. FAU - Walsh, Kyle M AU - Walsh KM AD - 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA. FAU - Codd, Veryan AU - Codd V AD - 1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. FAU - Smirnov, Ivan V AU - Smirnov IV AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Rice, Terri AU - Rice T AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Decker, Paul A AU - Decker PA AD - Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Hansen, Helen M AU - Hansen HM AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Kollmeyer, Thomas AU - Kollmeyer T AD - Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Kosel, Matthew L AU - Kosel ML AD - Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Molinaro, Annette M AU - Molinaro AM AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - McCoy, Lucie S AU - McCoy LS AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Bracci, Paige M AU - Bracci PM AD - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. FAU - Cabriga, Belinda S AU - Cabriga BS AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Pekmezci, Melike AU - Pekmezci M AD - Department of Pathology, University of California, San Francisco, San Francisco, California, USA. FAU - Zheng, Shichun AU - Zheng S AD - Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Wiemels, Joseph L AU - Wiemels JL AD - 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. [3] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA. FAU - Pico, Alexander R AU - Pico AR AD - 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Department of Bioinformatics, Gladstone Institutes, San Francisco, California, USA. FAU - Tihan, Tarik AU - Tihan T AD - Department of Pathology, University of California, San Francisco, San Francisco, California, USA. FAU - Berger, Mitchell S AU - Berger MS AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Chang, Susan M AU - Chang SM AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Prados, Michael D AU - Prados MD AD - Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. FAU - Lachance, Daniel H AU - Lachance DH AD - Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - O'Neill, Brian Patrick AU - O'Neill BP AD - Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Sicotte, Hugues AU - Sicotte H AD - Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Eckel-Passow, Jeanette E AU - Eckel-Passow JE AD - Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. CN - ENGAGE Consortium Telomere Group FAU - van der Harst, Pim AU - van der Harst P AD - 1] Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [2] Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Wiencke, John K AU - Wiencke JK AD - 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA. FAU - Samani, Nilesh J AU - Samani NJ AD - 1] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. FAU - Jenkins, Robert B AU - Jenkins RB AD - Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Wrensch, Margaret R AU - Wrensch MR AD - 1] Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA. LA - eng GR - R01 CA139020/CA/NCI NIH HHS/United States GR - HHSN261201000034C/PHS HHS/United States GR - R01CA126831/CA/NCI NIH HHS/United States GR - British Heart Foundation/United Kingdom GR - U58DP003862-01/DP/NCCDPHP CDC HHS/United States GR - P50 CA108961/CA/NCI NIH HHS/United States GR - RC1 NS068222/NS/NINDS NIH HHS/United States GR - RC1NS068222Z/NS/NINDS NIH HHS/United States GR - MR/K014536/1/Medical Research Council/United Kingdom GR - HHSN261201000035C/PHS HHS/United States GR - R01 CA126831/CA/NCI NIH HHS/United States GR - P50 CA097257/CA/NCI NIH HHS/United States GR - R25CA112355/CA/NCI NIH HHS/United States GR - P30 CA015083/CA/NCI NIH HHS/United States GR - UL1RR024131/RR/NCRR NIH HHS/United States GR - P50CA097257/CA/NCI NIH HHS/United States GR - P50CA108961/CA/NCI NIH HHS/United States GR - P30CA15083/CA/NCI NIH HHS/United States GR - R01CA139020/CA/NCI NIH HHS/United States GR - R01CA52689/CA/NCI NIH HHS/United States GR - HHSN261201000140C/PHS HHS/United States GR - UL1 TR000004/TR/NCATS NIH HHS/United States GR - R01 CA052689/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140608 PL - United States TA - Nat Genet JT - Nature genetics JID - 9216904 RN - 0 (telomerase RNA) RN - 63231-63-0 (RNA) RN - EC 2.7.7.49 (TERT protein, human) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Adult MH - Case-Control Studies MH - Genome-Wide Association Study MH - Genotype MH - Glioma/*genetics/pathology MH - Humans MH - Leukocytes/metabolism/pathology MH - Neoplasm Grading MH - Polymorphism, Single Nucleotide/*genetics MH - Prognosis MH - RNA/*genetics MH - Risk Factors MH - Telomerase/*genetics MH - Telomere/*genetics PMC - PMC4074274 MID - NIHMS595175 IR - Codd V FIR - Codd, Veryan IR - Nelson CP FIR - Nelson, Christopher P IR - Albrecht E FIR - Albrecht, Eva IR - Mangino M FIR - Mangino, Massimo IR - Deelen J FIR - Deelen, Joris IR - Buxton JL FIR - Buxton, Jessica L IR - Hottenga JJ FIR - Hottenga, Jouke Jan IR - Fischer K FIR - Fischer, Krista IR - Esko T FIR - Esko, Tonu IR - Surakka I FIR - Surakka, Ida IR - Broer L FIR - Broer, Linda IR - Nyholt DR FIR - Nyholt, Dale R IR - Leach IM FIR - Leach, Irene Mateo IR - Salo P FIR - Salo, Perttu IR - Hagg S FIR - Hagg, Sara IR - Matthews MK FIR - Matthews, Mary K IR - Palmen J FIR - Palmen, Jutta IR - Norata GD FIR - Norata, Giuseppe D IR - O'Reilly PF FIR - O'Reilly, Paul F IR - Saleheen D FIR - Saleheen, Danish IR - Amin N FIR - Amin, Najaf IR - Balmforth AJ FIR - Balmforth, Anthony J IR - Beekman M FIR - Beekman, Marian IR - de Boer RA FIR - de Boer, Rudolf A IR - Bohringer S FIR - Bohringer, Stefan IR - Braund PS FIR - Braund, Peter S IR - Burton PR FIR - Burton, Paul R IR - de Craen AJ FIR - de Craen, Anton J M IR - Denniff M FIR - Denniff, Matthew IR - Dong Y FIR - Dong, Yanbin IR - Douroudis K FIR - Douroudis, Konstantinos IR - Dubinina E FIR - Dubinina, Elena IR - Eriksson JG FIR - Eriksson, Johan G IR - Garlaschelli K FIR - Garlaschelli, Katia IR - Guo D FIR - Guo, Dehuang IR - Hartikainen AL FIR - Hartikainen, Anna-Liisa IR - Henders AK FIR - Henders, Anjali K IR - Houwing-Duistermaat JJ FIR - Houwing-Duistermaat, Jeanine J IR - Kananen L FIR - Kananen, Laura IR - Karssen LC FIR - Karssen, Lennart C IR - Kettunen J FIR - Kettunen, Johannes IR - Klopp N FIR - Klopp, Norman IR - Lagou V FIR - Lagou, Vasiliki IR - van Leeuwen EM FIR - van Leeuwen, Elisabeth M IR - Madden PA FIR - Madden, Pamela A IR - Magi R FIR - Magi, Reedik IR - Magnusson PK FIR - Magnusson, Patrik K E IR - Mannisto S FIR - Mannisto, Satu IR - McCarthy MI FIR - McCarthy, Mark I IR - Medland SE FIR - Medland, Sarah E IR - Mihailov E FIR - Mihailov, Evelin IR - Montgomery GW FIR - Montgomery, Grant W IR - Oostra BA FIR - Oostra, Ben A IR - Palotie A FIR - Palotie, Aarno IR - Peters A FIR - Peters, Annette IR - Pollard H FIR - Pollard, Helen IR - Pouta A FIR - Pouta, Anneli IR - Prokopenko I FIR - Prokopenko, Inga IR - Ripatti S FIR - Ripatti, Samuli IR - Salomaa V FIR - Salomaa, Veikko IR - Suchiman H FIR - Suchiman, H Eka D IR - Valdes AM FIR - Valdes, Ana M IR - Verweij N FIR - Verweij, Niek IR - Vinuela A FIR - Vinuela, Ana IR - Wang X FIR - Wang, Xiaoling IR - Wichmann HE FIR - Wichmann, H-Erich IR - Widen E FIR - Widen, Elisabeth IR - Willemsen G FIR - Willemsen, Gonneke IR - Wright MJ FIR - Wright, Margaret J IR - Xia K FIR - Xia, Kai IR - Xiao X FIR - Xiao, Xiangjun IR - van Veldhuisen DJ FIR - van Veldhuisen, Dirk J IR - Catapano AL FIR - Catapano, Alberico L IR - Tobin MD FIR - Tobin, Martin D IR - Hall AS FIR - Hall, Alistair S IR - Blakemore AI FIR - Blakemore, Alexandra I F IR - van Gilst WH FIR - van Gilst, Wiek H IR - Zhu H FIR - Zhu, Haidong IR - Erdmann J FIR - Erdmann, Jeanette IR - Reilly MP FIR - Reilly, Muredach P IR - Kathiresan S FIR - Kathiresan, Sekar IR - Schunkert H FIR - Schunkert, Heribert IR - Talmud PJ FIR - Talmud, Philippa J IR - Pedersen NL FIR - Pedersen, Nancy L IR - Perola M FIR - Perola, Markus IR - Ouwehand W FIR - Ouwehand, Willem IR - Kaprio J FIR - Kaprio, Jaakko IR - Martin NG FIR - Martin, Nicholas G IR - van Duijn CM FIR - van Duijn, Cornelia M IR - Hovatta I FIR - Hovatta, Iiris IR - Gieger C FIR - Gieger, Christian IR - Metspalu A FIR - Metspalu, Andres IR - Boomsma DI FIR - Boomsma, Dorret I IR - Jarvelin MR FIR - Jarvelin, Marjo-Riitta IR - Slagboom P FIR - Slagboom, P Eline IR - Thompson JR FIR - Thompson, John R IR - Spector TD FIR - Spector, Tim D IR - van der Harst P FIR - van der Harst, Pim IR - Samani NJ FIR - Samani, Nilesh J EDAT- 2014/06/09 06:00 MHDA- 2014/09/05 06:00 CRDT- 2014/06/09 06:00 PHST- 2013/11/04 00:00 [received] PHST- 2014/05/12 00:00 [accepted] PHST- 2014/06/09 06:00 [entrez] PHST- 2014/06/09 06:00 [pubmed] PHST- 2014/09/05 06:00 [medline] AID - ng.3004 [pii] AID - 10.1038/ng.3004 [doi] PST - ppublish SO - Nat Genet. 2014 Jul;46(7):731-5. doi: 10.1038/ng.3004. Epub 2014 Jun 8. PMID- 24787906 OWN - NLM STAT- MEDLINE DCOM- 20150130 LR - 20151119 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 24 IP - 7 DP - 2014 Jul TI - Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus. PG - 751-9 LID - 10.1016/j.numecd.2014.01.006 [doi] LID - S0939-4753(14)00037-4 [pii] AB - BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 +/- 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 +/- 0.08 vs. 0.68 +/- 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naive T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Ammirati, E AU - Ammirati E AD - San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Heart Transplantation Division, Ospedale Niguarda Ca' Granda, Milan, Italy. Electronic address: ammirati.enrico@hsr.it. FAU - Bozzolo, E P AU - Bozzolo EP AD - The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: bozzolo.enrica@hsr.it. FAU - Contri, R AU - Contri R AD - San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: rachele.contri@gmail.com. FAU - Baragetti, A AU - Baragetti A AD - Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. Electronic address: andrea.baragetti@unimi.it. FAU - Palini, A G AU - Palini AG AD - San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Flow Cytometry Resource, Advanced Cytometry Technical Applications Laboratory, Milan, Italy; Nestle Institute of Health Science, Flow Cytometry, EPFL Innovation Park, 1015 Lausanne, Switzerland. Electronic address: palini.alessio@hsr.it. FAU - Cianflone, D AU - Cianflone D AD - San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: cianflone.domenico@hsr.it. FAU - Banfi, M AU - Banfi M AD - San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: banfi.michela@hsr.it. FAU - Uboldi, P AU - Uboldi P AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. Electronic address: Patrizia.Uboldi@unimi.it. FAU - Bottoni, G AU - Bottoni G AD - The Hull York Medical School, York, UK. Electronic address: grace.bottoni@gmail.com. FAU - Scotti, I AU - Scotti I AD - San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: Scotti.isabella@hsr.it. FAU - Pirillo, A AU - Pirillo A AD - Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy. Electronic address: Angela.Pirillo@guest.unimi.it. FAU - Grigore, L AU - Grigore L AD - Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy; The Multimedica IRCCS, Milan, Italy. Electronic address: Grigore.centroatero@gmail.com. FAU - Garlaschelli, K AU - Garlaschelli K AD - Center for The Study of Atherosclerosis, Italian Society for The Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello Balsamo, Milan, Italy. Electronic address: Garlaschelli.centroatero@gmail.com. FAU - Monaco, C AU - Monaco C AD - The University of Oxford, UK. Electronic address: claudia.monaco@kennedy.ox.ac.uk. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; The Multimedica IRCCS, Milan, Italy. Electronic address: Alberico.Catapano@unimi.it. FAU - Sabbadini, M G AU - Sabbadini MG AD - The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: sabbadini.mariagrazia@hsr.it. FAU - Manfredi, A A AU - Manfredi AA AD - The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy. Electronic address: manfredi.angelo@hsr.it. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: Danilo.Norata@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140201 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (ABCA1 protein, human) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (Biomarkers) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Immunologic Factors) RN - 4QWG6N8QKH (Hydroxychloroquine) SB - IM MH - ATP Binding Cassette Transporter 1/blood MH - Adult MH - Biomarkers/blood MH - Blood Pressure/drug effects MH - Body Mass Index MH - CD4-Positive T-Lymphocytes/metabolism MH - Cardiovascular Diseases/*blood/drug therapy MH - Carotid Artery, Common/drug effects/*physiopathology MH - *Carotid Intima-Media Thickness MH - Case-Control Studies MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Female MH - Humans MH - Hydroxychloroquine/therapeutic use MH - Immunologic Factors/*metabolism MH - Logistic Models MH - Lupus Erythematosus, Systemic/*blood/drug therapy MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Risk Factors OTO - NOTNLM OT - Atherosclerosis OT - CCR5 OT - Cardiovascular risk factors OT - Carotid intima-media thickness OT - HLA-DR OT - Hydroxychloroquine OT - Memory effector T cells OT - Systemic lupus erythematosus EDAT- 2014/05/03 06:00 MHDA- 2015/01/31 06:00 CRDT- 2014/05/03 06:00 PHST- 2013/07/12 00:00 [received] PHST- 2013/11/26 00:00 [revised] PHST- 2014/01/11 00:00 [accepted] PHST- 2014/05/03 06:00 [entrez] PHST- 2014/05/03 06:00 [pubmed] PHST- 2015/01/31 06:00 [medline] AID - S0939-4753(14)00037-4 [pii] AID - 10.1016/j.numecd.2014.01.006 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2014 Jul;24(7):751-9. doi: 10.1016/j.numecd.2014.01.006. Epub 2014 Feb 1. PMID- 24747112 OWN - NLM STAT- MEDLINE DCOM- 20150112 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 234 IP - 2 DP - 2014 Jun TI - Statins and periodontal inflammation: a pleiotropic effect of statins or a pleiotropic effect of LDL-cholesterol lowering? PG - 381-2 LID - 10.1016/j.atherosclerosis.2014.03.017 [doi] LID - S0021-9150(14)00166-X [pii] FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; Center for The Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen's Mary University, London, UK. Electronic address: Danilo.Norata@unimi.it. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: Alberico.Catapano@unimi.it. LA - eng PT - Journal Article PT - Comment DEP - 20140326 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Heptanoic Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Pyrroles) SB - IM CON - J Am Coll Cardiol. 2013 Dec 24;62(25):2382-91. PMID: 24070911 MH - Female MH - Heptanoic Acids/*administration & dosage MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage MH - Male MH - Periodontal Diseases/*diagnosis/*drug therapy MH - Pyrroles/*administration & dosage OTO - NOTNLM OT - LDL OT - Statin OT - periodontal inflammation OT - pleiotropic effects EDAT- 2014/04/22 06:00 MHDA- 2015/01/13 06:00 CRDT- 2014/04/22 06:00 PHST- 2014/03/14 00:00 [received] PHST- 2014/03/19 00:00 [accepted] PHST- 2014/04/22 06:00 [entrez] PHST- 2014/04/22 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] AID - S0021-9150(14)00166-X [pii] AID - 10.1016/j.atherosclerosis.2014.03.017 [doi] PST - ppublish SO - Atherosclerosis. 2014 Jun;234(2):381-2. doi: 10.1016/j.atherosclerosis.2014.03.017. Epub 2014 Mar 26. PMID- 25326928 OWN - NLM STAT- MEDLINE DCOM- 20160811 LR - 20141017 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 20 IP - 5 DP - 2014 May TI - Assessment and potential determinants of compliance and persistence to antiosteoporosis therapy in Italy. PG - e138-45 AB - OBJECTIVES: To analyze adherence to antiosteoporosis drugs (AODs) and to assess the influence of patient-related and drug-related factors. STUDY DESIGN: Observational, retrospective study. METHODS: Data on prescriptions for AODs from 2007 through 2008 were retrieved from administrative databases of 10 Italian local health units. Key measurements included compliance and persistence at 1 year. Multivariate regression analyses were performed to estimate adjusted risk ratios for compliance less than 80% and adjusted hazard ratios for no persistence. RESULTS: Of 40,004 new patients (89.9% women, mean age 69.8 years), 84.0% were treated with bisphosphonates and 74.6% of administration regimens were weekly. Overall, 75.1% of patients had suboptimal levels of compliance and 84.7% were not persistent; almost one-third had only 1 prescription. In regression analyses, younger age, change of drug, and concomitant corticosteroid therapy were significantly associated to compliance and persistence in both genders. In women, weekly and monthly regimens reduced the risk for poor compliance (sex-adjusted relative risks 0.729 [0.697-0.762], 0.846 [0.817-0.876], respectively) and no persistence (sex-adjusted hazard ratios 0.591 [0.541-0.646], 0.508 [0.461-0.560], respectively) compared with a daily regimen. CONCLUSIONS: In our study, 75% of subjects had discontinuous treatment and inadequate drug supply. Age and frequency of administration were strongly associated with adherence. Improvement is urgently needed, and occasional prescriptions represent the main target. FAU - Casula, Manuela AU - Casula M FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Piccinelli, Rossana AU - Piccinelli R FAU - Menditto, Enrica AU - Menditto E FAU - Manzoli, Lamberto AU - Manzoli L FAU - De Fendi, Luisa AU - De Fendi L FAU - Orlando, Valentina AU - Orlando V FAU - Flacco, Maria Elena AU - Flacco ME FAU - Gambera, Marco AU - Gambera M FAU - Filippi, Alessandro AU - Filippi A FAU - Tragni, Elena AU - Tragni E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Bone Density Conservation Agents) RN - 0 (Diphosphonates) SB - H MH - Adrenal Cortex Hormones/administration & dosage/therapeutic use MH - Age Factors MH - Aged MH - Bone Density Conservation Agents/administration & dosage/*therapeutic use MH - Diphosphonates/administration & dosage/*therapeutic use MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Humans MH - Italy MH - Male MH - Medication Adherence/*statistics & numerical data MH - Osteoporosis/*drug therapy MH - Risk Factors MH - Sex Factors EDAT- 2014/10/21 06:00 MHDA- 2016/08/12 06:00 CRDT- 2014/10/21 06:00 PHST- 2014/10/21 06:00 [entrez] PHST- 2014/10/21 06:00 [pubmed] PHST- 2016/08/12 06:00 [medline] PST - ppublish SO - Am J Manag Care. 2014 May;20(5):e138-45. PMID- 24681912 OWN - NLM STAT- MEDLINE DCOM- 20141211 LR - 20140414 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 234 IP - 1 DP - 2014 May TI - High-potency statins increase the risk of acute kidney injury: evidence from a large population-based study. PG - 224-9 LID - 10.1016/j.atherosclerosis.2014.02.022 [doi] LID - S0021-9150(14)00120-8 [pii] AB - OBJECTIVE: To assess the association between acute kidney injury and exposure to either high-potency statins or low-potency statins. DESIGN: A population-based, nested case-control study was performed on a cohort of 316,449 patients from Lombardy (Italy) newly treated with statins between 2007 and 2010 aged 40 years or older. 458 patients experienced acute kidney injury within six months after initial statin prescription. Up to four controls were randomly selected for each case. Logistic regression was used to model the outcome risk associated with high-potency contrasted with low-potency statins dispensed at starting therapy, and during follow-up. RESULTS: Patients at whom high-potency statins were initially dispensed were more likely to be hospitalized for acute kidney injury within six months after starting treatment than those on low-potency statins (adjusted OR 1.54, 95% confidence interval 1.25-1.91). Patients receiving high-potency statins within three weeks before the outcome onset had a significant increased risk respect to those who did not receive statins during the same time-window (adjusted OR 1.45, 95% confidence interval 1.04-2.03). When follow-up was extended from 6 months to 12 months the difference was not significant anymore (adjusted OR 1.17, 95% confidence interval 0.89-1.54). CONCLUSIONS: Use of high-potency statins is associated with an increased risk of acute kidney injury compared with low-potency statins in the first 6 months after starting therapy. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Corrao, Giovanni AU - Corrao G AD - Division of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. FAU - Soranna, Davide AU - Soranna D AD - Division of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy. FAU - Casula, Manuela AU - Casula M AD - Centre of Epidemiology and Preventive Pharmacology (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milano, Milan, Italy. FAU - Merlino, Luca AU - Merlino L AD - Operative Unit of Territorial Health Services, Region Lombardia, Milan, Italy. FAU - Porcellini, Maria Gabriella AU - Porcellini MG AD - Division of Paediatric Nephrology, Paediatric Hospital "Regina Margherita", Turin, Italy. FAU - Catapano, Alberico L AU - Catapano AL AD - Centre of Epidemiology and Preventive Pharmacology (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milano, Milan, Italy; IRCSS Multimedica, Milan, Italy. LA - eng PT - Journal Article DEP - 20140315 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Acute Kidney Injury/*chemically induced/*epidemiology MH - Aged MH - Case-Control Studies MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Male MH - Patient Admission/statistics & numerical data MH - Risk OTO - NOTNLM OT - Databases OT - Drug safety OT - High-potency OT - Kidney injury OT - Low-potency OT - Nested case-control study OT - Statins EDAT- 2014/04/01 06:00 MHDA- 2014/12/17 06:00 CRDT- 2014/04/01 06:00 PHST- 2013/12/02 00:00 [received] PHST- 2014/02/20 00:00 [revised] PHST- 2014/02/21 00:00 [accepted] PHST- 2014/04/01 06:00 [entrez] PHST- 2014/04/01 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] AID - S0021-9150(14)00120-8 [pii] AID - 10.1016/j.atherosclerosis.2014.02.022 [doi] PST - ppublish SO - Atherosclerosis. 2014 May;234(1):224-9. doi: 10.1016/j.atherosclerosis.2014.02.022. Epub 2014 Mar 15. PMID- 24462365 OWN - NLM STAT- MEDLINE DCOM- 20141217 LR - 20161125 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 24 IP - 5 DP - 2014 May TI - Pentraxin 3 (PTX3) plasma levels and carotid intima media thickness progression in the general population. PG - 518-23 LID - 10.1016/j.numecd.2013.10.030 [doi] LID - S0939-4753(13)00293-7 [pii] AB - BACKGROUND AND AIM: Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and, like C-reactive protein, is independently associated with the risk of developing vascular events. Aim of this study was to investigate, in two large population-based surveys, the Bruneck Study and the PLIC Study, whether PTX3 plasma levels predict the progression of common carotid artery intima-media thickness (CCA-IMT), a surrogate marker of atherosclerosis, in the general population during 5 or 6 years of follow-up. RESULTS: In the Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT either in the carotid artery or in the femoral artery. This finding was confirmed in the PLIC Study where subjects within the highest tertile of PTX3 did not show an increased progression of CCA-IMT. PTX3 plasma levels were also not associated with the fastest maximum IMT progression. In summary, in more than 2400 subjects from the general population, PTX3 plasma level is neither an independent predictor of progression of subclinical atherosclerosis in different arterial territories, including carotid and femoral arteries nor of incident cardiovascular events. CONCLUSION: These findings support the relevance of investigating the predictive value of PTX3 plasma levels only in specific settings, like overt CVD, heart failure or acute myocardial infarction. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Baragetti, A AU - Baragetti A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. FAU - Knoflach, M AU - Knoflach M AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Cuccovillo, I AU - Cuccovillo I AD - Department of Inflammation and Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. FAU - Grigore, L AU - Grigore L AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Casula, M AU - Casula M AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy. FAU - Garlaschelli, K AU - Garlaschelli K AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Mantovani, A AU - Mantovani A AD - Department of Inflammation and Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; Department of Translational Medicine, University of Milan, Milan, Italy. FAU - Wick, G AU - Wick G AD - Laboratory of Autoimmunity, Biocenter, Innsbruck, Austria. FAU - Kiechl, S AU - Kiechl S AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Willeit, J AU - Willeit J AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Bottazzi, B AU - Bottazzi B AD - Department of Inflammation and Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy; IRCCS Multimedica, Milan, Italy. Electronic address: alberico.catapano@unimi.it. FAU - Norata, G D AU - Norata GD AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Italy; The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, UK. Electronic address: danilo.norata@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131204 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Biomarkers) RN - 0 (Serum Amyloid P-Component) RN - 148591-49-5 (PTX3 protein) RN - 9007-41-4 (C-Reactive Protein) SB - IM CIN - Nutr Metab Cardiovasc Dis. 2014 Dec;24(12):e38-9. PMID: 25304608 MH - Aged MH - Aged, 80 and over MH - Animals MH - Biomarkers/*blood MH - C-Reactive Protein/*metabolism MH - Cardiovascular Diseases/blood/diagnostic imaging MH - Carotid Artery, Common/diagnostic imaging MH - *Carotid Intima-Media Thickness MH - Disease Progression MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Prospective Studies MH - Serum Amyloid P-Component/*metabolism OTO - NOTNLM OT - Bruneck Study OT - Inflammation OT - PLIC Study OT - PTX3 EDAT- 2014/01/28 06:00 MHDA- 2014/12/18 06:00 CRDT- 2014/01/28 06:00 PHST- 2013/07/10 00:00 [received] PHST- 2013/10/11 00:00 [revised] PHST- 2013/10/22 00:00 [accepted] PHST- 2014/01/28 06:00 [entrez] PHST- 2014/01/28 06:00 [pubmed] PHST- 2014/12/18 06:00 [medline] AID - S0939-4753(13)00293-7 [pii] AID - 10.1016/j.numecd.2013.10.030 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2014 May;24(5):518-23. doi: 10.1016/j.numecd.2013.10.030. Epub 2013 Dec 4. PMID- 24530786 OWN - NLM STAT- MEDLINE DCOM- 20141211 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 233 IP - 2 DP - 2014 Apr TI - Comment to the position paper on global recommendations for the management of dyslipidemia developed by the International Atherosclerosis Society (IAS). PG - 508-9 LID - 10.1016/j.atherosclerosis.2013.12.050 [doi] LID - S0021-9150(14)00028-8 [pii] FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan, 20133 Milano, Italy. FAU - Chapman, M J AU - Chapman MJ AD - University of Milan, 20133 Milano, Italy. FAU - de Backer, Guy AU - de Backer G AD - University of Milan, 20133 Milano, Italy. FAU - Taskinen, Marja-Riitta AU - Taskinen MR AD - University of Milan, 20133 Milano, Italy. FAU - Reiner, Zeljko AU - Reiner Z AD - University of Milan, 20133 Milano, Italy. FAU - Wiklund, Olov AU - Wiklund O AD - University of Milan, 20133 Milano, Italy. LA - eng PT - Journal Article PT - Comment DEP - 20140121 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 SB - IM CON - Rev Esp Cardiol. 2011 Dec;64(12):1168.e1-1168.e60. PMID: 22115524 MH - Dyslipidemias/*therapy MH - Humans EDAT- 2014/02/18 06:00 MHDA- 2014/12/17 06:00 CRDT- 2014/02/18 06:00 PHST- 2013/12/20 00:00 [received] PHST- 2013/12/26 00:00 [accepted] PHST- 2014/02/18 06:00 [entrez] PHST- 2014/02/18 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] AID - S0021-9150(14)00028-8 [pii] AID - 10.1016/j.atherosclerosis.2013.12.050 [doi] PST - ppublish SO - Atherosclerosis. 2014 Apr;233(2):508-9. doi: 10.1016/j.atherosclerosis.2013.12.050. Epub 2014 Jan 21. PMID- 24639424 OWN - NLM STAT- MEDLINE DCOM- 20141216 LR - 20170922 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 35 IP - 15 DP - 2014 Apr TI - The ACC/AHA 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: the good the bad and the uncertain: a comparison with ESC/EAS guidelines for the management of dyslipidaemias 2011. PG - 960-8 LID - 10.1093/eurheartj/ehu107 [doi] AB - Atherosclerotic cardiovascular disease is the most important public health problem of our time in both Europe and the rest of the world, accounting for the greatest expenditure in most healthcare budgets. Achieving consistency of clinical care, incorporating new evidence and their synthesis into practical recommendations for clinicians is the task of various guideline committees throughout the world. Any change in a set of guidelines therefore can have far reaching consequences, particularly if they appear to be at variance with the existing guidelines. The present article discusses the recent American College of Cardiology (ACC)/American Heart Association (AHA) guidelines 2013 on the control of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults. When compared with the ESC/EAS guidelines on lipid modification in 2011, the ACC/AHA guidelines of 2013 differ markedly. Specifically, (i) the scope is limited to randomized trials only, which excludes a significant body of data and promotes essentially a statin centric approach only; (ii) the abolition of low-density lipoprotein cholesterol (LDL-C) targets in favour of specific statin regimens that produce a 30-50% reduction in LDL-C we believe will confuse many physicians and miss the opportunity for medication adherence and patient engagement in self-management; (iii) the absence of target LDL-C levels in very high-risk patients with high absolute risk or residual risk factors will discourage clinicians to consider the addition of lipid modification treatments and individualize patient care; (iv) a reduction in the threshold for treatment in primary prevention will result in a greater number of patients being prescribed statin therapy, which is potentially good in young patients with high life time risk, but will result in a very large number of older patients offered therapy; and (v) the mixed pool risk calculator used to asses CVD risk in the guidelines for primary prevention has not been fully evaluated. This article discusses the potential implications of adopting the ACC/AHA guidelines on patient care in Europe and beyond and concludes with the opinion that the ESC/EAS guidelines from 2011 seem to be the most wide ranging, pragmatic and appropriate choice for European countries. FAU - Ray, Kausik K AU - Ray KK AD - St Georges University of London, London, UK. FAU - Kastelein, John J P AU - Kastelein JJ FAU - Boekholdt, S Matthijs AU - Boekholdt SM FAU - Nicholls, Stephen J AU - Nicholls SJ FAU - Khaw, Kay-Tee AU - Khaw KT FAU - Ballantyne, Christie M AU - Ballantyne CM FAU - Catapano, Alberico L AU - Catapano AL FAU - Reiner, Zeljko AU - Reiner Z FAU - Luscher, Thomas F AU - Luscher TF LA - eng GR - G0401527/Medical Research Council/United Kingdom GR - G1000143/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article DEP - 20140317 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - American Heart Association MH - Atherosclerosis/*prevention & control MH - Cholesterol, LDL/blood MH - Dyslipidemias/*prevention & control MH - Europe MH - Evidence-Based Medicine MH - Global Health MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypercholesterolemia/prevention & control MH - Patient Selection MH - *Practice Guidelines as Topic MH - Primary Prevention/methods MH - Risk Assessment/methods MH - Risk Factors MH - Risk Reduction Behavior MH - Societies, Medical MH - United States EDAT- 2014/03/19 06:00 MHDA- 2014/12/17 06:00 CRDT- 2014/03/19 06:00 PHST- 2014/03/19 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] AID - ehu107 [pii] AID - 10.1093/eurheartj/ehu107 [doi] PST - ppublish SO - Eur Heart J. 2014 Apr;35(15):960-8. doi: 10.1093/eurheartj/ehu107. Epub 2014 Mar 17. PMID- 24570151 OWN - NLM STAT- MEDLINE DCOM- 20141203 LR - 20181113 IS - 1558-9307 (Electronic) IS - 0024-4201 (Linking) VI - 49 IP - 4 DP - 2014 Apr TI - 15-lipoxygenase-mediated modification of HDL3 impairs eNOS activation in human endothelial cells. PG - 317-26 LID - 10.1007/s11745-014-3888-5 [doi] AB - Caveolae are cholesterol and glycosphingolipids-enriched microdomains of plasma membranes. Caveolin-1 represents the major structural protein of caveolae, that also contain receptors and molecules involved in signal transduction pathways. Caveolae are particularly abundant in endothelial cells, where they play important physiological and pathological roles in regulating endothelial cell functions. Several molecules with relevant functions in endothelial cells are localized in caveolae, including endothelial nitric oxide synthase (eNOS), which regulates the production of nitric oxide, and scavenger receptor class B type I (SR-BI), which plays a key role in the induction of eNOS activity mediated by high density lipoproteins (HDL). HDL have several atheroprotective functions, including a positive effect on endothelial cells, as it is a potent agonist of eNOS through the interaction with SR-BI. However, the oxidative modification of HDL may impair their protective role. In the present study we evaluated the effect of 15-lipoxygenase-mediated modification of HDL3 on the expression and/or activity of some proteins localized in endothelial caveolae and involved in the nitric oxide generation pathway. We found that after modification, HDL3 failed to activate eNOS and to induce NO production, due to both a reduced ability to interact with its own receptor SR-BI and to a reduced expression of SR-BI in cells exposed to modified HDL. These findings suggest that modification of HDL may reduce its endothelial-protective role also by interfering with vasodilatory function of HDL. FAU - Cutuli, Lucia AU - Cutuli L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A FAU - Uboldi, Patrizia AU - Uboldi P FAU - Kuehn, Hartmut AU - Kuehn H FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140226 PL - United States TA - Lipids JT - Lipids JID - 0060450 RN - 0 (Cholesterol, HDL) RN - 0 (SCARB1 protein, human) RN - 0 (Scavenger Receptors, Class B) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) RN - EC 1.14.13.39 (NOS3 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Arachidonate 15-Lipoxygenase/*metabolism MH - Caveolae/*metabolism MH - Cell Membrane/metabolism MH - Cholesterol, HDL/chemistry/*metabolism MH - Endothelial Cells/metabolism MH - Enzyme Activation/genetics MH - Humans MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type III/*biosynthesis MH - Scavenger Receptors, Class B/metabolism MH - Signal Transduction/genetics MH - Vasodilation EDAT- 2014/02/27 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/02/27 06:00 PHST- 2013/09/13 00:00 [received] PHST- 2014/02/12 00:00 [accepted] PHST- 2014/02/27 06:00 [entrez] PHST- 2014/02/27 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - 10.1007/s11745-014-3888-5 [doi] PST - ppublish SO - Lipids. 2014 Apr;49(4):317-26. doi: 10.1007/s11745-014-3888-5. Epub 2014 Feb 26. PMID- 24468148 OWN - NLM STAT- MEDLINE DCOM- 20140929 LR - 20140128 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 232 IP - 2 DP - 2014 Feb TI - Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. PG - 346-60 LID - 10.1016/j.atherosclerosis.2013.11.043 [doi] LID - S0021-9150(13)00694-1 [pii] AB - OBJECTIVE: This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. METHODS AND RESULTS: Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. CONCLUSION: Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols. CI - Copyright (c) 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved. FAU - Gylling, Helena AU - Gylling H AD - Department of Medicine, Division of Internal Medicine, University of Helsinki, Biomedicum Helsinki, Finland. Electronic address: Helena.Gylling@hus.fi. FAU - Plat, Jogchum AU - Plat J AD - Department of Human Biology, Maastricht University, The Netherlands. Electronic address: j.plat@maastrichtuniversity.nl. FAU - Turley, Stephen AU - Turley S AD - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, USA. Electronic address: Stephen.Turley@UTSouthwestern.edu. FAU - Ginsberg, Henry N AU - Ginsberg HN AD - Irving Institute for Clinical and Translational Research, Columbia University, New York, USA. Electronic address: hng1@columbia.edu. FAU - Ellegard, Lars AU - Ellegard L AD - Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Sweden. Electronic address: lasse.ellegard@nutrition.gu.se. FAU - Jessup, Wendy AU - Jessup W AD - ANZAC Research Institute, Concord Hospital, Sydney, Australia. Electronic address: wendy.jessup@gmail.com. FAU - Jones, Peter J AU - Jones PJ AD - Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Canada. Electronic address: Peter.Jones@umanitoba.ca. FAU - Lutjohann, Dieter AU - Lutjohann D AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Germany. Electronic address: Dieter.Luetjohann@ukb.uni-bonn.de. FAU - Maerz, Winfried AU - Maerz W AD - Synlab Academy, Synlab LLC, Mannheim Center of Laboratory Diagnostics, Heidelberg, Germany; Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, University of Heidelberg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. Electronic address: Winfried.Maerz@synlab.com. FAU - Masana, Luis AU - Masana L AD - Vascular Medicine and Metabolism Unit, University Hospital Sant Joan, IISPV, CIBERDEM, Rovira and Virgili University, Reus, Spain. Electronic address: luis.masana@urv.cat. FAU - Silbernagel, Gunther AU - Silbernagel G AD - Department of Angiology, Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland. Electronic address: guenther.silbernagel@yahoo.com. FAU - Staels, Bart AU - Staels B AD - Faculty of Pharmacy, University of Lille 2, Lille, France. Electronic address: Bart.Staels@pasteur-lille.fr. FAU - Boren, Jan AU - Boren J AD - Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR), University of Gothenburg, Sweden. Electronic address: Jan.Boren@wlab.gu.se. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; Multimedica IRCSS Milano, Italy. Electronic address: alberico.catapano@unimi.it. FAU - De Backer, Guy AU - De Backer G AD - Department of Public Health, University Hospital Ghent, Ghent, Belgium. Electronic address: guy.debacker@ugent.be. FAU - Deanfield, John AU - Deanfield J AD - National Centre for Cardiovascular Prevention and Outcomes, University College London, UK. Electronic address: john.deanfield@gmail.com. FAU - Descamps, Olivier S AU - Descamps OS AD - Lipid Clinic, Hopital de Jolimont, Haine-Saint-Paul, Belgium. Electronic address: olivierdescamps@hotmail.com. FAU - Kovanen, Petri T AU - Kovanen PT AD - Wihuri Research Institute, Helsinki, Finland. Electronic address: Petri.Kovanen@wri.fi. FAU - Riccardi, Gabriele AU - Riccardi G AD - Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. Electronic address: riccardi@unina.it. FAU - Tokgozoglu, Lale AU - Tokgozoglu L AD - Department of Cardiology, Hacettepe University, Ankara, Turkey. Electronic address: lalet@hacettepe.edu.tr. FAU - Chapman, M John AU - Chapman MJ AD - University of Pierre and Marie Curie, Paris, France; Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitie-Salpetriere University Hospital, Paris, France. Electronic address: john.chapman@upmc.fr. CN - European Atherosclerosis Society Consensus Panel on Phytosterols LA - eng GR - R01HL09610/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20131123 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - 0 (Lipids) RN - 0 (Phytosterols) RN - 0 (Sitosterols) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) SB - IM CIN - Atherosclerosis. 2014 Apr;233(2):357-8. PMID: 24530762 MH - Animals MH - Anticholesteremic Agents/*therapeutic use MH - Cardiovascular Diseases/blood/prevention & control/*therapy MH - Cholesterol/blood/metabolism MH - Cholesterol, LDL/blood MH - Dyslipidemias/*therapy MH - Humans MH - Inflammation/drug therapy MH - Lipids/blood MH - Phytosterols/*therapeutic use MH - Sitosterols/*therapeutic use MH - Triglycerides/blood OTO - NOTNLM OT - Cardiovascular risk OT - Functional foods with added plant sterols and plant stanols OT - Hypercholesterolaemia OT - Intestinal cholesterol absorption OT - Phytosterols OT - Safety EDAT- 2014/01/29 06:00 MHDA- 2014/09/30 06:00 CRDT- 2014/01/29 06:00 PHST- 2013/11/11 00:00 [received] PHST- 2013/11/11 00:00 [accepted] PHST- 2014/01/29 06:00 [entrez] PHST- 2014/01/29 06:00 [pubmed] PHST- 2014/09/30 06:00 [medline] AID - S0021-9150(13)00694-1 [pii] AID - 10.1016/j.atherosclerosis.2013.11.043 [doi] PST - ppublish SO - Atherosclerosis. 2014 Feb;232(2):346-60. doi: 10.1016/j.atherosclerosis.2013.11.043. Epub 2013 Nov 23. PMID- 24160703 OWN - NLM STAT- MEDLINE DCOM- 20140902 LR - 20161125 IS - 1545-4304 (Electronic) IS - 0362-1642 (Linking) VI - 54 DP - 2014 TI - Targeting PCSK9 for hypercholesterolemia. PG - 273-93 LID - 10.1146/annurev-pharmtox-011613-140025 [doi] AB - Dyslipidemias are a predominant risk factor for cardiovascular disease. Biological and genetic research has led to the identification of several genes and proteins that may be pharmacologically targeted to improve lipoprotein profiles and possibly cardiovascular outcomes in patients with dyslipidemia. The observation that proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the levels of circulating low-density lipoprotein C (LDL-C) by enhancing the degradation of the hepatic low-density lipoprotein receptor (LDLR) prompted the search for drugs that inhibit PCSK9 activity. Several approaches to inhibiting PCSK9 activity have been proposed; these involve inhibitory antibodies, small molecules, and gene silencing. To date, the most promising and advanced approach relates to monoclonal antibodies, which can decrease LDL cholesterol by 65-70%, even as an add-on therapy to a maximal dose of a statin. Phase III studies and large, event-driven clinical trials are ongoing and will fully address the viability and role of these drugs in clinical practice. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy; email: danilo.norata@unimi.it , gianpaolo.tibolla@unimi.it , alberico.catapano@unimi.it. FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20131016 PL - United States TA - Annu Rev Pharmacol Toxicol JT - Annual review of pharmacology and toxicology JID - 7607088 RN - 0 (Antibodies, Monoclonal) RN - 0 (Cholesterol, LDL) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Animals MH - Antibodies, Monoclonal/administration & dosage MH - Cholesterol, LDL/blood MH - Disease Models, Animal MH - Gene Expression Regulation MH - Hypercholesterolemia/*therapy MH - *Molecular Targeted Therapy MH - Proprotein Convertase 9 MH - Proprotein Convertases/*antagonists & inhibitors/blood/genetics MH - Randomized Controlled Trials as Topic MH - Serine Endopeptidases/blood/genetics EDAT- 2013/10/29 06:00 MHDA- 2014/09/03 06:00 CRDT- 2013/10/29 06:00 PHST- 2013/10/29 06:00 [entrez] PHST- 2013/10/29 06:00 [pubmed] PHST- 2014/09/03 06:00 [medline] AID - 10.1146/annurev-pharmtox-011613-140025 [doi] PST - ppublish SO - Annu Rev Pharmacol Toxicol. 2014;54:273-93. doi: 10.1146/annurev-pharmtox-011613-140025. Epub 2013 Oct 16. PMID- 24503730 OWN - NLM STAT- MEDLINE DCOM- 20140404 LR - 20140207 IS - 1827-6806 (Print) IS - 1827-6806 (Linking) VI - 15 IP - 1 DP - 2014 Jan TI - [The new 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk: comparison with the ESC/EAS recommendations for the management of dyslipidemias]. PG - 19-20 LID - 10.1714/1394.15514 [doi] FAU - Catapano, Alberico L AU - Catapano AL FAU - Averna, Maurizio AU - Averna M FAU - Faggiano, Pompilio AU - Faggiano P FAU - Novo, Salvatore AU - Novo S LA - ita PT - Comparative Study PT - Editorial TT - Nuove linee guida americane 2013 ACC/AHA sul trattamento del colesterolo plasmatico per ridurre il rischio cardiovascolare aterosclerotico: confronto con le raccomandazioni ESC/EAS per la gestione delle dislipidemie. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - American Heart Association MH - Atherosclerosis/etiology/*prevention & control MH - Cardiovascular Diseases/etiology/*prevention & control MH - Cholesterol/blood MH - Dyslipidemias/complications/*therapy MH - Europe MH - Humans MH - *Practice Guidelines as Topic MH - Societies, Medical MH - United States EDAT- 2014/02/08 06:00 MHDA- 2014/04/05 06:00 CRDT- 2014/02/08 06:00 PHST- 2014/02/08 06:00 [entrez] PHST- 2014/02/08 06:00 [pubmed] PHST- 2014/04/05 06:00 [medline] AID - 10.1714/1394.15514 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2014 Jan;15(1):19-20. doi: 10.1714/1394.15514. PMID- 23774666 OWN - NLM STAT- MEDLINE DCOM- 20141013 LR - 20140124 IS - 1662-8128 (Electronic) IS - 1662-811X (Linking) VI - 6 IP - 1 DP - 2014 TI - The CD1d-natural killer T cell axis in atherosclerosis. PG - 3-12 LID - 10.1159/000351034 [doi] AB - A key role for 'lipid-sensing' CD1-restricted natural killer T (NKT) cells in the pathogenesis of atherosclerosis has been suggested. However, the biology of NKT cells remains poorly characterized, as in different experimental settings their activation was reported to both stimulate and suppress innate and adaptive immune responses. Most of the data from experimental models suggest that NKT cells are proatherogenic; however, it is debated whether the increase in atherosclerosis observed following NKT cell stimulation is a consequence of the inability to induce functional NKT cells rather than the proatherogenic nature of NKT cells. CD1d-expressing antigen-presenting cells and NKT cells were detected in mouse and human atherosclerotic lesions. Furthermore, several lysophospholipids and glycosphingolipids, known to accumulate in atherosclerotic plaques, are antigenic for human NKT cell clones. Lipid transfer proteins, such as apolipoprotein E and microsomal triglyceride transfer protein, are central to NKT cell responses. All these data suggest a profound relation between lipid metabolism, CD1d-NKT cell axis activation and atherosclerosis. In this review, we summarize the advances and gaps in our knowledge of NKT cell biology in the context of atherosclerosis as well as the possibility of influencing NKT cell polarization toward an atheroprotective phenotype. CI - Copyright (c) 2013 S. Karger AG, Basel. FAU - Bondarenko, Sergey AU - Bondarenko S AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130613 PL - Switzerland TA - J Innate Immun JT - Journal of innate immunity JID - 101469471 RN - 0 (Antigens, CD1) RN - 0 (Carrier Proteins) RN - 0 (lipid transfer protein) SB - IM MH - Animals MH - Antigen-Presenting Cells/*immunology MH - Antigens, CD1/metabolism MH - Atherosclerosis/*immunology MH - Carrier Proteins/metabolism MH - Humans MH - Immunomodulation MH - Lipid Metabolism MH - Lymphocyte Activation MH - Mice MH - Natural Killer T-Cells/*immunology EDAT- 2013/06/19 06:00 MHDA- 2014/10/14 06:00 CRDT- 2013/06/19 06:00 PHST- 2012/09/20 00:00 [received] PHST- 2013/03/29 00:00 [accepted] PHST- 2013/06/19 06:00 [entrez] PHST- 2013/06/19 06:00 [pubmed] PHST- 2014/10/14 06:00 [medline] AID - 000351034 [pii] AID - 10.1159/000351034 [doi] PST - ppublish SO - J Innate Immun. 2014;6(1):3-12. doi: 10.1159/000351034. Epub 2013 Jun 13. PMID- 23806740 OWN - NLM STAT- MEDLINE DCOM- 20141020 LR - 20151119 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 24 IP - 1 DP - 2014 Jan TI - Lower incidence of macrovascular complications in patients on insulin glargine versus those on basal human insulins: a population-based cohort study in Italy. PG - 10-7 LID - 10.1016/j.numecd.2013.04.002 [doi] LID - S0939-4753(13)00090-2 [pii] AB - BACKGROUND AND AIM: The aim of this study was to compare the use of insulin glargine and intermediate/long-acting human insulin (HI) in relation to the incidence of complications in diabetic patients. METHODS AND RESULTS: A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients without macrovascular diseases and treated with either intermediate/long-acting HI or glargine were followed for 3-years; the incidence of diabetic (macrovascular, microvascular and metabolic) complications was ascertained by hospital discharge claims and estimated using Cox proportional hazard models. Propensity score (PS) matching was also used to adjust for significant differences in the baseline characteristics between the two groups. RESULTS: Overall, 1921 diabetic patients were included: 744 intermediate/long-acting HI and 1177 glargine users. During the 3-year follow-up, 209 (28.1%) incident events of any diabetic complication occurred in the intermediate/long-acting HI and 159 (13.5%) in the glargine group. After adjustment for covariates, glargine users had an HR (95% CI) of 0.57 (0.44-0.74) for any diabetic complication and HRs of 0.61 (0.44-0.84), 0.58 (0.33-1.04) and 0.35 (0.18-0.70) for macrovascular, microvascular and metabolic complications, respectively, compared to intermediate/long-acting HI users. PS analyses supported these findings. CONCLUSIONS: The use of glargine is associated with a lower risk of macrovascular complications compared with traditional basal insulins. However, limitations inherent to the study design including the short length of observation and the lack of data on metabolic control or diabetes duration, do not allow us to consider this association as a proof of causality. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Cammarota, S AU - Cammarota S AD - CIRFF, "Federico II" University of Naples, Italy. FAU - Bruzzese, D AU - Bruzzese D AD - Department of Preventive Medical Sciences, "Federico II" University of Naples, Italy. FAU - Catapano, A L AU - Catapano AL AD - SEFAP, Department of Pharmacological Sciences, University of Milan, Italy; Multimedica IRCCS, S.S. Giovanni, Italy. FAU - Citarella, A AU - Citarella A AD - CIRFF, "Federico II" University of Naples, Italy. FAU - De Luca, L AU - De Luca L AD - CIRFF, "Federico II" University of Naples, Italy. FAU - Manzoli, L AU - Manzoli L AD - Section of Hygiene, Epidemiology, Pharmacology and Legal Medicine, University of Chieti, and Regional Health Care Agency of Abruzzo, Italy. FAU - Masulli, M AU - Masulli M AD - Department of Clinical and Experimental Medicine, "Federico II" University of Naples, Italy. FAU - Menditto, E AU - Menditto E AD - CIRFF, "Federico II" University of Naples, Italy. FAU - Mezzetti, A AU - Mezzetti A AD - Clinical Research Centre, "G. D'Annunzio" University Foundation, Chieti, Italy. FAU - Riegler, S AU - Riegler S AD - CIRFF, "Federico II" University of Naples, Italy. FAU - Putignano, D AU - Putignano D AD - CIRFF, "Federico II" University of Naples, Italy. FAU - Tragni, E AU - Tragni E AD - SEFAP, Department of Pharmacological Sciences, University of Milan, Italy. FAU - Novellino, E AU - Novellino E AD - CIRFF, "Federico II" University of Naples, Italy. FAU - Riccardi, G AU - Riccardi G AD - Department of Clinical and Experimental Medicine, "Federico II" University of Naples, Italy. Electronic address: riccardi@unina.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130624 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Insulin, Long-Acting) RN - 0 (insulin, long-acting, human) RN - 2ZM8CX04RZ (Insulin Glargine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Diabetes Complications/*epidemiology/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Follow-Up Studies MH - Humans MH - Incidence MH - Insulin Glargine MH - Insulin, Long-Acting/*therapeutic use MH - Italy/epidemiology MH - Longitudinal Studies MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Retrospective Studies MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - Administrative data OT - Basal human insulins OT - Insulin glargine OT - Macrovascular complications OT - Propensity-score matching EDAT- 2013/06/29 06:00 MHDA- 2014/10/21 06:00 CRDT- 2013/06/29 06:00 PHST- 2012/10/04 00:00 [received] PHST- 2013/02/25 00:00 [revised] PHST- 2013/04/05 00:00 [accepted] PHST- 2013/06/29 06:00 [entrez] PHST- 2013/06/29 06:00 [pubmed] PHST- 2014/10/21 06:00 [medline] AID - S0939-4753(13)00090-2 [pii] AID - 10.1016/j.numecd.2013.04.002 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2014 Jan;24(1):10-7. doi: 10.1016/j.numecd.2013.04.002. Epub 2013 Jun 24. PMID- 23856442 OWN - NLM STAT- MEDLINE DCOM- 20140824 LR - 20131216 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 170 IP - 2 Suppl 1 DP - 2013 Dec 20 TI - Omega-3 polyunsaturated fatty acids in the treatment of hypertriglyceridaemia. PG - S16-20 LID - 10.1016/j.ijcard.2013.06.040 [doi] LID - S0167-5273(13)01094-2 [pii] AB - Hypertriglyceridaemia (HTG) is an independent risk factor for cardiovascular disease; high-risk patients with HTG, such as those with metabolic syndrome or diabetes, may benefit from hypolipidaemic therapies. Several lipid-lowering drugs act by reducing triglyceride (TG) levels, including fibrates, nicotinic acid and omega-3 fatty acids. The omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dose-dependently reduce plasma TG levels; the effect tends to be greater in patients with higher TG levels at baseline. Evidence from clinical trials suggests that EPA+DHA doses of >/= 2 g/day are required to achieve significant effects. The optimal TG-lowering doses of EPA+DHA are 3-4 g/day, with little evidence to support lipid-altering efficacy of doses of EPA and DHA <1g/day. Predicted changes in fasting serum TG levels at the recommended dietary intakes of EPA and/or DHA of 200-500 mg/day are -3.1% to -7.2%. Reductions of plasma TG levels at the optimal doses are from 25-35% up to 45% in the presence of severely elevated TG levels (>/= 500 mg/dl; >/= 5.65 mmol/l), along with a reduction in non-high-density lipoprotein-cholesterol (non-HDL-C) and an increase in HDL-C. This observation has also been confirmed in statin-treated patients. CI - (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; IRCCS MultiMedica, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL AD - IRCCS MultiMedica, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. Electronic address: alberico.catapano@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20130712 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Fatty Acids, Omega-3) RN - 0 (Triglycerides) SB - IM MH - Animals MH - Fatty Acids, Omega-3/*administration & dosage/metabolism MH - Humans MH - Hypertriglyceridemia/*blood/*diet therapy MH - Randomized Controlled Trials as Topic/methods MH - Treatment Outcome MH - Triglycerides/blood OTO - NOTNLM OT - Diabetes OT - Docosahexaenoic acid OT - Eicosapentaenoic acid OT - Hypertriglyceridaemia OT - Omega-3 fatty acids OT - Triglyceride EDAT- 2013/07/17 06:00 MHDA- 2014/08/26 06:00 CRDT- 2013/07/17 06:00 PHST- 2013/07/17 06:00 [entrez] PHST- 2013/07/17 06:00 [pubmed] PHST- 2014/08/26 06:00 [medline] AID - S0167-5273(13)01094-2 [pii] AID - 10.1016/j.ijcard.2013.06.040 [doi] PST - ppublish SO - Int J Cardiol. 2013 Dec 20;170(2 Suppl 1):S16-20. doi: 10.1016/j.ijcard.2013.06.040. Epub 2013 Jul 12. PMID- 23956253 OWN - NLM STAT- MEDLINE DCOM- 20140723 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 34 IP - 45 DP - 2013 Dec TI - Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. PG - 3478-90a LID - 10.1093/eurheartj/eht273 [doi] AB - AIMS: The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD). METHODS AND RESULTS: Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult >/=8 mmol/L(>/=310 mg/dL) or a child >/=6 mmol/L(>/=230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD. CONCLUSION: Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition. FAU - Nordestgaard, Borge G AU - Nordestgaard BG AD - Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2730 Herlev, Copenhagen, Denmark. FAU - Chapman, M John AU - Chapman MJ FAU - Humphries, Steve E AU - Humphries SE FAU - Ginsberg, Henry N AU - Ginsberg HN FAU - Masana, Luis AU - Masana L FAU - Descamps, Olivier S AU - Descamps OS FAU - Wiklund, Olov AU - Wiklund O FAU - Hegele, Robert A AU - Hegele RA FAU - Raal, Frederick J AU - Raal FJ FAU - Defesche, Joep C AU - Defesche JC FAU - Wiegman, Albert AU - Wiegman A FAU - Santos, Raul D AU - Santos RD FAU - Watts, Gerald F AU - Watts GF FAU - Parhofer, Klaus G AU - Parhofer KG FAU - Hovingh, G Kees AU - Hovingh GK FAU - Kovanen, Petri T AU - Kovanen PT FAU - Boileau, Catherine AU - Boileau C FAU - Averna, Maurizio AU - Averna M FAU - Boren, Jan AU - Boren J FAU - Bruckert, Eric AU - Bruckert E FAU - Catapano, Alberico L AU - Catapano AL FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA FAU - Pajukanta, Paivi AU - Pajukanta P FAU - Ray, Kausik AU - Ray K FAU - Stalenhoef, Anton F H AU - Stalenhoef AF FAU - Stroes, Erik AU - Stroes E FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Tybjaerg-Hansen, Anne AU - Tybjaerg-Hansen A CN - European Atherosclerosis Society Consensus Panel LA - eng GR - P01 HL028481/HL/NHLBI NIH HHS/United States GR - RG/08/008/25291/British Heart Foundation/United Kingdom PT - Consensus Development Conference PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130815 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Anticholesteremic Agents/therapeutic use MH - Atherosclerosis/diagnosis MH - Child MH - Child, Preschool MH - Cholesterol, LDL/blood MH - Coronary Disease/*prevention & control MH - Cost-Benefit Analysis MH - Delivery of Health Care MH - Early Diagnosis MH - Female MH - Forecasting MH - Heterozygote MH - Homozygote MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hyperlipoproteinemia Type II/*diagnosis/genetics/*therapy MH - Male MH - Middle Aged MH - Mutation/genetics MH - Pedigree MH - Risk Assessment MH - Treatment Outcome PMC - PMC3844152 OTO - NOTNLM OT - Atherosclerosis OT - Cardiovascular disease OT - Cholesterol OT - Coronary heart disease OT - Low-density lipoprotein EDAT- 2013/08/21 06:00 MHDA- 2014/07/24 06:00 CRDT- 2013/08/20 06:00 PHST- 2013/08/20 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2014/07/24 06:00 [medline] AID - eht273 [pii] AID - 10.1093/eurheartj/eht273 [doi] PST - ppublish SO - Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15. PMID- 24244557 OWN - NLM STAT- MEDLINE DCOM- 20140812 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 11 DP - 2013 TI - Lower rate of cardiovascular complications in patients on bolus insulin analogues: a retrospective population-based cohort study. PG - e79762 LID - 10.1371/journal.pone.0079762 [doi] AB - BACKGROUND: Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases. METHODS: A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients' characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups. RESULTS: A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58-0.92) for any diabetes-related complication and HRs of 0.73 (0.55-0.93) and 0.55 (0.32-0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications. CONCLUSIONS: Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use. FAU - Cammarota, Simona AU - Cammarota S AD - Center of Pharmacoeconomics and Drug Utilization (CIRFF), "Federico II" University of Naples, Naples, Italy. FAU - Falconio, Lucio Marcello AU - Falconio LM FAU - Bruzzese, Dario AU - Bruzzese D FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Casula, Manuela AU - Casula M FAU - Citarella, Anna AU - Citarella A FAU - De Luca, Luigi AU - De Luca L FAU - Flacco, Maria Elena AU - Flacco ME FAU - Manzoli, Lamberto AU - Manzoli L FAU - Masulli, Maria AU - Masulli M FAU - Menditto, Enrica AU - Menditto E FAU - Mezzetti, Andrea AU - Mezzetti A FAU - Riegler, Salvatore AU - Riegler S FAU - Novellino, Ettore AU - Novellino E FAU - Riccardi, Gabriele AU - Riccardi G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131107 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin, Regular, Human) RN - 0 (Insulin, Short-Acting) SB - IM MH - Aged MH - Aged, 80 and over MH - Cardiovascular Diseases/*drug therapy/etiology/metabolism/pathology MH - Diabetes Mellitus, Type 1/complications/*drug therapy/metabolism/pathology MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism/pathology MH - Female MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Insulin, Regular, Human/*therapeutic use MH - Insulin, Short-Acting/*therapeutic use MH - Male MH - Middle Aged MH - Proportional Hazards Models MH - Retrospective Studies PMC - PMC3820645 EDAT- 2013/11/19 06:00 MHDA- 2014/08/13 06:00 CRDT- 2013/11/19 06:00 PHST- 2013/07/12 00:00 [received] PHST- 2013/09/26 00:00 [accepted] PHST- 2013/11/19 06:00 [entrez] PHST- 2013/11/19 06:00 [pubmed] PHST- 2014/08/13 06:00 [medline] AID - 10.1371/journal.pone.0079762 [doi] AID - PONE-D-13-28917 [pii] PST - epublish SO - PLoS One. 2013 Nov 7;8(11):e79762. doi: 10.1371/journal.pone.0079762. eCollection 2013. PMID- 24147143 OWN - NLM STAT- MEDLINE DCOM- 20140605 LR - 20190226 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 10 DP - 2013 TI - Prevalence of the prescription of potentially interacting drugs. PG - e78827 LID - 10.1371/journal.pone.0078827 [doi] AB - The use of multiple medications is becoming more common, with a correspondingly increased risk of untoward effects and drug-related morbidity and mortality. We aimed at estimating the prevalence of prescription of relevant potentially interacting drugs and at evaluating possible predictors of potentially interacting drug exposure. We retrospectively analyzed data on prescriptions dispensed from January 2004 to August 2005 to individuals of two Italian regions with a population of almost 2.1 million individuals. We identified 27 pairs of potentially interacting drugs by examining clinical relevance, documentation, and volume of use in Italy. Subjects who received at least one prescription of both drugs were selected. Co-prescribing denotes "two prescriptions in the same day", and concomitant medication "the prescription of two drugs with overlapping coverage". A logistic regression analysis was conducted to examine the predictors of potential Drug-Drug Interaction (pDDIs). 957,553 subjects (45.3% of study population) were exposed to at least one of the drugs/classes of the 27 pairs. Overall, pDDIs occurred 2,465,819 times. The highest rates of concomitant prescription and of co-prescription were for ACE inhibitors+NSAIDs (6,253 and 4,621/100,000 plan participants). Considering concomitance, the male/female ratio was <1 in 17/27 pairs (from 0.31 for NSAIDs-ASA+SSRI to 0.74 for omeprazole+clopidogrel). The mean age was lowest for methotrexate pairs (+omeprazole, 59.9 years; +NSAIDs-ASA, 59.1 years) and highest for digoxin+verapamil (75.4 years). In 13/27 pairs, the mean ages were >/=70 years. On average, subjects involved in pDDIs received >/=10 drugs. The odds of exposure were more frequently higher for age >/=65 years, males, and those taking a large number of drugs. A substantial number of clinically important pDDIs were observed, particularly among warfarin users. Awareness of the most prevalent pDDIs could help practitioners in preventing concomitant use, resulting in a better quality of drug prescription and potentially avoiding unwanted side effects. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), University of Milan, Italy. FAU - Casula, Manuela AU - Casula M FAU - Pieri, Vasco AU - Pieri V FAU - Favato, Giampiero AU - Favato G FAU - Marcobelli, Alberico AU - Marcobelli A FAU - Trotta, Maria Giovanna AU - Trotta MG FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article DEP - 20131011 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM EIN - PLoS One.2013;8(11). doi:10.1371/annotation/01652378-8216-4387-9b89-a43429707cae MH - *Drug Interactions MH - Drug Prescriptions/*statistics & numerical data MH - Female MH - Humans MH - Male MH - Middle Aged MH - Prevalence PMC - PMC3795676 EDAT- 2013/10/23 06:00 MHDA- 2014/06/06 06:00 CRDT- 2013/10/23 06:00 PHST- 2013/01/14 00:00 [received] PHST- 2013/09/16 00:00 [accepted] PHST- 2013/10/23 06:00 [entrez] PHST- 2013/10/23 06:00 [pubmed] PHST- 2014/06/06 06:00 [medline] AID - 10.1371/journal.pone.0078827 [doi] AID - PONE-D-13-02407 [pii] PST - epublish SO - PLoS One. 2013 Oct 11;8(10):e78827. doi: 10.1371/journal.pone.0078827. eCollection 2013. PMID- 23623664 OWN - NLM STAT- MEDLINE DCOM- 20141218 LR - 20171116 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 168 IP - 3 DP - 2013 Oct 3 TI - Prevalence of classical CD14++/CD16- but not of intermediate CD14++/CD16+ monocytes in hypoalphalipoproteinemia. PG - 2886-9 LID - 10.1016/j.ijcard.2013.03.103 [doi] LID - S0167-5273(13)00534-2 [pii] FAU - Sala, Federica AU - Sala F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Cutuli, Lucia AU - Cutuli L FAU - Grigore, Liliana AU - Grigore L FAU - Pirillo, Angela AU - Pirillo A FAU - Chiesa, Giulia AU - Chiesa G FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Letter DEP - 20130423 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Receptors, IgG) SB - IM MH - Female MH - Humans MH - Hypoalphalipoproteinemias/*blood MH - Lipopolysaccharide Receptors/*biosynthesis MH - Male MH - Middle Aged MH - Monocytes/*metabolism MH - Receptors, IgG/*biosynthesis OTO - NOTNLM OT - ApoA- OT - HDL OT - Hypoalphalipoproteinemia monocytes OT - Immunity EDAT- 2013/04/30 06:00 MHDA- 2014/12/19 06:00 CRDT- 2013/04/30 06:00 PHST- 2012/12/31 00:00 [received] PHST- 2013/03/29 00:00 [accepted] PHST- 2013/04/30 06:00 [entrez] PHST- 2013/04/30 06:00 [pubmed] PHST- 2014/12/19 06:00 [medline] AID - S0167-5273(13)00534-2 [pii] AID - 10.1016/j.ijcard.2013.03.103 [doi] PST - ppublish SO - Int J Cardiol. 2013 Oct 3;168(3):2886-9. doi: 10.1016/j.ijcard.2013.03.103. Epub 2013 Apr 23. PMID- 24075740 OWN - NLM STAT- MEDLINE DCOM- 20140519 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 230 IP - 2 DP - 2013 Oct TI - Long-term use of statins reduces the risk of hospitalization for dementia. PG - 171-6 LID - 10.1016/j.atherosclerosis.2013.07.009 [doi] LID - S0021-9150(13)00414-0 [pii] AB - BACKGROUND: Dementia is a major public health problem because of its high prevalence in elderly individuals, particularly in the growing category of subjects aged 80 years or more. There is accumulating evidence that cholesterol may be implicated in the pathogenesis of dementia, and this has led us to assess the relationship between time spent with statins available and the risk of hospitalization for dementia. METHODS: A population-based, nested case-control study was carried out by including the cohort of 152,729 patients from Lombardy (Italy) aged 40 years or older who were newly treated with statins between 2003 and 2004. Cases were the 1380 patients who experienced hospitalization for dementia disease from initial prescription until 2010. Up to twenty controls were randomly selected for each case. Logistic regression was used to model the risk of dementia associated with the cumulative time during which statins were available. Monte-Carlo and rule-out sensitivity analyses were performed to account for unmeasured confounders. RESULTS: Compared with patients who had very short statins coverage (less than 6 months), those on 7-24, 25-48, and >48 months of coverage respectively had risk reductions of 15% (OR: 0.85; 95% CI: 0.74 to 0.98), 28% (OR: 0.72; 95% CI: 0.61 to 0.85), and 25% (OR: 0.75; 95% CI: 0.61 to 0.94). Simvastatin and atorvastatin were both associated with a reduced risk of dementia, while no similar evidence was observed for fluvastatin and pravastatin. CONCLUSIONS: Long-term use of statins seems effective for the prevention of dementia. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy. Electronic address: giovanni.corrao@unimib.it. FAU - Ibrahim, Buthaina AU - Ibrahim B FAU - Nicotra, Federica AU - Nicotra F FAU - Zambon, Antonella AU - Zambon A FAU - Merlino, Luca AU - Merlino L FAU - Pasini, Thea Scognamiglio AU - Pasini TS FAU - Catapano, Alberico L AU - Catapano AL FAU - Mancia, Giuseppe AU - Mancia G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130726 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Fatty Acids, Monounsaturated) RN - 0 (Heptanoic Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Indoles) RN - 0 (Pyrroles) RN - 4L066368AS (Fluvastatin) RN - A0JWA85V8F (Atorvastatin) RN - AGG2FN16EV (Simvastatin) RN - KXO2KT9N0G (Pravastatin) SB - IM CIN - Atherosclerosis. 2013 Oct;230(2):397-8. PMID: 24075773 MH - Adult MH - Aged MH - Aged, 80 and over MH - Atorvastatin MH - Case-Control Studies MH - Dementia/complications/*prevention & control MH - Fatty Acids, Monounsaturated/therapeutic use MH - Female MH - Fluvastatin MH - Heptanoic Acids/therapeutic use MH - Hospitalization MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypercholesterolemia/complications/drug therapy MH - Indoles/therapeutic use MH - Italy/epidemiology MH - Logistic Models MH - Male MH - Middle Aged MH - Pravastatin/therapeutic use MH - Pyrroles/therapeutic use MH - Risk MH - Simvastatin/therapeutic use MH - Time Factors OTO - NOTNLM OT - Alzheimer's disease OT - Dementia OT - Healthcare Utilization Database OT - Lipid-lowering agents OT - Monte-Carlo sensitivity analysis OT - Record linkage OT - Rule-out sensitivity analysis OT - Statins OT - Unmeasured confounders EDAT- 2013/10/01 06:00 MHDA- 2014/05/20 06:00 CRDT- 2013/10/01 06:00 PHST- 2013/03/12 00:00 [received] PHST- 2013/06/17 00:00 [revised] PHST- 2013/07/11 00:00 [accepted] PHST- 2013/10/01 06:00 [entrez] PHST- 2013/10/01 06:00 [pubmed] PHST- 2014/05/20 06:00 [medline] AID - S0021-9150(13)00414-0 [pii] AID - 10.1016/j.atherosclerosis.2013.07.009 [doi] PST - ppublish SO - Atherosclerosis. 2013 Oct;230(2):171-6. doi: 10.1016/j.atherosclerosis.2013.07.009. Epub 2013 Jul 26. PMID- 23607805 OWN - NLM STAT- MEDLINE DCOM- 20131104 LR - 20171213 IS - 1365-2796 (Electronic) IS - 0954-6820 (Linking) VI - 274 IP - 3 DP - 2013 Sep TI - High density lipoprotein cholesterol levels are an independent predictor of the progression of chronic kidney disease. PG - 252-62 LID - 10.1111/joim.12081 [doi] AB - OBJECTIVES: Patients with chronic kidney disease (CKD) often present with reduced plasma HDL cholesterol (HDL-C) levels. Whether this reduction in an epiphenomenon or is involved in disease progression is unclear. The aim of this study was to investigate the relation between HDL-C levels/function and CKD progression in patients with different degrees of disease. DESIGN: A total of 176 patients with CKD [glomerular filtration rate (GFR) 50.3 +/- 29.1 mL min(-)(1)] were recruited and followed for up to 84 months. Lipid profile, metabolic status and kidney function were evaluated at predetermined times. Age-matched control subjects were selected from the PLIC study (n = 453). Scavenger receptor class B member 1 (SR-BI) and ATP-binding cassette transporter A1 (ABCA-1)-dependent efflux of cholesterol were measured in CKD patients and in age-matched control subjects. RESULTS: Low HDL-C levels, diabetes and hypertension were associated with reduced GFR. At follow-up, low HDL-C levels were associated with earlier entry in dialysis or doubling of the plasma creatinine level (P = 0.017); HDL-C levels were the only lipid parameter that affected the progression of CKD (hazard ratio 0.951, 95% confidence interval 0.917-0.986, P = 0.007), independently of the presence of diabetes. Only SR-BI-mediated serum cholesterol efflux was significantly reduced in the group of CKD patients with low HDL-C levels compared to the control group. CONCLUSIONS: CKD patients with low levels of plasma HDL-C have a poor prognosis. HDL functionality is also impaired in renal dysfunction. These data support the relevance of HDL in influencing CKD progression. CI - (c) 2013 The Association for the Publication of the Journal of Internal Medicine. FAU - Baragetti, A AU - Baragetti A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Norata, G D AU - Norata GD FAU - Sarcina, C AU - Sarcina C FAU - Rastelli, F AU - Rastelli F FAU - Grigore, L AU - Grigore L FAU - Garlaschelli, K AU - Garlaschelli K FAU - Uboldi, P AU - Uboldi P FAU - Baragetti, I AU - Baragetti I FAU - Pozzi, C AU - Pozzi C FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130511 PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Cholesterol, HDL) RN - 0 (Scavenger Receptors, Class B) RN - AYI8EX34EU (Creatinine) SB - IM MH - ATP-Binding Cassette Transporters/blood MH - Aged MH - Case-Control Studies MH - Cholesterol, HDL/*blood MH - Creatinine/blood MH - Disease Progression MH - Female MH - Humans MH - Kidney Function Tests MH - Male MH - Predictive Value of Tests MH - Prognosis MH - Prospective Studies MH - ROC Curve MH - Regression Analysis MH - Renal Insufficiency, Chronic/*blood/*physiopathology MH - Risk Factors MH - Scavenger Receptors, Class B/blood OTO - NOTNLM OT - ABCA-1 OT - HDL OT - SR-BI OT - cholesterol efflux OT - chronic kidney disease OT - dialysis EDAT- 2013/04/24 06:00 MHDA- 2013/11/05 06:00 CRDT- 2013/04/24 06:00 PHST- 2013/04/24 06:00 [entrez] PHST- 2013/04/24 06:00 [pubmed] PHST- 2013/11/05 06:00 [medline] AID - 10.1111/joim.12081 [doi] PST - ppublish SO - J Intern Med. 2013 Sep;274(3):252-62. doi: 10.1111/joim.12081. Epub 2013 May 11. PMID- 23696250 OWN - NLM STAT- MEDLINE DCOM- 20140422 LR - 20171116 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 21 IP - 9 DP - 2013 Sep TI - Abdominal visceral fat measurement using dual-energy X-ray: association with cardiometabolic risk factors. PG - 1798-802 LID - 10.1002/oby.20223 [doi] AB - OBJECTIVE: To examine the association between cardiometabolic risk factors and visceral adipose tissue (VAT) measurements using a dual-energy X-ray absorptiometry (DXA) based approach. DESIGN AND METHODS: An analysis of cross-sectional relationships between DXA VAT measured using CoreScan (GE Healthcare) and cardiometabolic indicators was conducted on a sample of 939 subjects (541 females and 398 males; average age, 56 years; average BMI, 26 kg/m2) who had previously undergone a total body DXA scan as well as measurements of key cardiometabolic risk factors. RESULTS: Sex-specific, age-adjusted multivariable regression analysis showed that for both men and women, DXA VAT was significantly associated with increased odds of hypertension, impaired fasting glucose, metabolic syndrome, and type 2 diabetes (P < 0.001). After additional model adjustment for BMI and waist circumference, the odds ratio (per SD change in VAT) for type 2 diabetes was 2.07 for women and 2.25 for men. Similarly, the odds ratio for metabolic syndrome for women was 3.46 and for men was 1.75. CONCLUSIONS: VAT measured using DXA showed a significant association with cardiometabolic risk factors and disease. These relationships persist after statistical adjustment for age, BMI, and waist circumference. DXA VAT may provide a new accessible option for quantifying VAT-related cardiometabolic risk. CI - Copyright (c) 2012 The Obesity Society. FAU - Rothney, Megan P AU - Rothney MP AD - Computational Biology and Biostatistics Laboratory, GE Global Research Center, Niskayuna, New York, USA. FAU - Catapano, Alberico L AU - Catapano AL FAU - Xia, Jin AU - Xia J FAU - Wacker, Wynn K AU - Wacker WK FAU - Tidone, Cristina AU - Tidone C FAU - Grigore, Liliana AU - Grigore L FAU - Xia, Yi AU - Xia Y FAU - Ergun, David L AU - Ergun DL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130521 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Blood Glucose) SB - IM MH - Absorptiometry, Photon MH - *Adiposity MH - Adult MH - Aged MH - Aged, 80 and over MH - Blood Glucose/metabolism MH - Body Mass Index MH - Cardiovascular Diseases/blood/diagnostic imaging/*etiology MH - Diabetes Mellitus, Type 2/blood/diagnostic imaging/*etiology MH - Fasting MH - Female MH - Glucose Intolerance/blood/diagnostic imaging/etiology MH - Humans MH - Hypertension/blood/diagnostic imaging/etiology MH - Intra-Abdominal Fat/*diagnostic imaging MH - Male MH - Metabolic Syndrome/blood/diagnostic imaging/*etiology MH - Middle Aged MH - Multivariate Analysis MH - Obesity, Abdominal/blood/*complications/diagnostic imaging MH - Odds Ratio MH - Regression Analysis MH - Risk Factors MH - Sex Factors MH - Waist Circumference MH - Young Adult EDAT- 2013/05/23 06:00 MHDA- 2014/04/23 06:00 CRDT- 2013/05/23 06:00 PHST- 2012/08/10 00:00 [received] PHST- 2012/11/19 00:00 [accepted] PHST- 2013/05/23 06:00 [entrez] PHST- 2013/05/23 06:00 [pubmed] PHST- 2014/04/23 06:00 [medline] AID - 10.1002/oby.20223 [doi] PST - ppublish SO - Obesity (Silver Spring). 2013 Sep;21(9):1798-802. doi: 10.1002/oby.20223. Epub 2013 May 21. PMID- 23910046 OWN - NLM STAT- MEDLINE DCOM- 20140519 LR - 20130930 IS - 1532-2823 (Electronic) IS - 0952-3278 (Linking) VI - 89 IP - 4 DP - 2013 Sep TI - Different patterns characterize Omega 6 and Omega 3 long chain polyunsaturated fatty acid levels in blood from Italian infants, children, adults and elderly. PG - 215-20 LID - 10.1016/j.plefa.2013.06.009 [doi] LID - S0952-3278(13)00140-3 [pii] AB - Long chain polyunsaturated fatty acids (LC-PUFA), especially the Omega 3, modulate key functions in the body. Their circulating levels are representative of their "status", and may vary at different ages. We have compared the FA status in Italian subjects from neonates to adulthood, assessed through FA analysis of blood drops from fingertips. Data from four cohorts of Italian subjects (total number 1835), have been pooled in four age-groups: neonates (4 days, n=81), children (2-9 years, n=728), adults (40-59 years, n=434) and elderly (60-79 years, n=592). LC-PUFA of both series (Omega 3 and 6) are higher in the blood of neonates than at subsequent ages, reflecting the efficient transfer of these FA from mothers to the fetus. In contrast, the lowest levels of Omega 3 PUFA, especially of DHA, are found in children, probably reflecting inadequate dietary intakes, with possible consequences on the health status at subsequent ages. CI - (c) 2013 Elsevier Ltd. All rights reserved. FAU - Rise, P AU - Rise P AD - DiSFeB, Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti 9, Milan, Italy. Electronic address: patrizia.rise@unimi.it. FAU - Tragni, E AU - Tragni E FAU - Ghezzi, S AU - Ghezzi S FAU - Agostoni, C AU - Agostoni C FAU - Marangoni, F AU - Marangoni F FAU - Poli, A AU - Poli A FAU - Catapano, A L AU - Catapano AL FAU - Siani, A AU - Siani A FAU - Iacoviello, L AU - Iacoviello L FAU - Galli, C AU - Galli C CN - IDEFICS Consortium CN - CHECK group LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130801 PL - Scotland TA - Prostaglandins Leukot Essent Fatty Acids JT - Prostaglandins, leukotrienes, and essential fatty acids JID - 8802730 RN - 0 (Fatty Acids, Monounsaturated) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fatty Acids, Omega-6) RN - 27YG812J1I (Arachidonic Acid) RN - 9KJL21T0QJ (Linoleic Acid) SB - IM MH - Adult MH - Age Factors MH - Aged MH - Arachidonic Acid/blood MH - Child MH - Child, Preschool MH - Fatty Acids, Monounsaturated/blood MH - Fatty Acids, Omega-3/*blood MH - Fatty Acids, Omega-6/*blood MH - Humans MH - Infant, Newborn MH - Italy MH - Linoleic Acid/blood MH - Middle Aged OTO - NOTNLM OT - AA OT - ALA OT - Adults OT - Blood lipids OT - Children OT - DHA OT - EPA OT - Elderly OT - FA OT - Fatty acid status OT - LA OT - LC-PUFA OT - MUFA OT - Neonates OT - PL OT - Polyunsaturated fatty acids OT - SFA OT - WB OT - alpha-linolenic acid OT - arachidonic acid OT - docosahexaenoic acid OT - eicosapentaenoic acid OT - fatty acids OT - linoleic acid OT - long-chain polyunsaturated fatty acids OT - monounsaturated fatty acids OT - phospholipids OT - saturated fatty acids OT - whole blood EDAT- 2013/08/06 06:00 MHDA- 2014/05/20 06:00 CRDT- 2013/08/06 06:00 PHST- 2013/02/13 00:00 [received] PHST- 2013/06/28 00:00 [revised] PHST- 2013/06/29 00:00 [accepted] PHST- 2013/08/06 06:00 [entrez] PHST- 2013/08/06 06:00 [pubmed] PHST- 2014/05/20 06:00 [medline] AID - S0952-3278(13)00140-3 [pii] AID - 10.1016/j.plefa.2013.06.009 [doi] PST - ppublish SO - Prostaglandins Leukot Essent Fatty Acids. 2013 Sep;89(4):215-20. doi: 10.1016/j.plefa.2013.06.009. Epub 2013 Aug 1. PMID- 23958480 OWN - NLM STAT- MEDLINE DCOM- 20140317 LR - 20140401 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 14 IP - 2 DP - 2013 Aug TI - Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]. PG - 243-51 LID - 10.1016/S1567-5688(13)70005-9 [doi] LID - S1567-5688(13)70005-9 [pii] AB - BACKGROUND: Although omega-3 fatty acids have well documented properties which would reduce the cardiovascular (CV) disease risk, the evidence from randomized controlled trials (RCTs) remains inconclusive. We performed a meta-analysis of the available RCTs for investigating the CV preventive effect of administrating at least 1 gram/day, and for at least 1 year, omega-3 fatty acid supplements to patients with existing CV disease. METHODS: RCTs published up to March 2013 were searched from PubMed, EMBASE, and the Cochrane Library. Two of us independently reviewed and selected eligible trials. RESULTS: Of 360 articles retrieved, 11 randomized, double-blind, placebo controlled trials fulfilling inclusion criteria, overall involving 15,348 patients with a history of CV disease, were considered in the final analyses. No statistically significant association was observed for all-cause mortality (RR, 0.89; 95% CI, 0.78 to 1.02) and stroke (RR, 1.31; 95% CI, 0.90 to 1.90). Conversely, statistically significant protective effects were observed for cardiac death (RR, 0.68; 95% CI, 0.56 to 0.83), sudden death (RR, 0.67; 95% CI, 0.52 to 0.87), and myocardial infarction (RR, 0.75; 95% CI, 0.63 to 0.88). CONCLUSION: Overall, our results supply evidence that long-term effect of high dose omega-3 fatty acid supplementation may be beneficial for the onset of cardiac death, sudden death and myocardial infarction among patients with a history of cardiovascular disease. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Casula, Manuela AU - Casula M AD - Centre of Epidemiology and Preventive Pharmacology-SEFAP, Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. sefap@unimi.it FAU - Soranna, Davide AU - Soranna D FAU - Catapano, Alberico L AU - Catapano AL FAU - Corrao, Giovanni AU - Corrao G LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Fatty Acids, Omega-3) SB - IM EIN - Atheroscler Suppl. 2014 Mar;233(1):122 MH - Cardiovascular Diseases/diagnosis/*drug therapy/mortality MH - Disease Progression MH - Double-Blind Method MH - Fatty Acids, Omega-3/*therapeutic use MH - Humans MH - Odds Ratio MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Secondary Prevention/*methods MH - Treatment Outcome OTO - NOTNLM OT - Cardiovascular disease OT - Meta-analysis OT - Omega-3 fatty acid OT - Secondary prevention OT - Supplementation EDAT- 2013/08/21 06:00 MHDA- 2014/03/19 06:00 CRDT- 2013/08/21 06:00 PHST- 2013/08/21 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2014/03/19 06:00 [medline] AID - S1567-5688(13)70005-9 [pii] AID - 10.1016/S1567-5688(13)70005-9 [doi] PST - ppublish SO - Atheroscler Suppl. 2013 Aug;14(2):243-51. doi: 10.1016/S1567-5688(13)70005-9. PMID- 23958479 OWN - NLM STAT- MEDLINE DCOM- 20140317 LR - 20151119 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 14 IP - 2 DP - 2013 Aug TI - Omega-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia. PG - 237-42 LID - 10.1016/S1567-5688(13)70004-7 [doi] LID - S1567-5688(13)70004-7 [pii] AB - Epidemiological studies have established an association between high triglycerides (TG) plasma levels and increased cardiovascular risk. Increased TG levels, commonly coupled with low HDL-C levels, are common in high cardiovascular risk subjects including those with dyslipidemia, metabolic syndrome and type 2 diabetes. Management of hypertriglyceridemia (HTG) includes lifestyle modification for mild-to-moderate HTG and pharmacological therapies for the treatment of high and very high TG levels. Among drugs, fibrates, nicotinic acid and omega-3 polyunsaturated fatty acids may be considered. Omega-3 fatty acids reduce plasma TG levels by several mechanisms; beside the effects on TG, omega-3 can also influence the levels of other lipids and lipoproteins including HDL-C and LDL-C. Clinical trials have also shown that omega-3 fatty acid supplementation is effective also when added in combination with other lipid-lowering drugs. These findings suggest that omega-3 fatty acids may be usefully considered for the management of high TG levels. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Biomarkers) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Triglycerides) SB - IM MH - Atherosclerosis/blood/*drug therapy/etiology MH - Biomarkers/blood MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Dyslipidemias/blood/complications/*drug therapy MH - Fatty Acids, Omega-3/*therapeutic use MH - Humans MH - Treatment Outcome MH - Triglycerides/blood OTO - NOTNLM OT - Dyslipidemia OT - Hypertriglyceridemia OT - Omega-3 polyunsaturated fatty acids OT - Triglycerides EDAT- 2013/08/21 06:00 MHDA- 2014/03/19 06:00 CRDT- 2013/08/21 06:00 PHST- 2013/08/21 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2014/03/19 06:00 [medline] AID - S1567-5688(13)70004-7 [pii] AID - 10.1016/S1567-5688(13)70004-7 [doi] PST - ppublish SO - Atheroscler Suppl. 2013 Aug;14(2):237-42. doi: 10.1016/S1567-5688(13)70004-7. PMID- 23509227 OWN - NLM STAT- MEDLINE DCOM- 20140116 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 34 IP - 24 DP - 2013 Jun TI - New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs. PG - 1783-9 LID - 10.1093/eurheartj/eht088 [doi] AB - Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy. danilo.norata@unimi.it FAU - Ballantyne, Christie M AU - Ballantyne CM FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130318 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Azetidines) RN - 0 (BMS201038) RN - 0 (Benzimidazoles) RN - 0 (Carrier Proteins) RN - 0 (Cholesterol, LDL) RN - 0 (Dicarboxylic Acids) RN - 0 (Fatty Acids) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoprotein(a)) RN - 0 (Oligonucleotides) RN - 0 (Oxazolidinones) RN - 0 (microsomal triglyceride transfer protein) RN - 12794-10-4 (Benzodiazepines) RN - 1EJ6Z6Q368 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) RN - 51XWV9K850 (evacetrapib) RN - 9GJ8S4GU0M (mipomersen) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EOR26LQQ24 (Ezetimibe) RN - P7T269PR6S (anacetrapib) SB - IM MH - Azetidines/therapeutic use MH - Benzimidazoles/therapeutic use MH - Benzodiazepines/therapeutic use MH - Carrier Proteins/antagonists & inhibitors MH - Cholesterol, LDL/antagonists & inhibitors/*drug effects MH - Dicarboxylic Acids/therapeutic use MH - Dyslipidemias/*drug therapy MH - Ezetimibe MH - Fatty Acids/therapeutic use MH - Humans MH - Hypolipidemic Agents/*therapeutic use MH - Lipoprotein(a)/antagonists & inhibitors/*drug effects MH - Oligonucleotides/therapeutic use MH - Oxazolidinones/therapeutic use MH - Proprotein Convertase 9 MH - Proprotein Convertases/antagonists & inhibitors MH - Serine Endopeptidases PMC - PMC3857929 OTO - NOTNLM OT - Apolipoprotein B OT - Dyslipidaemia OT - PCSK9 OT - Pharmacology EDAT- 2013/03/20 06:00 MHDA- 2014/01/17 06:00 CRDT- 2013/03/20 06:00 PHST- 2013/03/20 06:00 [entrez] PHST- 2013/03/20 06:00 [pubmed] PHST- 2014/01/17 06:00 [medline] AID - eht088 [pii] AID - 10.1093/eurheartj/eht088 [doi] PST - ppublish SO - Eur Heart J. 2013 Jun;34(24):1783-9. doi: 10.1093/eurheartj/eht088. Epub 2013 Mar 18. PMID- 23642930 OWN - NLM STAT- MEDLINE DCOM- 20140130 LR - 20171116 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 23 IP - 6 DP - 2013 Jun TI - Moderate alcohol use and health: a consensus document. PG - 487-504 LID - 10.1016/j.numecd.2013.02.007 [doi] LID - S0939-4753(13)00067-7 [pii] AB - AIMS: The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS: In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS: The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Poli, A AU - Poli A AD - NFI (Nutrition Foundation of Italy), Viale Tunisia 38, 20124 Milan, Italy. poli@nutrition-foundation.it FAU - Marangoni, F AU - Marangoni F FAU - Avogaro, A AU - Avogaro A FAU - Barba, G AU - Barba G FAU - Bellentani, S AU - Bellentani S FAU - Bucci, M AU - Bucci M FAU - Cambieri, R AU - Cambieri R FAU - Catapano, A L AU - Catapano AL FAU - Costanzo, S AU - Costanzo S FAU - Cricelli, C AU - Cricelli C FAU - de Gaetano, G AU - de Gaetano G FAU - Di Castelnuovo, A AU - Di Castelnuovo A FAU - Faggiano, P AU - Faggiano P FAU - Fattirolli, F AU - Fattirolli F FAU - Fontana, L AU - Fontana L FAU - Forlani, G AU - Forlani G FAU - Frattini, S AU - Frattini S FAU - Giacco, R AU - Giacco R FAU - La Vecchia, C AU - La Vecchia C FAU - Lazzaretto, L AU - Lazzaretto L FAU - Loffredo, L AU - Loffredo L FAU - Lucchin, L AU - Lucchin L FAU - Marelli, G AU - Marelli G FAU - Marrocco, W AU - Marrocco W FAU - Minisola, S AU - Minisola S FAU - Musicco, M AU - Musicco M FAU - Novo, S AU - Novo S FAU - Nozzoli, C AU - Nozzoli C FAU - Pelucchi, C AU - Pelucchi C FAU - Perri, L AU - Perri L FAU - Pieralli, F AU - Pieralli F FAU - Rizzoni, D AU - Rizzoni D FAU - Sterzi, R AU - Sterzi R FAU - Vettor, R AU - Vettor R FAU - Violi, F AU - Violi F FAU - Visioli, F AU - Visioli F LA - eng PT - Journal Article PT - Review DEP - 20130501 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Biomarkers) SB - IM CIN - Nutr Metab Cardiovasc Dis. 2014 Jan;24(1):e4-5. PMID: 24418383 CIN - Nutr Metab Cardiovasc Dis. 2014 Jul;24(7):e25-6. PMID: 24838174 MH - Alcohol Drinking/*adverse effects MH - Alcoholic Beverages/*adverse effects MH - Biomarkers/blood MH - Cardiovascular Diseases/epidemiology MH - Dementia/epidemiology MH - Diabetes Mellitus/epidemiology MH - Humans MH - Insulin Resistance MH - Life Style MH - Liver Diseases/epidemiology MH - Metabolic Syndrome/epidemiology MH - Neoplasms/epidemiology MH - Obesity/epidemiology MH - Osteoporosis/epidemiology MH - Risk Factors EDAT- 2013/05/07 06:00 MHDA- 2014/01/31 06:00 CRDT- 2013/05/07 06:00 PHST- 2012/11/13 00:00 [received] PHST- 2013/01/29 00:00 [revised] PHST- 2013/02/27 00:00 [accepted] PHST- 2013/05/07 06:00 [entrez] PHST- 2013/05/07 06:00 [pubmed] PHST- 2014/01/31 06:00 [medline] AID - S0939-4753(13)00067-7 [pii] AID - 10.1016/j.numecd.2013.02.007 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2013 Jun;23(6):487-504. doi: 10.1016/j.numecd.2013.02.007. Epub 2013 May 1. PMID- 23466067 OWN - NLM STAT- MEDLINE DCOM- 20131105 LR - 20161125 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 228 IP - 1 DP - 2013 May TI - The safety of therapeutic monoclonal antibodies: implications for cardiovascular disease and targeting the PCSK9 pathway. PG - 18-28 LID - 10.1016/j.atherosclerosis.2013.01.044 [doi] LID - S0021-9150(13)00106-8 [pii] AB - Monoclonal antibodies (mAbs) are established therapies for many conditions, including cancers, autoimmune conditions and infectious diseases. mAbs can offer benefits over conventional pharmacotherapy in terms of potency, dosing frequency and specificity for their target antigen. Mouse-derived antibodies were initially used in humans; however, patients often developed human anti-mouse antibodies, resulting in rapid antibody clearance (and a resulting loss of efficacy) and hypersensitivity reactions. Chimeric, humanized, and fully human antibodies were thus developed, with increasing amounts of human sequence, to reduce immunogenicity. Although generally well tolerated, mAbs may be associated with adverse events (AEs). Many AEs are target-related, and will be specific to the antibody target and the therapeutic area of use. However, off-target AEs, such as hypersensitivity reactions, are observed with many antibodies. Within the realm of cardiovascular medicine, new antibody-based therapies are under investigation to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma LDL-C levels by increasing degradation of the LDL receptor (LDLR). Therefore, inhibition of the interaction between PCSK9 and the LDLR with mAbs targeting PCSK9 has great potential for patients with hypercholesterolaemia. Early clinical phase studies suggest these mAbs are effective and well tolerated; however, further studies are required to assess their long-term safety. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Catapano, A L AU - Catapano AL AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; IRCCS Multimedica, Italy. Alberico.catapano@unimi.it FAU - Papadopoulos, N AU - Papadopoulos N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130208 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Antibodies, Monoclonal) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Animals MH - Antibodies, Monoclonal/*administration & dosage/*adverse effects MH - Cardiovascular Diseases/*drug therapy/immunology/metabolism MH - Humans MH - Hypercholesterolemia/*drug therapy/immunology/metabolism MH - Proprotein Convertase 9 MH - Proprotein Convertases/immunology/*metabolism MH - Serine Endopeptidases/immunology/*metabolism EDAT- 2013/03/08 06:00 MHDA- 2013/11/06 06:00 CRDT- 2013/03/08 06:00 PHST- 2012/10/08 00:00 [received] PHST- 2013/01/09 00:00 [revised] PHST- 2013/01/29 00:00 [accepted] PHST- 2013/03/08 06:00 [entrez] PHST- 2013/03/08 06:00 [pubmed] PHST- 2013/11/06 06:00 [medline] AID - S0021-9150(13)00106-8 [pii] AID - 10.1016/j.atherosclerosis.2013.01.044 [doi] PST - ppublish SO - Atherosclerosis. 2013 May;228(1):18-28. doi: 10.1016/j.atherosclerosis.2013.01.044. Epub 2013 Feb 8. PMID- 23593165 OWN - NLM STAT- MEDLINE DCOM- 20131104 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 4 DP - 2013 TI - -374 T/A RAGE polymorphism is associated with chronic kidney disease progression in subjects affected by nephrocardiovascular disease. PG - e60089 LID - 10.1371/journal.pone.0060089 [doi] AB - BACKGROUND: Chronic kidney disease (CKD) patients present elevated advanced glycation end products (AGEs) blood levels. AGEs promote inflammation through binding to their receptor (RAGE), located on the membrane of mesangial cells, endothelial cells and macrophages. Several genetic polymorphisms influence RAGE transcription, expression and activity, including the substitution of a thymine with an adenine (T/A) in the position -374 of the gene promoter of RAGE. Our study investigates the role of -374 T/A RAGE polymorphism in CKD progression in subjects affected by nephrocardiovascular disease. METHODS: 174 patients (119 males (68.4%) mean age 67.2+/-0.88 years; 55 females (31.6%): mean age 65.4+/-1.50 years) affected by mild to moderate nephrocardiovascular CKD were studied. Each subject was prospectively followed for 84 months, every 6-9 months. The primary endpoint of the study was a rise of serum creatinine concentrations above 50% of basal values or end stage renal disease. RESULTS: Carriers of the A/A and T/A genotype presented higher plasma levels of interleukin 6 (A/A 29.5+/-15.83; T/A 30.0+/-7.89, vs T/T 12.3+/-5.04 p = 0.01 for both) and Macrophages chemoattractant protein 1 (A/A 347.1+/-39.87; T/A 411.8+/-48.41, vs T/T 293.5+/-36.20, p = 0.04 for both) than T/T subjects. Carriers of the A allele presented a faster CKD progression than wild type patients (Log-Rank test: Chi square = 6.84, p = 0,03). Cox regression showed that -374 T/A RAGE polymorphism (p = 0.037), albuminuria (p = 0.01) and LDL cholesterol (p = 0.038) were directly associated with CKD progression. HDL cholesterol (p = 0.022) and BMI (p = 0.04) were inversely related to it. No relationship was found between circulating RAGE and renal function decline. CONCLUSIONS: -374 T/A RAGE polymorphism could be associated with CKD progression and inflammation. Further studies should confirm this finding and address whether inhibiting RAGE downstream signalling would be beneficial for CKD progression. FAU - Baragetti, Ivano AU - Baragetti I AD - Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy. ivano.baragetti@icp.mi.it FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Sarcina, Cristina AU - Sarcina C FAU - Baragetti, Andrea AU - Baragetti A FAU - Rastelli, Francesco AU - Rastelli F FAU - Buzzi, Laura AU - Buzzi L FAU - Grigore, Liliana AU - Grigore L FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Pozzi, Claudio AU - Pozzi C FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article DEP - 20130404 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Receptor for Advanced Glycation End Products) SB - IM MH - Aged MH - Aged, 80 and over MH - Alleles MH - Cardiovascular Diseases/*complications/drug therapy MH - Disease Progression MH - Female MH - Genotype MH - Humans MH - Kidney Function Tests MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Prognosis MH - Receptor for Advanced Glycation End Products/*genetics/metabolism MH - Renal Insufficiency, Chronic/*complications/drug therapy/*genetics/mortality PMC - PMC3617170 EDAT- 2013/04/18 06:00 MHDA- 2013/11/05 06:00 CRDT- 2013/04/18 06:00 PHST- 2012/12/07 00:00 [received] PHST- 2013/02/23 00:00 [accepted] PHST- 2013/04/18 06:00 [entrez] PHST- 2013/04/18 06:00 [pubmed] PHST- 2013/11/05 06:00 [medline] AID - 10.1371/journal.pone.0060089 [doi] AID - PONE-D-12-39293 [pii] PST - epublish SO - PLoS One. 2013 Apr 4;8(4):e60089. doi: 10.1371/journal.pone.0060089. Print 2013. PMID- 23260873 OWN - NLM STAT- MEDLINE DCOM- 20130916 LR - 20181113 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 227 IP - 2 DP - 2013 Apr TI - MicroRNAs and lipoproteins: a connection beyond atherosclerosis? PG - 209-15 LID - 10.1016/j.atherosclerosis.2012.11.019 [doi] LID - S0021-9150(12)00814-3 [pii] AB - MicroRNAs (miRNAs) are short non-coding RNAs involved in the regulation of gene expression at the post-transcriptional level that have been involved in the pathogenesis of a number of cardiovascular diseases. Several miRNAs have been described to finely regulate lipid metabolism and the progression and regression of atherosclerosis including, miR-33, miR-122. Of note miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR-33 approaches are under intensive investigation. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible because lipid-carriers, including lipoproteins, transport and protect miRNAs from degradation in the circulation. This review will present the complex mechanism by which miRNAs regulate lipid metabolism, illustrate how their therapeutical modulation may lead to new treatments for cardiometabolic diseases, and discuss how lipoproteins and other lipid-carriers transport miRNAs in the circulation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. CI - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy. danilo.norata@unimi.it FAU - Sala, Federica AU - Sala F FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Fernandez-Hernando, Carlos AU - Fernandez-Hernando C LA - eng GR - R01 HL106063/HL/NHLBI NIH HHS/United States GR - R01 HL107953/HL/NHLBI NIH HHS/United States GR - R01HL106063/HL/NHLBI NIH HHS/United States GR - R01HL107953/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20121124 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins) RN - 0 (MIRN122 microRNA, human) RN - 0 (MIRN33 microRNA, human) RN - 0 (MicroRNAs) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Atherosclerosis/*metabolism MH - *Gene Expression Regulation MH - Glucose/metabolism MH - Humans MH - Lipid Metabolism MH - Lipoproteins/*metabolism MH - MicroRNAs/*metabolism PMC - PMC4193445 MID - NIHMS629623 EDAT- 2012/12/25 06:00 MHDA- 2013/09/17 06:00 CRDT- 2012/12/25 06:00 PHST- 2012/09/04 00:00 [received] PHST- 2012/11/13 00:00 [revised] PHST- 2012/11/20 00:00 [accepted] PHST- 2012/12/25 06:00 [entrez] PHST- 2012/12/25 06:00 [pubmed] PHST- 2013/09/17 06:00 [medline] AID - S0021-9150(12)00814-3 [pii] AID - 10.1016/j.atherosclerosis.2012.11.019 [doi] PST - ppublish SO - Atherosclerosis. 2013 Apr;227(2):209-15. doi: 10.1016/j.atherosclerosis.2012.11.019. Epub 2012 Nov 24. PMID- 23535734 OWN - NLM STAT- MEDLINE DCOM- 20130521 LR - 20181113 IS - 1546-1718 (Electronic) IS - 1061-4036 (Linking) VI - 45 IP - 4 DP - 2013 Apr TI - Identification of seven loci affecting mean telomere length and their association with disease. PG - 422-7, 427e1-2 LID - 10.1038/ng.2528 [doi] AB - Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 x 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases. FAU - Codd, Veryan AU - Codd V AD - Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. FAU - Nelson, Christopher P AU - Nelson CP FAU - Albrecht, Eva AU - Albrecht E FAU - Mangino, Massimo AU - Mangino M FAU - Deelen, Joris AU - Deelen J FAU - Buxton, Jessica L AU - Buxton JL FAU - Hottenga, Jouke Jan AU - Hottenga JJ FAU - Fischer, Krista AU - Fischer K FAU - Esko, Tonu AU - Esko T FAU - Surakka, Ida AU - Surakka I FAU - Broer, Linda AU - Broer L FAU - Nyholt, Dale R AU - Nyholt DR FAU - Mateo Leach, Irene AU - Mateo Leach I FAU - Salo, Perttu AU - Salo P FAU - Hagg, Sara AU - Hagg S FAU - Matthews, Mary K AU - Matthews MK FAU - Palmen, Jutta AU - Palmen J FAU - Norata, Giuseppe D AU - Norata GD FAU - O'Reilly, Paul F AU - O'Reilly PF FAU - Saleheen, Danish AU - Saleheen D FAU - Amin, Najaf AU - Amin N FAU - Balmforth, Anthony J AU - Balmforth AJ FAU - Beekman, Marian AU - Beekman M FAU - de Boer, Rudolf A AU - de Boer RA FAU - Bohringer, Stefan AU - Bohringer S FAU - Braund, Peter S AU - Braund PS FAU - Burton, Paul R AU - Burton PR FAU - de Craen, Anton J M AU - de Craen AJ FAU - Denniff, Matthew AU - Denniff M FAU - Dong, Yanbin AU - Dong Y FAU - Douroudis, Konstantinos AU - Douroudis K FAU - Dubinina, Elena AU - Dubinina E FAU - Eriksson, Johan G AU - Eriksson JG FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Guo, Dehuang AU - Guo D FAU - Hartikainen, Anna-Liisa AU - Hartikainen AL FAU - Henders, Anjali K AU - Henders AK FAU - Houwing-Duistermaat, Jeanine J AU - Houwing-Duistermaat JJ FAU - Kananen, Laura AU - Kananen L FAU - Karssen, Lennart C AU - Karssen LC FAU - Kettunen, Johannes AU - Kettunen J FAU - Klopp, Norman AU - Klopp N FAU - Lagou, Vasiliki AU - Lagou V FAU - van Leeuwen, Elisabeth M AU - van Leeuwen EM FAU - Madden, Pamela A AU - Madden PA FAU - Magi, Reedik AU - Magi R FAU - Magnusson, Patrik K E AU - Magnusson PK FAU - Mannisto, Satu AU - Mannisto S FAU - McCarthy, Mark I AU - McCarthy MI FAU - Medland, Sarah E AU - Medland SE FAU - Mihailov, Evelin AU - Mihailov E FAU - Montgomery, Grant W AU - Montgomery GW FAU - Oostra, Ben A AU - Oostra BA FAU - Palotie, Aarno AU - Palotie A FAU - Peters, Annette AU - Peters A FAU - Pollard, Helen AU - Pollard H FAU - Pouta, Anneli AU - Pouta A FAU - Prokopenko, Inga AU - Prokopenko I FAU - Ripatti, Samuli AU - Ripatti S FAU - Salomaa, Veikko AU - Salomaa V FAU - Suchiman, H Eka D AU - Suchiman HE FAU - Valdes, Ana M AU - Valdes AM FAU - Verweij, Niek AU - Verweij N FAU - Vinuela, Ana AU - Vinuela A FAU - Wang, Xiaoling AU - Wang X FAU - Wichmann, H-Erich AU - Wichmann HE FAU - Widen, Elisabeth AU - Widen E FAU - Willemsen, Gonneke AU - Willemsen G FAU - Wright, Margaret J AU - Wright MJ FAU - Xia, Kai AU - Xia K FAU - Xiao, Xiangjun AU - Xiao X FAU - van Veldhuisen, Dirk J AU - van Veldhuisen DJ FAU - Catapano, Alberico L AU - Catapano AL FAU - Tobin, Martin D AU - Tobin MD FAU - Hall, Alistair S AU - Hall AS FAU - Blakemore, Alexandra I F AU - Blakemore AI FAU - van Gilst, Wiek H AU - van Gilst WH FAU - Zhu, Haidong AU - Zhu H CN - CARDIoGRAM consortium FAU - Erdmann, Jeanette AU - Erdmann J FAU - Reilly, Muredach P AU - Reilly MP FAU - Kathiresan, Sekar AU - Kathiresan S FAU - Schunkert, Heribert AU - Schunkert H FAU - Talmud, Philippa J AU - Talmud PJ FAU - Pedersen, Nancy L AU - Pedersen NL FAU - Perola, Markus AU - Perola M FAU - Ouwehand, Willem AU - Ouwehand W FAU - Kaprio, Jaakko AU - Kaprio J FAU - Martin, Nicholas G AU - Martin NG FAU - van Duijn, Cornelia M AU - van Duijn CM FAU - Hovatta, Iiris AU - Hovatta I FAU - Gieger, Christian AU - Gieger C FAU - Metspalu, Andres AU - Metspalu A FAU - Boomsma, Dorret I AU - Boomsma DI FAU - Jarvelin, Marjo-Riitta AU - Jarvelin MR FAU - Slagboom, P Eline AU - Slagboom PE FAU - Thompson, John R AU - Thompson JR FAU - Spector, Tim D AU - Spector TD FAU - van der Harst, Pim AU - van der Harst P FAU - Samani, Nilesh J AU - Samani NJ LA - eng GR - 090532/Wellcome Trust/United Kingdom GR - G0902313/Medical Research Council/United Kingdom GR - MR/K014536/1/Medical Research Council/United Kingdom GR - R56 DA012854/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Nat Genet JT - Nature genetics JID - 9216904 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.7.49 (TERT protein, human) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Biomarkers, Tumor/*genetics MH - Case-Control Studies MH - Disease/*genetics MH - Female MH - Genetic Loci/*genetics MH - Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - Humans MH - Leukocytes/*metabolism MH - Male MH - Meta-Analysis as Topic MH - Risk Factors MH - Telomerase/*genetics MH - Telomere/*genetics PMC - PMC4006270 MID - NIHMS571267 EDAT- 2013/03/29 06:00 MHDA- 2013/05/23 06:00 CRDT- 2013/03/29 06:00 PHST- 2012/06/26 00:00 [received] PHST- 2012/12/19 00:00 [accepted] PHST- 2013/03/29 06:00 [entrez] PHST- 2013/03/29 06:00 [pubmed] PHST- 2013/05/23 06:00 [medline] AID - ng.2528 [pii] AID - 10.1038/ng.2528 [doi] PST - ppublish SO - Nat Genet. 2013 Apr;45(4):422-7, 427e1-2. doi: 10.1038/ng.2528. PMID- 23485362 OWN - NLM STAT- MEDLINE DCOM- 20131025 LR - 20130409 IS - 1873-3735 (Electronic) IS - 0165-6147 (Linking) VI - 34 IP - 4 DP - 2013 Apr TI - Gene silencing approaches for the management of dyslipidaemia. PG - 198-205 LID - 10.1016/j.tips.2013.01.010 [doi] LID - S0165-6147(13)00024-2 [pii] AB - The key role of dyslipidaemias in determining cardiovascular risk has been well established, and statins often provide effective therapeutic management. However, many patients do not achieve recommended lipid levels despite maximal therapy, and some cannot tolerate high-dose statin therapy. Recently, genetic insights into mechanisms underlying regulation of lipoprotein metabolism have expanded the potential targets of drug therapy and led to the development of novel agents, including development of gene silencing approaches. These therapeutic options include the modulation of synthesis in the liver, maturation in the circulation, and catabolism of lipoproteins. In this review, we discuss the pharmacological consequences of silencing apolipoprotein B, apolipoprotein (a), microRNA 33, proprotein convertase subtilisin/kexin type 9, and apolipoprotein C-III. New potential targets such as other microRNAs, diacylglycerol acyl transferase-1, and angiopoietin-like protein 3 are also presented. The pharmacological consequences of gene silencing and the advancement of these therapeutic approaches in clinical development will be examined. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. danilo.norata@unimi.it FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130226 PL - England TA - Trends Pharmacol Sci JT - Trends in pharmacological sciences JID - 7906158 RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Dyslipidemias/*genetics/*therapy MH - *Gene Silencing MH - Genetic Therapy/*methods MH - Humans MH - MicroRNAs/administration & dosage/genetics EDAT- 2013/03/15 06:00 MHDA- 2013/10/26 06:00 CRDT- 2013/03/15 06:00 PHST- 2012/10/30 00:00 [received] PHST- 2013/01/29 00:00 [revised] PHST- 2013/01/31 00:00 [accepted] PHST- 2013/03/15 06:00 [entrez] PHST- 2013/03/15 06:00 [pubmed] PHST- 2013/10/26 06:00 [medline] AID - S0165-6147(13)00024-2 [pii] AID - 10.1016/j.tips.2013.01.010 [doi] PST - ppublish SO - Trends Pharmacol Sci. 2013 Apr;34(4):198-205. doi: 10.1016/j.tips.2013.01.010. Epub 2013 Feb 26. PMID- 22777149 OWN - NLM STAT- MEDLINE DCOM- 20130801 LR - 20181113 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 69 IP - 3 DP - 2013 Mar TI - Effect of treatment with pravastatin or ezetimibe on endothelial function in patients with moderate hypercholesterolemia. PG - 341-6 LID - 10.1007/s00228-012-1345-z [doi] AB - BACKGROUND/AIM: Statin treatment improves endothelial function. It is matter of debate, however, if this effect of statins is due to their action on low-density lipoprotein cholesterol (LDL-C) or to other non-lipidic (pleiotropic) effects. The aim of this study was to evaluate whether the effect of pravastatin on endothelial function is mediated by pleiotropic effects. We therefore compared the effect of pravastatin and ezetimibe, a cholesterol absorption inhibitor, at doses yielding similar reductions in LDL-C and examined the effect of the two treatments on flow-mediated dilation (FMD) in hypercholesterolemic subjects. METHODS: A total of 33 moderately hypercholesterolemic patients were randomized into three treatment groups to receive ezetimibe 10 mg/day (n = 10), pravastatin 10 mg/day (n = 13) or no treatment (control, n = 10) for 6 weeks. To assess endothelial function, we determined FMD of the brachial artery non-invasively by high-resolution ultrasound before and after treatment. RESULTS: Ezetimibe and pravastatin treatment reduced LDL-C (mean +/- standard error) to a similar extent (-20.6 +/- 4.1 vs. -24.1 +/- 4.0 %, respectively; P = 0.4771), while no decrease was observed in the control group. FMD increased significantly after treatment with ezetimibe (from 11.4 +/- 5.7 to 16.8 +/- 3.6 %; P = 0.022) and with pravastatin (from 13.7 +/- 4.9 to 17.5 +/- 4.4 %; P = 0.0466), but not in the control group. There were no differences in the endothelial function changes between the two treatment groups. CONCLUSIONS: In this study, two treatments that lower cholesterol via different mechanisms improved endothelial function to a similar extent, suggesting that the observed effect can be explained by the reduction of cholesterol levels. FAU - Grigore, Liliana AU - Grigore L AD - Center for the Study of Atherosclerosis-SISA Lombardia, Bassini Hospital, Via Gorki 50, 20092 Cinisello Balsamo, Milan, Italy. FAU - Raselli, Sara AU - Raselli S FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Redaelli, Laura AU - Redaelli L FAU - Norata, Giuseppe D AU - Norata GD FAU - Pirillo, Angela AU - Pirillo A FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20120710 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Biomarkers) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) RN - EOR26LQQ24 (Ezetimibe) RN - KXO2KT9N0G (Pravastatin) SB - IM MH - Adult MH - Anticholesteremic Agents/*therapeutic use MH - Azetidines/*therapeutic use MH - Biomarkers/blood MH - Brachial Artery/diagnostic imaging/*drug effects/physiopathology MH - Cholesterol/*blood MH - Endothelium, Vascular/diagnostic imaging/*drug effects/physiopathology MH - Ezetimibe MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Hypercholesterolemia/blood/*drug therapy/physiopathology MH - Italy MH - Male MH - Middle Aged MH - Pravastatin/*therapeutic use MH - Severity of Illness Index MH - Treatment Outcome MH - Ultrasonography MH - Vasodilation/*drug effects EDAT- 2012/07/11 06:00 MHDA- 2013/08/02 06:00 CRDT- 2012/07/11 06:00 PHST- 2012/03/27 00:00 [received] PHST- 2012/06/21 00:00 [accepted] PHST- 2012/07/11 06:00 [entrez] PHST- 2012/07/11 06:00 [pubmed] PHST- 2013/08/02 06:00 [medline] AID - 10.1007/s00228-012-1345-z [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2013 Mar;69(3):341-6. doi: 10.1007/s00228-012-1345-z. Epub 2012 Jul 10. PMID- 23040261 OWN - NLM STAT- MEDLINE DCOM- 20130730 LR - 20151119 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 24 IP - 2 DP - 2013 Mar TI - C-reactive protein distribution and correlation with traditional cardiovascular risk factors in the Italian population. PG - 161-6 LID - 10.1016/j.ejim.2012.09.010 [doi] LID - S0953-6205(12)00248-8 [pii] AB - BACKGROUND: C-reactive protein (CRP) increases during an inflammatory response; its plasma levels are believed to be an independent predictor of future atherosclerotic disease. We report the distribution of plasma levels of CRP and its possible relationship with other cardiovascular risk factors in an Italian cohort. METHODS: CRP was assessed in frozen plasma samples of 1949 participants in the CHECK study (2001-2005), which collected clinical and biochemical data from randomly selected subjects (40-79 years) in the setting of Italian general practice. RESULTS: Median CRP (interquartile range) was higher in women (1.42 [0.58-2.86] vs 1.28 [0.58-2.50]; p=.163), in people aged >/= 65 years (1.74 [0.89-3.34] vs 1.11 [0.52-2.45]; p<.001), in patients with obesity (2.37 [1.27-4.15] vs 1.16 [0.52-2.41]; p<.001), metabolic syndrome (2.12 [1.16-3.72] vs 1.10 [0.50-2.38]; p<.001), or higher cardiovascular risk (2.03 [1.01-3.42] vs 1.19 [0.53-2.50]; p<.001). Stepwise regression analysis showed significant associations (R(2)=.264) of circulating log(e)CRP with body mass index, fibrinogen, apoB, age, gender, smoking habits, physical inactivity, creatinine levels, and systolic blood pressure. CONCLUSION: This study provides epidemiological data of CRP in the Italian population and reinforces the existing evidences about the close correlation between CRP and markers of inflammation and adiposity. CI - Copyright (c) 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milano, Italy. FAU - Tragni, Elena AU - Tragni E FAU - Zambon, Antonella AU - Zambon A FAU - Filippi, Alessandro AU - Filippi A FAU - Brignoli, Ovidio AU - Brignoli O FAU - Cricelli, Claudio AU - Cricelli C FAU - Poli, Andrea AU - Poli A FAU - Catapano, Alberico L AU - Catapano AL CN - CHECK group LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20121004 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Biomarkers) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Adult MH - Aged MH - Biomarkers/blood MH - C-Reactive Protein/*metabolism MH - Cardiovascular Diseases/*blood/*epidemiology MH - Female MH - Follow-Up Studies MH - Humans MH - Incidence MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Prognosis MH - Retrospective Studies MH - Risk Assessment/*methods MH - Risk Factors IR - Aalders MA FIR - Aalders, Maria Anna IR - Abbate G FIR - Abbate, Giuseppe IR - Agati R FIR - Agati, Riccardo IR - Alano R FIR - Alano, Raffaele IR - Alba M FIR - Alba, Mauro IR - Alemagna S FIR - Alemagna, Silvia IR - Alunni M FIR - Alunni, Massimo IR - Alvaro A FIR - Alvaro, Antonio IR - Amato F FIR - Amato, Fabio IR - Ammendola E FIR - Ammendola, Erminia IR - Amodeo V FIR - Amodeo, Vincenzo IR - Amoretti G FIR - Amoretti, Giovanni IR - Andrani A FIR - Andrani, Alberto IR - Antiga I FIR - Antiga, Ivo IR - Appolonia G FIR - Appolonia, Giorgio IR - Aramini E FIR - Aramini, Enrico IR - Arisi ME FIR - Arisi, Marco Emilio IR - Artebani A FIR - Artebani, Adriano IR - Atzei M FIR - Atzei, Massimiliano IR - Azzolini M FIR - Azzolini, Micheline IR - Bachetti F FIR - Bachetti, Francesco IR - Bagagli F FIR - Bagagli, Franco IR - Baldicchi L FIR - Baldicchi, Lorella IR - Banzi R FIR - Banzi, Roberta IR - Barba EM FIR - Barba, Ettore Maria IR - Barbato PC FIR - Barbato, Pasquale Claudio IR - Caregnato M FIR - Caregnato, Massimo IR - Cariola G FIR - Cariola, Gianni IR - Carlino S FIR - Carlino, Saverio IR - Carminati LA FIR - Carminati, Luisa Angela IR - Carnelli F FIR - Carnelli, Feliciano IR - Carnesalli F FIR - Carnesalli, Franco IR - Caruso C FIR - Caruso, Ciro IR - Casale E FIR - Casale, Ezio IR - Casini M FIR - Casini, Marcella IR - Cassanelli M FIR - Cassanelli, Marco IR - Castiello ML FIR - Castiello, Maria Luisa IR - Castriotta A FIR - Castriotta, Antonio IR - Catalano D FIR - Catalano, Domenico IR - Cataldi ME FIR - Cataldi, Maria Elvira IR - Ceccarini A FIR - Ceccarini, Agostino IR - Celebrano M FIR - Celebrano, Mario IR - Celora A FIR - Celora, Amedeo IR - Cerracchio A FIR - Cerracchio, Alessandro IR - Cesaro A FIR - Cesaro, Andrea IR - Cesaro F FIR - Cesaro, Federico IR - Chiriatti A FIR - Chiriatti, Alberto IR - Cipriani R FIR - Cipriani, Rosa IR - Collura G FIR - Collura, Giuseppe IR - Colombo V FIR - Colombo, Valter IR - Coluccia S FIR - Coluccia, Salvatore IR - Conte S FIR - Conte, Sergio IR - Corda A FIR - Corda, Andrea IR - Costa R FIR - Costa, Roberto IR - Cottani A FIR - Cottani, Antonio IR - Crivellenti G FIR - Crivellenti, Giuseppe IR - D'Ambrosio G FIR - D'Ambrosio, Gaetano IR - D'Angelo M FIR - D'Angelo, Massimo IR - Dalla Rosa R FIR - Dalla Rosa, Rosanna IR - Damico G FIR - Damico, Giansanto IR - De Andreis Bessone PL FIR - De Andreis Bessone, Pier Luigi IR - Grimaldi E FIR - Grimaldi, Emanuela IR - Grosso M FIR - Grosso, Marco IR - Guarnera L FIR - Guarnera, Lucia IR - Guerra A FIR - Guerra, Antonio IR - Guillaro B FIR - Guillaro, Bruno IR - Gussoni BR FIR - Gussoni, Barbara Rita IR - Ianiro G FIR - Ianiro, Gabriella IR - Ilardi S FIR - Ilardi, Salvatore IR - Imbalzano P FIR - Imbalzano, Pasquale IR - Inguscio C FIR - Inguscio, Cherubino IR - Invernizzi G FIR - Invernizzi, Giovanni IR - Iocca T FIR - Iocca, Tommaso IR - Kos E FIR - Kos, Egidia IR - Barral G FIR - Barral, Gino IR - Battaggia A FIR - Battaggia, Alessandro IR - Battigelli D FIR - Battigelli, Doriano IR - Baudi M FIR - Baudi, Marina IR - Bellumori G FIR - Bellumori, Giovanni IR - Beltrami G FIR - Beltrami, Giuseppe IR - Benincasa AM FIR - Benincasa, Anna Maria IR - Berardi M FIR - Berardi, Mario IR - Berlengiero C FIR - Berlengiero, Claudio IR - Bernardelli S FIR - Bernardelli, Stefano IR - Bernardi G FIR - Bernardi, Giuseppe IR - Bertelle E FIR - Bertelle, Evandro IR - Bettini G FIR - Bettini, Gianluca IR - Bevacqua G FIR - Bevacqua, Giuseppe IR - Bevilacqua S FIR - Bevilacqua, Stefano IR - Bianconi G FIR - Bianconi, Giuseppe IR - Biggioggero G FIR - Biggioggero, Giovanni IR - Bini V FIR - Bini, Vincenzo IR - Bocchino G FIR - Bocchino, Giancarlo IR - Boccone N FIR - Boccone, Nicolfranco IR - Boito G FIR - Boito, Giancarlo IR - Bollo AM FIR - Bollo, Alberto Maria IR - Boncompagni S FIR - Boncompagni, Salvatore IR - Bond G FIR - Bond, Giuseppe IR - Bonesi MG FIR - Bonesi, Maria Grazia IR - Bono G FIR - Bono, Gianfranco IR - De Benedictis A FIR - De Benedictis, Antonio IR - De Conto U FIR - De Conto, Umberto IR - De Mola C FIR - De Mola, Cosimo IR - De Rosa A FIR - De Rosa, Antonio IR - De Tommasi R FIR - De Tommasi, Roberto IR - Del Nero B FIR - Del Nero, Barbara IR - Della Briotta I FIR - Della Briotta, Ivana IR - Dell'Orco MD FIR - Dell'Orco, Mario Domenico IR - Dell'Orco ML FIR - Dell'Orco, Mario Lucio Raffaele IR - Di Candia G FIR - Di Candia, Giuseppe IR - Di Carlo V FIR - Di Carlo, Vittorio IR - Di Febo E FIR - Di Febo, Enrico IR - Di Feo A FIR - Di Feo, Antonio IR - Di Fraia G FIR - Di Fraia, Giovanni IR - Di Fulvio A FIR - Di Fulvio, Aristide IR - Di Nardo D FIR - Di Nardo, Dionisio IR - Dolmetta F FIR - Dolmetta, Franco IR - Donzelli L FIR - Donzelli, Luigi IR - Dughiero F FIR - Dughiero, Fausto IR - Durando A FIR - Durando, Andrea IR - Ercolino L FIR - Ercolino, Luigi IR - Fabbri S FIR - Fabbri, Stelania IR - Fabrizio N FIR - Fabrizio, Nicola IR - Falchi R FIR - Falchi, Raffaello IR - Fariello C FIR - Fariello, Ciro IR - Fascendini E FIR - Fascendini, Emilvio IR - Fasulo S FIR - Fasulo, Serenella IR - Federici L FIR - Federici, Laura IR - Ferioli P FIR - Ferioli, Paolo IR - Ferrari V FIR - Ferrari, Vincenzo IR - Fidelbo M FIR - Fidelbo, Melchiorre IR - Filetti G FIR - Filetti, Giuseppe IR - Filippini G FIR - Filippini, Giovanni IR - Fogher M FIR - Fogher, Michele IR - Franchini CA FIR - Franchini, Carlo Andrea IR - Mantovani L FIR - Mantovani, Licia IR - Marcenaro A FIR - Marcenaro, Alessandro IR - Marchetti AR FIR - Marchetti, Anna Rosa IR - Mariano C FIR - Mariano, Carlo IR - Marino A FIR - Marino, Antonino IR - Mariuz M FIR - Mariuz, Manuela IR - Maroni A FIR - Maroni, Achille IR - Martori A FIR - Martori, Ampelio IR - Masoch G FIR - Masoch, Gigliola IR - Mattioli M FIR - Mattioli, Mauro IR - Mattioli C FIR - Mattioli, Carlo IR - Maurici V FIR - Maurici, Vincenzo IR - Mauro N FIR - Mauro, Nicola IR - Boscaro F FIR - Boscaro, Federica IR - Bossi P FIR - Bossi, Paolo IR - Bozza G FIR - Bozza, Giulio IR - Bracone E FIR - Bracone, Enrico IR - Brandodoro L FIR - Brandodoro, Lucio IR - Brasesco P FIR - Brasesco, Pierclaudio IR - Breviario A FIR - Breviario, Adele IR - Brizzi A FIR - Brizzi, Antonio IR - Brugnetta M FIR - Brugnetta, Maurizio IR - Bruno G FIR - Bruno, Giuseppe IR - Buemi G FIR - Buemi, Giuseppe IR - Bufano C FIR - Bufano, Carmine IR - Bugli T FIR - Bugli, Tiziano IR - Burigo D FIR - Burigo, Daniela IR - Buzzatti A FIR - Buzzatti, Agostino IR - Caccamo OA FIR - Caccamo, Orazio Antonio IR - Cadamosti D FIR - Cadamosti, Danilo IR - Cagliesi F FIR - Cagliesi, Francesco IR - Caleffa M FIR - Caleffa, Manuela IR - Cammisa N FIR - Cammisa, Nicolo IR - Campo F FIR - Campo, Franceso IR - Campobello M FIR - Campobello, Margherita IR - Caputo S FIR - Caputo, Stanislao IR - Caraccio N FIR - Caraccio, Nicola IR - Cardi S FIR - Cardi, Silvio IR - Cardinale F FIR - Cardinale, Fulvio IR - Frascati A FIR - Frascati, Angelo IR - Frignani P FIR - Frignani, Patrizia IR - Fronteddu PF FIR - Fronteddu, Pier Francesco IR - Gadaleta Caldarola G FIR - Gadaleta Caldarola, Gennaro IR - Gallicchio N FIR - Gallicchio, Nicola IR - Gallina F FIR - Gallina, Franco IR - Gallo S FIR - Gallo, Silvano IR - Gambino F FIR - Gambino, Fortunato IR - Gambuzza G FIR - Gambuzza, Guglielmo IR - Garaffa E FIR - Garaffa, Elio IR - Garagiola A FIR - Garagiola, Alberto IR - Garofalo R FIR - Garofalo, Remigio IR - Garrone A FIR - Garrone, Alfonsino IR - Gatta L FIR - Gatta, Luigi IR - Gennari M FIR - Gennari, Massimo IR - Gerace A FIR - Gerace, Antonio IR - Geremia MA FIR - Geremia, Maria Alessandra IR - Germini F FIR - Germini, Fabrizio IR - Giacci L FIR - Giacci, Luciano IR - Giannini O FIR - Giannini, Olivia IR - Giordano S FIR - Giordano, Stefano IR - Giovannelli U FIR - Giovannelli, Umberto IR - Giuffre G FIR - Giuffre, Giuseppe IR - Giunti G FIR - Giunti, Giuliana IR - Glaviano B FIR - Glaviano, Bruno IR - Gorletta G FIR - Gorletta, Giovanni IR - Grand P FIR - Grand, Paola IR - Grassini G FIR - Grassini, Giovanni IR - Grasso AM FIR - Grasso, Anna Maria IR - Grasso MF FIR - Grasso, Maria Filomena IR - Grasso G FIR - Grasso, Giuseppe IR - Greco A FIR - Greco, Agostino IR - Grifagni M FIR - Grifagni, Marcello IR - Grilli P FIR - Grilli, Piero IR - Grimaldi N FIR - Grimaldi, Nicola IR - Moretti M FIR - Moretti, Marino IR - Morgana I FIR - Morgana, Ignazio IR - Morganti M FIR - Morganti, Mauro IR - Mormile A FIR - Mormile, Annunziata IR - Moro R FIR - Moro, Roberto IR - Mostacciolo F FIR - Mostacciolo, Francesco IR - Mourglia D FIR - Mourglia, Danilo IR - Murari T FIR - Murari, Tiziana IR - Muratore A FIR - Muratore, Alessandro IR - Murgia R FIR - Murgia, Rosalba IR - Naccari M FIR - Naccari, Massimo IR - Napoli L FIR - Napoli, Luigi IR - Nardacci G FIR - Nardacci, Giuseppe IR - La Mattina R FIR - La Mattina, Rosolino IR - La Torre A FIR - La Torre, Angelo IR - Lacava C FIR - Lacava, Cosimo IR - Lalli P FIR - Lalli, Pasqualino IR - Lamera G FIR - Lamera, Giorgio IR - Lanza G FIR - Lanza, Gerardo IR - Lardo G FIR - Lardo, Gerardo IR - Laringe M FIR - Laringe, Matteo IR - Lattanzio G FIR - Lattanzio, Giuseppe IR - Le Foche L FIR - Le Foche, Luca IR - Leo R FIR - Leo, Rosanna IR - Leuzzi G FIR - Leuzzi, Giacomo IR - Lipari F FIR - Lipari, Francesco IR - Lipari A FIR - Lipari, Antonino IR - Lippa L FIR - Lippa, Luciano IR - Lo Conte M FIR - Lo Conte, Maurizio IR - Lo Giudice D FIR - Lo Giudice, Domenico IR - Lonati R FIR - Lonati, Rossella IR - Lorenzina E FIR - Lorenzina, Enrico IR - Magi L FIR - Magi, Lorenzo IR - Magliozzo Francesco F FIR - Magliozzo Francesco, Francesco IR - Mallamo L FIR - Mallamo, Luciano IR - Mazzardi L FIR - Mazzardi, Lidia IR - Mazzarini M FIR - Mazzarini, Massimo IR - Mazzi W FIR - Mazzi, Wainer IR - Mazzocchetti A FIR - Mazzocchetti, Alvaro IR - Mazzoleni F FIR - Mazzoleni, Francesco IR - Mazzorana M FIR - Mazzorana, Michela IR - Medagliani G FIR - Medagliani, Giorgio IR - Medea G FIR - Medea, Gerardo IR - Merlino G FIR - Merlino, Giovanni IR - Merone L FIR - Merone, Laura IR - Metrucci A FIR - Metrucci, Antonio IR - Mezzano S FIR - Mezzano, Silvio IR - Micchi A FIR - Micchi, Alessio IR - Micheli PS FIR - Micheli, Pietro Severo IR - Milazzo V FIR - Milazzo, Vito IR - Minafra F FIR - Minafra, Francesco IR - Minetti L FIR - Minetti, Luca IR - Mirandola C FIR - Mirandola, Cipriano IR - Monari G FIR - Monari, Gianluigi IR - Mongiello C FIR - Mongiello, Claudio IR - Montano G FIR - Montano, Giovanni IR - Montera C FIR - Montera, Carmine IR - Nebiacolombo C FIR - Nebiacolombo, Cristina IR - Negri F FIR - Negri, Fabrizio IR - Nicolini G FIR - Nicolini, Gianfranco IR - Nigro A FIR - Nigro, Antonio IR - Noia E FIR - Noia, Emanuela IR - Nuti CP FIR - Nuti, Claudio Pietro IR - Olivani E FIR - Olivani, Enrico IR - Orlando C FIR - Orlando, Celestina IR - Padovan L FIR - Padovan, Letizia IR - Padula MS FIR - Padula, Maria Stella IR - Pagan M FIR - Pagan, Maurizio IR - Pannacci V FIR - Pannacci, Valerio IR - Pantalone V FIR - Pantalone, Vincenzo IR - Paolini I FIR - Paolini, Italo IR - Papandrea G FIR - Papandrea, Giampaolo IR - Papini G FIR - Papini, Giovanni IR - Papulino F FIR - Papulino, Francesco IR - Paradisi E FIR - Paradisi, Enza IR - Parisi C FIR - Parisi, Carmela IR - Parretti D FIR - Parretti, Damiano IR - Pasculli D FIR - Pasculli, Domenico IR - Pasinelli PC FIR - Pasinelli, Pietro Carlo IR - Pasqualetto S FIR - Pasqualetto, Salvatore IR - Passamonti M FIR - Passamonti, Marco IR - Passaro V FIR - Passaro, Vincenzo IR - Pederzani F FIR - Pederzani, Fabio IR - Pedrazzoli G FIR - Pedrazzoli, Giuliano IR - Pelizzari PC FIR - Pelizzari, Pier Carlo IR - Pernici P FIR - Pernici, Pierrenato IR - Pesaresi C FIR - Pesaresi, Carlo IR - Pesce GL FIR - Pesce, Gian Luigi IR - Petrucci M FIR - Petrucci, Mauro IR - Petrucci M FIR - Petrucci, Marco IR - Petrulli C FIR - Petrulli, Carmela IR - Petti S FIR - Petti, Stefano IR - Piccinocchi G FIR - Piccinocchi, Gaetano IR - Picciotto R FIR - Picciotto, Rinaldo IR - Piccolo F FIR - Piccolo, Francesco IR - Pierobon I FIR - Pierobon, Ivo IR - Pilone R FIR - Pilone, Rita IR - Piva R FIR - Piva, Roberto IR - Pizzillo C FIR - Pizzillo, Carlo IR - Plebani F FIR - Plebani, Franco IR - Polistina S FIR - Polistina, Stefano IR - Pontari A FIR - Pontari, Antonino IR - Poppi MC FIR - Poppi, Maria Cristina IR - Portanti C FIR - Portanti, Carla IR - Prencipe G FIR - Prencipe, Giovanni IR - Prestifilippo A FIR - Prestifilippo, Alessandro IR - Procopio A FIR - Procopio, Antonio IR - Profeta G FIR - Profeta, Gaetano IR - Proietti C FIR - Proietti, Carlo IR - Quattrocchi P FIR - Quattrocchi, Pietro IR - Raciti T FIR - Raciti, Teodoro IR - Ragazzoni A FIR - Ragazzoni, Anna IR - Rattini E FIR - Rattini, Emanuela IR - Reale E FIR - Reale, Emanuela IR - Redaelli D FIR - Redaelli, Dario IR - Reggiani C FIR - Reggiani, Claudio IR - Ricotta G FIR - Ricotta, Giuseppe IR - Rigamonti R FIR - Rigamonti, Rodolfo IR - Righini V FIR - Righini, Velella IR - Rinaldi V FIR - Rinaldi, Vanna IR - Rista P FIR - Rista, Pierangela IR - Romano S FIR - Romano, Salvatore IR - Romei F FIR - Romei, Federico IR - Rossi A FIR - Rossi, Alberto IR - Rossi A FIR - Rossi, Angelo IR - Rossi F FIR - Rossi, Francesco IR - Rossi G FIR - Rossi, Gianluca IR - Rosso L FIR - Rosso, Lucia IR - Rovazzani M FIR - Rovazzani, Massimo IR - Rovelli M FIR - Rovelli, Monica IR - Rovescala P FIR - Rovescala, Pietroclaudio IR - Rubicini G FIR - Rubicini, Giuseppe IR - Rubini S FIR - Rubini, Stefano IR - Russo V FIR - Russo, Vincenzo IR - Russo C FIR - Russo, Carolina IR - Sala M FIR - Sala, Massimo IR - Salurso D FIR - Salurso, Daniele IR - Salvaderi MD FIR - Salvaderi, Maria Dionice IR - Salvato A FIR - Salvato, Alberto IR - Salvetti A FIR - Salvetti, Andrea IR - Salvio G FIR - Salvio, Giuliano IR - Samani F FIR - Samani, Fabio IR - Sammarco R FIR - Sammarco, Renato IR - Santoiemma L FIR - Santoiemma, Luigi IR - Santoro M FIR - Santoro, Michele IR - Sassarini G FIR - Sassarini, Graziano IR - Savino A FIR - Savino, Andrea IR - Scaglione M FIR - Scaglione, Matteo IR - Scarano L FIR - Scarano, Libero IR - Schiavone C FIR - Schiavone, Ciro IR - Scola V FIR - Scola, Vincenzo IR - Scorpiniti A FIR - Scorpiniti, Anna IR - Scotto DA FIR - Scotto, D'Antuono Antonio IR - Scovotto MA FIR - Scovotto, Mari Antonietta IR - Scuri MG FIR - Scuri, Maurizio Giovanni IR - Scuteri A FIR - Scuteri, Antonio IR - Sebastianelli G FIR - Sebastianelli, Giuliano IR - Sebben M FIR - Sebben, Maurizio IR - Sforza P FIR - Sforza, Pasqualino IR - Sfragara I FIR - Sfragara, Ignazio IR - Sicari G FIR - Sicari, Giuseppe IR - Simonini G FIR - Simonini, Giorgio IR - Soldani M FIR - Soldani, Miriam IR - Soverina P FIR - Soverina, Patrizio IR - Spagnolo B FIR - Spagnolo, Beatrice IR - Sperandio M FIR - Sperandio, Massimo IR - Spezzano A FIR - Spezzano, Alfredo IR - Steri L FIR - Steri, Lia IR - Storni P FIR - Storni, Paolo IR - Strada S FIR - Strada, Sonia IR - Stramenga C FIR - Stramenga, Carlo IR - Tagliabue PF FIR - Tagliabue, Paola Fausta IR - Tarabini L FIR - Tarabini, Legnoaura IR - Tarallo N FIR - Tarallo, Nicola IR - Tei A FIR - Tei, Alessandro IR - Tei GP FIR - Tei, Gian Paolo IR - Testi S FIR - Testi, Ser IR - Testolin E FIR - Testolin, Ennio IR - Tibo A FIR - Tibo, Angela IR - Titone N FIR - Titone, Nicolo IR - Tomasello A FIR - Tomasello, Antonino IR - Tondi L FIR - Tondi, Lidia IR - Torti GT FIR - Torti, Giorgio Tommaso IR - Toscano E FIR - Toscano, Emanuele IR - Tota MF FIR - Tota, Maria Fiorenza IR - Tozzoli A FIR - Tozzoli, Alfonso IR - Travaglini R FIR - Travaglini, Rita IR - Trois P FIR - Trois, Paolo IR - Trotta G FIR - Trotta, Gaetano IR - Tuia B FIR - Tuia, Bruno IR - Turbil E FIR - Turbil, Enrico IR - Ughetti C FIR - Ughetti, Claudio IR - Urru C FIR - Urru, Cesare IR - Valente F FIR - Valente, Fabio IR - Valdevit M FIR - Valdevit, Maria IR - Valenti M FIR - Valenti, Marco IR - Valle L FIR - Valle, Lucia IR - Valletta D FIR - Valletta, Domenico IR - Valore S FIR - Valore, Salvatore IR - Varriale A FIR - Varriale, Antonio IR - Varrica G FIR - Varrica, Gaetano IR - Ventriglia G FIR - Ventriglia, Giuseppe IR - Venturelli A FIR - Venturelli, Antonio IR - Vesco G FIR - Vesco, Giuseppe IR - Vezzosi A FIR - Vezzosi, Angelo IR - Viola D FIR - Viola, Dario IR - Viscusi B FIR - Viscusi, Bruno IR - Vita S FIR - Vita, Salvatore IR - Vitali F FIR - Vitali, Franco IR - Vittozzi DS FIR - Vittozzi, Dante Sergio IR - Volpe A FIR - Volpe, Augusto IR - Volpone DA FIR - Volpone, Damiano Antonio IR - Voza I FIR - Voza, Italo IR - Zaninetti P FIR - Zaninetti, Piero IR - Zanini R FIR - Zanini, Riccardo IR - Zennaro W FIR - Zennaro, Walter IR - Zingaro A FIR - Zingaro, Angelo IR - Vivona G FIR - Vivona, Giacomo IR - Zadra A FIR - Zadra, Alessandro IR - Zito A FIR - Zito, Alfonso IR - Zollino L FIR - Zollino, Luciana IR - Zovi MC FIR - Zovi, Maria Carla IR - Zunino R FIR - Zunino, Roberto EDAT- 2012/10/09 06:00 MHDA- 2013/07/31 06:00 CRDT- 2012/10/09 06:00 PHST- 2012/05/16 00:00 [received] PHST- 2012/09/04 00:00 [revised] PHST- 2012/09/13 00:00 [accepted] PHST- 2012/10/09 06:00 [entrez] PHST- 2012/10/09 06:00 [pubmed] PHST- 2013/07/31 06:00 [medline] AID - S0953-6205(12)00248-8 [pii] AID - 10.1016/j.ejim.2012.09.010 [doi] PST - ppublish SO - Eur J Intern Med. 2013 Mar;24(2):161-6. doi: 10.1016/j.ejim.2012.09.010. Epub 2012 Oct 4. PMID- 23258929 OWN - NLM STAT- MEDLINE DCOM- 20130625 LR - 20121221 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 20 IP - 1 DP - 2013 Feb TI - Guidelines on CVD prevention: confusing or complementary? PG - 6-8 LID - 10.1177/2047487312464001 [doi] FAU - De Backer, Guy AU - De Backer G FAU - Catapano, Alberico L AU - Catapano AL FAU - Chapman, John AU - Chapman J FAU - Graham, Ian AU - Graham I FAU - Reiner, Zeljko AU - Reiner Z FAU - Perk, Joep AU - Perk J FAU - Wiklund, Olov AU - Wiklund O LA - eng PT - Editorial PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 SB - IM MH - Cardiovascular Diseases/*prevention & control MH - Humans MH - Practice Guidelines as Topic/*standards EDAT- 2012/12/22 06:00 MHDA- 2013/06/26 06:00 CRDT- 2012/12/22 06:00 PHST- 2012/12/22 06:00 [entrez] PHST- 2012/12/22 06:00 [pubmed] PHST- 2013/06/26 06:00 [medline] AID - 20/1/6 [pii] AID - 10.1177/2047487312464001 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2013 Feb;20(1):6-8. doi: 10.1177/2047487312464001. PMID- 23102598 OWN - NLM STAT- MEDLINE DCOM- 20130528 LR - 20121224 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 226 IP - 1 DP - 2013 Jan TI - Guidelines on CVD prevention: confusing or complementary? PG - 299-300 LID - 10.1016/j.atherosclerosis.2012.10.042 [doi] LID - S0021-9150(12)00726-5 [pii] FAU - De Backer, G AU - De Backer G FAU - Catapano, A L AU - Catapano AL FAU - Chapman, J AU - Chapman J FAU - Graham, I AU - Graham I FAU - Reiner, Z AU - Reiner Z FAU - Perk, J AU - Perk J FAU - Wiklund, O AU - Wiklund O LA - eng PT - Editorial DEP - 20121017 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 SB - IM MH - Cardiovascular Diseases/*prevention & control MH - Humans MH - Practice Guidelines as Topic/standards EDAT- 2012/10/30 06:00 MHDA- 2013/05/29 06:00 CRDT- 2012/10/30 06:00 PHST- 2012/10/10 00:00 [received] PHST- 2012/10/10 00:00 [accepted] PHST- 2012/10/30 06:00 [entrez] PHST- 2012/10/30 06:00 [pubmed] PHST- 2013/05/29 06:00 [medline] AID - S0021-9150(12)00726-5 [pii] AID - 10.1016/j.atherosclerosis.2012.10.042 [doi] PST - ppublish SO - Atherosclerosis. 2013 Jan;226(1):299-300. doi: 10.1016/j.atherosclerosis.2012.10.042. Epub 2012 Oct 17. PMID- 23428644 OWN - NLM STAT- MEDLINE DCOM- 20130819 LR - 20151119 IS - 1421-9751 (Electronic) IS - 0008-6312 (Linking) VI - 124 IP - 2 DP - 2013 TI - High-density lipoprotein subfractions--what the clinicians need to know. PG - 116-25 LID - 10.1159/000346463 [doi] AB - Although the inverse relationship between plasma levels of high-density lipoprotein (HDL) and cardiovascular disease has been largely demonstrated, many observations have suggested that the assessment of HDL functionality might be more informative than a simple measurement of HDL-cholesterol plasma levels. HDLs are a class of structurally and functionally heterogeneous particles; in atherosclerosis-related diseases, changes in HDL subfraction levels and functions are frequently observed. Circulating levels of large HDL particles are decreased in dyslipidaemic conditions, while levels of small dense HDL particles are increased in patients with coronary heart disease. Furthermore, specific genetic defects in proteins involved in HDL metabolism significantly impact the distribution of HDL subpopulations. Finally, many drugs used for dyslipidaemia induce changes in HDL subfractions strictly related to cardiovascular disease. Although several methods exist to evaluate HDL subclass levels, most of them are not easily applicable in clinical practice, due to the costs and high variability. However, the possibility to measure the levels of specific HDL subfractions in patients with atherosclerosis-related diseases might help to better define their cardiovascular risk. CI - Copyright (c) 2013 S. Karger AG, Basel. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20130220 PL - Switzerland TA - Cardiology JT - Cardiology JID - 1266406 RN - 0 (Apolipoproteins) RN - 0 (Cholesterol Ester Transfer Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fibric Acids) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoproteins, HDL) RN - 2679MF687A (Niacin) SB - IM CIN - Cardiology. 2013;126(2):96. PMID: 23948795 MH - Apolipoproteins/metabolism MH - Cardiovascular Diseases/*blood/drug therapy/genetics MH - Cholesterol Ester Transfer Proteins/antagonists & inhibitors MH - Enzyme Inhibitors/therapeutic use MH - Fatty Acids, Omega-3/administration & dosage MH - Fibric Acids/therapeutic use MH - Humans MH - Hypolipidemic Agents/therapeutic use MH - Lipoproteins, HDL/classification/*metabolism/physiology MH - Liver/metabolism MH - Mutation/genetics MH - Niacin/therapeutic use EDAT- 2013/02/23 06:00 MHDA- 2013/08/21 06:00 CRDT- 2013/02/23 06:00 PHST- 2012/09/25 00:00 [received] PHST- 2012/12/06 00:00 [accepted] PHST- 2013/02/23 06:00 [entrez] PHST- 2013/02/23 06:00 [pubmed] PHST- 2013/08/21 06:00 [medline] AID - 000346463 [pii] AID - 10.1159/000346463 [doi] PST - ppublish SO - Cardiology. 2013;124(2):116-25. doi: 10.1159/000346463. Epub 2013 Feb 20. PMID- 23286439 OWN - NLM STAT- MEDLINE DCOM- 20131210 LR - 20180605 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 19 IP - 21 DP - 2013 TI - Achieving current goals in prevention and treatment of vascular disease: an update. PG - 3749-52 FAU - Catapano, Alberico L AU - Catapano AL FAU - Elisaf, Moses S AU - Elisaf MS FAU - Florentin, Matilda AU - Florentin M FAU - Mikhailidis, Dimitri P AU - Mikhailidis DP FAU - Kostapanos, Michael S AU - Kostapanos MS LA - eng PT - Editorial PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Cardiovascular Agents) SB - IM MH - Animals MH - Cardiovascular Agents/adverse effects/pharmacology/*therapeutic use MH - Cardiovascular Diseases/*drug therapy/etiology/prevention & control MH - Drug Design MH - Humans MH - Risk Factors EDAT- 2013/01/05 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/01/05 06:00 PHST- 2013/01/05 06:00 [entrez] PHST- 2013/01/05 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - CPD-EPUB-20121226-21 [pii] PST - ppublish SO - Curr Pharm Des. 2013;19(21):3749-52. PMID- 23286430 OWN - NLM STAT- MEDLINE DCOM- 20131210 LR - 20180605 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 19 IP - 21 DP - 2013 TI - Treating high density lipoprotein cholesterol (HDL-C): quantity versus quality. PG - 3841-57 AB - Low density lipoproteins (LDL) and high density lipoproteins (HDL) are independent risk factors for coronary heart disease (CHD); decreasing LDL-cholesterol (LDL-C) levels with statin therapy represents the primary goal in the management of cardiovascular disease. However, despite the efficacy of statins in reducing cardiovascular morbidity and mortality, a significant residual risk has been observed even after reaching the LDL-C target, suggesting that other risk factors beyond LDL-C should be addressed, including low levels of HDL-cholesterol (HDL-C). Several clinical trials have shown an inverse relationship between HDL-C levels and cardiovascular risk, and 1 mg/dl increment in HDL-C is associated in epidemiological studies with a 2-3% decrease in cardiovascular risk, suggesting that raising HDL-C levels might have beneficial effects to reduce cardiovascular disease. However, several lines of evidence indicate that the functional properties of HDL may be relevant as well. In patient with CAD and normal HDL-C levels, HDL exhibit significantly reduced protective functions, and rather appear to be pro-atherogenic; on the other hand some genetic mutations causing low levels of HDL-C are not associated with increased atherosclerosis. Furthermore, although niacin significantly increased HDL-C levels, no further clinical benefit was observed from the addition of niacin to statin therapy, suggesting that increasing HDL-C levels is not sufficient and perhaps functional properties of HDL must be considered when choosing a therapeutic strategy to reduce the residual cardiovascular risk. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. angela.pirillo@guest.unimi.it FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 2679MF687A (Niacin) SB - IM MH - Animals MH - Cardiovascular Diseases/etiology/*prevention & control MH - Cholesterol, HDL/blood/*drug effects MH - Cholesterol, LDL/blood/*drug effects MH - Clinical Trials as Topic MH - Coronary Disease/etiology/prevention & control MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/pharmacology/therapeutic use MH - Niacin/administration & dosage/pharmacology/therapeutic use MH - Risk Factors EDAT- 2013/01/05 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/01/05 06:00 PHST- 2012/12/16 00:00 [received] PHST- 2012/12/25 00:00 [accepted] PHST- 2013/01/05 06:00 [entrez] PHST- 2013/01/05 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - CPD-EPUB-20121226-12 [pii] PST - ppublish SO - Curr Pharm Des. 2013;19(21):3841-57. PMID- 24198442 OWN - NLM STAT- MEDLINE DCOM- 20140620 LR - 20181113 IS - 1875-8630 (Electronic) IS - 0278-0240 (Linking) VI - 35 IP - 5 DP - 2013 TI - Soluble lectin-like oxidized low density lipoprotein receptor-1 as a biochemical marker for atherosclerosis-related diseases. PG - 413-8 LID - 10.1155/2013/716325 [doi] AB - Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), the main oxidized low-density lipoprotein (OxLDL) in endothelial cells, is upregulated in atherosclerotic lesions and is involved in several cellular processes that regulate the pathogenesis of atherosclerosis. The LOX-1 expressed on the cell surface can be proteolytically cleaved and released in a soluble form (sLOX-1) in the circulation under pathological conditions. Serum levels of sLOX-1, in fact, are elevated at the early stages of acute coronary syndrome and are associated with coronary plaque vulnerability and with the presence of multiple complex coronary lesions. Moreover, in subjects with stable CAD, levels of serum sLOX-1 are associated with the presence of lesions in the proximal and mid-segments of the left anterior descending artery that are the most prone to rupture; in subjects undergoing percutaneous coronary intervention, baseline preprocedural serum sLOX-1 levels are associated with the incidence of periprocedural myocardial infarction. Altogether, these findings suggest that circulating levels of sLOX-1 might be a diagnostic and prognostic marker for atherosclerotic-related events. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Via Gorki 50, Cinisello Balsamo, 20092, Italy ; IRCCS MultiMedica, Via San Barnaba 29, 20162 Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20130930 PL - United States TA - Dis Markers JT - Disease markers JID - 8604127 RN - 0 (Biomarkers) RN - 0 (OLR1 protein, human) RN - 0 (Scavenger Receptors, Class E) SB - IM MH - Acute Coronary Syndrome/blood/*diagnosis MH - Atherosclerosis/blood/*diagnosis MH - Biomarkers/blood/metabolism MH - Coronary Artery Disease/blood/*diagnosis MH - Humans MH - Metabolic Diseases/blood/*diagnosis MH - Scavenger Receptors, Class E/*blood/metabolism PMC - PMC3809739 EDAT- 2013/11/08 06:00 MHDA- 2014/06/21 06:00 CRDT- 2013/11/08 06:00 PHST- 2013/06/27 00:00 [received] PHST- 2013/08/26 00:00 [accepted] PHST- 2013/11/08 06:00 [entrez] PHST- 2013/11/08 06:00 [pubmed] PHST- 2014/06/21 06:00 [medline] AID - 10.1155/2013/716325 [doi] PST - ppublish SO - Dis Markers. 2013;35(5):413-8. doi: 10.1155/2013/716325. Epub 2013 Sep 30. PMID- 23935243 OWN - NLM STAT- MEDLINE DCOM- 20140226 LR - 20181113 IS - 1466-1861 (Electronic) IS - 0962-9351 (Linking) VI - 2013 DP - 2013 TI - LOX-1, OxLDL, and atherosclerosis. PG - 152786 LID - 10.1155/2013/152786 [doi] AB - Oxidized low-density lipoprotein (OxLDL) contributes to the atherosclerotic plaque formation and progression by several mechanisms, including the induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation. Vascular wall cells express on their surface several scavenger receptors that mediate the cellular effects of OxLDL. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main OxLDL receptor of endothelial cells, and it is expressed also in macrophages and smooth muscle cells. LOX-1 is almost undetectable under physiological conditions, but it is upregulated following the exposure to several proinflammatory and proatherogenic stimuli and can be detected in animal and human atherosclerotic lesions. The key contribution of LOX-1 to the atherogenic process has been confirmed in animal models; LOX-1 knockout mice exhibit reduced intima thickness and inflammation and increased expression of protective factors; on the contrary, LOX-1 overexpressing mice present an accelerated atherosclerotic lesion formation which is associated with increased inflammation. In humans, LOX-1 gene polymorphisms were associated with increased susceptibility to myocardial infarction. Inhibition of the LOX-1 receptor with chemicals or antisense nucleotides is currently being investigated and represents an emerging approach for controlling OxLDL-LOX-1 mediated proatherogenic effects. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, 20092 Cinisello Balsamo, Italy. angela.pirillo@guest.unimi.it FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20130710 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Ligands) RN - 0 (Lipoproteins, LDL) RN - 0 (OLR1 protein, human) RN - 0 (Scavenger Receptors, Class E) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Animals MH - Apoptosis MH - Atherosclerosis/genetics/*pathology MH - Endothelial Cells/cytology MH - Endothelium, Vascular/pathology MH - Humans MH - Inflammation MH - Ligands MH - Lipoproteins, LDL/*metabolism MH - Macrophages/cytology/metabolism MH - Mice MH - Mice, Knockout MH - Myocardial Infarction/pathology MH - Myocytes, Smooth Muscle/cytology MH - Platelet Activation MH - Reperfusion Injury/pathology MH - Scavenger Receptors, Class E/*metabolism PMC - PMC3723318 EDAT- 2013/08/13 06:00 MHDA- 2014/02/27 06:00 CRDT- 2013/08/13 06:00 PHST- 2013/04/30 00:00 [received] PHST- 2013/06/16 00:00 [accepted] PHST- 2013/08/13 06:00 [entrez] PHST- 2013/08/13 06:00 [pubmed] PHST- 2014/02/27 06:00 [medline] AID - 10.1155/2013/152786 [doi] PST - ppublish SO - Mediators Inflamm. 2013;2013:152786. doi: 10.1155/2013/152786. Epub 2013 Jul 10. PMID- 23690668 OWN - NLM STAT- MEDLINE DCOM- 20131203 LR - 20181113 IS - 1466-1861 (Electronic) IS - 0962-9351 (Linking) VI - 2013 DP - 2013 TI - Long pentraxin 3: experimental and clinical relevance in cardiovascular diseases. PG - 725102 LID - 10.1155/2013/725102 [doi] AB - Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and belongs, together with the C-reactive protein (CRP) and other acute phase proteins, to the pentraxins' superfamily: soluble, multifunctional, pattern recognition proteins. Pentraxins share a common C-terminal pentraxin domain, which in the case of PTX3 is coupled to an unrelated long N-terminal domain. PTX3 in humans, like CRP, correlates with surrogate markers of atherosclerosis and is independently associated with the risk of developing vascular events. Studies addressing the potential physiopathological role of CRP in the cardiovascular system were so far inconclusive and have been limited by the fact that the sequence and regulation have not been conserved during evolution between mouse and man. On the contrary, the conservation of sequence, gene organization, and regulation of PTX3 supports the translation of animal model findings in humans. While PTX3 deficiency is associated with increased inflammation, cardiac damage, and atherosclerosis, the overexpression limits carotid restenosis after angioplasty. These observations point to a cardiovascular protective effect of PTX3 potentially associated with the ability of tuning inflammation and favor the hypothesis that the increased levels of PTX3 in subjects with cardiovascular diseases may reflect a protective physiological mechanism, which correlates with the immunoinflammatory response observed in several cardiovascular disorders. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita Degli Studi di Milano, 20133 Milan, Italy. FAU - Baragetti, Andrea AU - Baragetti A FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130407 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Serum Amyloid P-Component) RN - 148591-49-5 (PTX3 protein) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Animals MH - C-Reactive Protein/genetics/*metabolism MH - Cardiovascular Diseases/genetics/*metabolism MH - Humans MH - Inflammation/genetics/metabolism MH - Serum Amyloid P-Component/genetics/*metabolism PMC - PMC3649691 EDAT- 2013/05/22 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/05/22 06:00 PHST- 2012/12/21 00:00 [received] PHST- 2013/02/27 00:00 [accepted] PHST- 2013/05/22 06:00 [entrez] PHST- 2013/05/22 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - 10.1155/2013/725102 [doi] PST - ppublish SO - Mediators Inflamm. 2013;2013:725102. doi: 10.1155/2013/725102. Epub 2013 Apr 7. PMID- 23320105 OWN - NLM STAT- MEDLINE DCOM- 20130815 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - Class II phosphoinositide 3-kinases contribute to endothelial cells morphogenesis. PG - e53808 LID - 10.1371/journal.pone.0053808 [doi] AB - The question of whether the distinct isoforms of the family of enzymes phosphoinositide 3-kinases (PI3Ks) play redundant roles within a cell or whether they control distinct cellular processes or distinct steps within the same cellular process has gained considerable importance in the recent years due to the development of inhibitors able to selectively target individual isoforms. It is important to understand whether inhibition of one PI3K can result in compensatory effect from other isoform(s) and therefore whether strategies aimed at simultaneously blocking more than one PI3K may be needed. In this study we investigated the relative contribution of distinct PI3K isoforms to endothelial cells (EC) functions specifically regulated by the sphingolipid sphingosine-1-phosphate (S1P) and by high density lipoproteins (HDL), the major carrier of S1P in human plasma. Here we show that a co-ordinated action of different PI3Ks is required to tightly regulate remodelling of EC on Matrigel, a process dependent on cell proliferation, apoptosis and migration. The contribution of each isoform to this process appears to be distinct, with the class II enzyme PI3K-C2beta and the class IB isoform p110gamma mainly regulating the S1P- and HDL-dependent EC migration and PI3K-C2alpha primarily controlling EC survival. Data further indicate that PI3K-C2beta and p110gamma control distinct steps involved in cell migration supporting the hypothesis that different PI3Ks regulate distinct cellular processes. FAU - Tibolla, Gianpaolo AU - Tibolla G AD - Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, Centre for Diabetes, Inositide Signalling Group, London, United Kingdom. FAU - Pineiro, Roberto AU - Pineiro R FAU - Chiozzotto, Daniela AU - Chiozzotto D FAU - Mavrommati, Ioanna AU - Mavrommati I FAU - Wheeler, Ann P AU - Wheeler AP FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Maffucci, Tania AU - Maffucci T FAU - Falasca, Marco AU - Falasca M LA - eng GR - 09/0003971/Diabetes UK/United Kingdom GR - PG/04/033/16906/British Heart Foundation/United Kingdom GR - PG/06/022/20348/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130108 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Isoenzymes) RN - 0 (Lysophospholipids) RN - 26993-30-6 (sphingosine 1-phosphate) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (Class II Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (PIK3C2A protein, human) RN - EC 2.7.1.137 (PIK3C2B protein, human) RN - NGZ37HRE42 (Sphingosine) SB - IM MH - Apoptosis/drug effects/physiology MH - Cell Movement/drug effects/physiology MH - Cell Proliferation/drug effects MH - Class II Phosphatidylinositol 3-Kinases MH - Endothelial Cells/*cytology/drug effects/*enzymology MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Isoenzymes/metabolism MH - Lysophospholipids/metabolism MH - Morphogenesis/drug effects/physiology MH - Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/*metabolism MH - Sphingosine/analogs & derivatives/metabolism PMC - PMC3539993 EDAT- 2013/01/16 06:00 MHDA- 2013/08/16 06:00 CRDT- 2013/01/16 06:00 PHST- 2012/05/18 00:00 [received] PHST- 2012/12/04 00:00 [accepted] PHST- 2013/01/16 06:00 [entrez] PHST- 2013/01/16 06:00 [pubmed] PHST- 2013/08/16 06:00 [medline] AID - 10.1371/journal.pone.0053808 [doi] AID - PONE-D-12-14332 [pii] PST - ppublish SO - PLoS One. 2013;8(1):e53808. doi: 10.1371/journal.pone.0053808. Epub 2013 Jan 8. PMID- 23212297 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121206 LR - 20181113 IS - 2162-2531 (Electronic) VI - 1 DP - 2012 Dec 4 TI - LOX-1 Inhibition in ApoE KO Mice Using a Schizophyllan-based Antisense Oligonucleotide Therapy. PG - e58 LID - 10.1038/mtna.2012.45 [doi] FAU - Amati, Francesca AU - Amati F AD - Dipartimento di Biomedicina e Prevenzione, Universita Tor Vergata, Rome, Italy. FAU - Diano, Laura AU - Diano L FAU - Vecchione, Lucia AU - Vecchione L FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Koyama, Yoshikazu AU - Koyama Y FAU - Cutuli, Lucia AU - Cutuli L FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Romeo, Francesco AU - Romeo F FAU - Ando, Hironori AU - Ando H FAU - Novelli, Giuseppe AU - Novelli G LA - eng PT - Journal Article DEP - 20121204 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC3528301 EDAT- 2012/12/06 06:00 MHDA- 2012/12/06 06:01 CRDT- 2012/12/06 06:00 PHST- 2012/12/06 06:00 [entrez] PHST- 2012/12/06 06:00 [pubmed] PHST- 2012/12/06 06:01 [medline] AID - mtna201245 [pii] AID - 10.1038/mtna.2012.45 [doi] PST - epublish SO - Mol Ther Nucleic Acids. 2012 Dec 4;1:e58. doi: 10.1038/mtna.2012.45. PMID- 23341845 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20130124 LR - 20181113 IS - 1671-5411 (Print) IS - 1671-5411 (Linking) VI - 9 IP - 4 DP - 2012 Dec TI - High density lipoproteins and atherosclerosis: emerging aspects. PG - 401-7 LID - 10.3724/SP.J.1263.2011.12282 [doi] AB - High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes. Furthermore, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis. FAU - Sala, Federica AU - Sala F AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan 20133, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Journal Article PL - China TA - J Geriatr Cardiol JT - Journal of geriatric cardiology : JGC JID - 101237881 PMC - PMC3545258 OTO - NOTNLM OT - Apolipoprotein OT - High density lipoproteins OT - Immune response OT - Sphingosine-1-phosphate EDAT- 2013/01/24 06:00 MHDA- 2013/01/24 06:01 CRDT- 2013/01/24 06:00 PHST- 2011/12/28 00:00 [received] PHST- 2012/06/04 00:00 [revised] PHST- 2012/10/22 00:00 [accepted] PHST- 2013/01/24 06:00 [entrez] PHST- 2013/01/24 06:00 [pubmed] PHST- 2013/01/24 06:01 [medline] AID - 10.3724/SP.J.1263.2011.12282 [doi] AID - jgc-09-04-401 [pii] PST - ppublish SO - J Geriatr Cardiol. 2012 Dec;9(4):401-7. doi: 10.3724/SP.J.1263.2011.12282. PMID- 23073138 OWN - NLM STAT- MEDLINE DCOM- 20130326 LR - 20121119 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 428 IP - 2 DP - 2012 Nov 16 TI - Upregulation of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) expression in human endothelial cells by modified high density lipoproteins. PG - 230-3 LID - 10.1016/j.bbrc.2012.10.020 [doi] LID - S0006-291X(12)01957-2 [pii] AB - Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is the main endothelial receptor for oxidized low density lipoprotein (OxLDL). LOX-1 is highly expressed in endothelial cells of atherosclerotic lesions, but also in macrophages and smooth muscle cells. LOX-1 expression is upregulated by several inflammatory cytokines (such as TNF-alpha), by oxidative stress, and by pathological conditions, such as dyslipidemia, hypertension, and diabetes. High density lipoprotein (HDL) possess several atheroprotective properties; however under pathological conditions associated with inflammation and oxidative stress, HDL become dysfunctional and exhibit pro-inflammatory properties. In vitro, HDL can be modified by 15-lipoxygenase, an enzyme overexpressed in the atherosclerotic lesions. Here we report that, after modification with 15-lipoxygenase, HDL(3) lose their ability to inhibit TNFalpha-induced LOX-1 expression in endothelial cells; in addition, 15LO-modified HDL(3) induce LOX-1 mRNA and protein expression and bind to LOX-1 with increased affinity compared to native HDL(3). Altogether these findings confirm that 15LO-modified HDL(3) possess a pro-atherogenic role. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. angela.pirillo@guest.unimi.it FAU - Uboldi, Patrizia AU - Uboldi P FAU - Ferri, Nicola AU - Ferri N FAU - Corsini, Alberto AU - Corsini A FAU - Kuhn, Hartmut AU - Kuhn H FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121013 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Lipoproteins, HDL3) RN - 0 (OLR1 protein, human) RN - 0 (Scavenger Receptors, Class E) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) SB - IM MH - Arachidonate 15-Lipoxygenase/chemistry/*metabolism MH - Cells, Cultured MH - Endothelium, Vascular/*metabolism MH - Humans MH - Lipoproteins, HDL3/chemistry/metabolism MH - Scavenger Receptors, Class E/*biosynthesis MH - Up-Regulation EDAT- 2012/10/18 06:00 MHDA- 2013/03/27 06:00 CRDT- 2012/10/18 06:00 PHST- 2012/10/02 00:00 [received] PHST- 2012/10/03 00:00 [accepted] PHST- 2012/10/18 06:00 [entrez] PHST- 2012/10/18 06:00 [pubmed] PHST- 2013/03/27 06:00 [medline] AID - S0006-291X(12)01957-2 [pii] AID - 10.1016/j.bbrc.2012.10.020 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Nov 16;428(2):230-3. doi: 10.1016/j.bbrc.2012.10.020. Epub 2012 Oct 13. PMID- 22963985 OWN - NLM STAT- MEDLINE DCOM- 20130411 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 225 IP - 1 DP - 2012 Nov TI - HDL and adaptive immunity: a tale of lipid rafts. PG - 34-5 LID - 10.1016/j.atherosclerosis.2012.08.020 [doi] LID - S0021-9150(12)00569-2 [pii] FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. Danilo.Norata@unimi.it FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Comment DEP - 20120823 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoprotein A-I) RN - 0 (Lipoproteins, HDL) SB - IM CON - Atherosclerosis. 2012 Nov;225(1):105-14. PMID: 22862966 MH - Animals MH - Antigen Presentation/*drug effects MH - Antigen-Presenting Cells/*physiology MH - Apolipoprotein A-I/*pharmacology MH - Lipoproteins, HDL/*pharmacology MH - Membrane Microdomains/*drug effects MH - T-Lymphocytes/*physiology EDAT- 2012/09/12 06:00 MHDA- 2013/04/12 06:00 CRDT- 2012/09/12 06:00 PHST- 2012/08/10 00:00 [received] PHST- 2012/08/13 00:00 [accepted] PHST- 2012/09/12 06:00 [entrez] PHST- 2012/09/12 06:00 [pubmed] PHST- 2013/04/12 06:00 [medline] AID - S0021-9150(12)00569-2 [pii] AID - 10.1016/j.atherosclerosis.2012.08.020 [doi] PST - ppublish SO - Atherosclerosis. 2012 Nov;225(1):34-5. doi: 10.1016/j.atherosclerosis.2012.08.020. Epub 2012 Aug 23. PMID- 23096582 OWN - NLM STAT- MEDLINE DCOM- 20130301 LR - 20141120 IS - 1827-6806 (Print) IS - 1827-6806 (Linking) VI - 13 IP - 11 DP - 2012 Nov TI - [Pharmacological prevention of coronary relapses in Italian clinical practice: a literature review]. PG - 734-40 LID - 10.1714/1168.12949 [doi] AB - Scientific advances in cardiovascular research during the last decades have afforded effective pharmacological treatment to those surviving their first acute myocardial infarction. This secondary prevention treatment, based upon the combined administration of statins, aspirin, beta-blockers and renin-angiotensin blockers, might avert great part of the relapses contributing substantially to the overall incidence of acute coronary syndromes in the general population. However, a treatment gap separates evidence-based recommendations from their daily clinical application, a condition frequently explored even in the Italian medical setting. However, a general overview of the problem is missing insofar, a contribution that might eventually help to improve the status of secondary coronary prevention in our national environment. FAU - Pedrinelli, Roberto AU - Pedrinelli R AD - Dipartimento Cardio Toracio e Vascolare, Universita degli Studi, Pisa. r.pedrinelli@med.unipi.it FAU - Ciccone, Marco AU - Ciccone M FAU - Novo, Salvatore AU - Novo S FAU - Catapano, Alberico L AU - Catapano AL LA - ita PT - English Abstract PT - Journal Article PT - Review TT - La prevenzione farmacologica delle recidive coronariche nella pratica clinica italiana: una revisione della letteratura. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Platelet Aggregation Inhibitors) SB - IM MH - Adrenergic beta-Antagonists/*therapeutic use MH - Angiotensin-Converting Enzyme Inhibitors/*therapeutic use MH - Drug Therapy, Combination MH - Evidence-Based Medicine MH - Follow-Up Studies MH - Guideline Adherence MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Italy MH - Myocardial Infarction/drug therapy/*prevention & control MH - Patient Discharge MH - Platelet Aggregation Inhibitors/*therapeutic use MH - Practice Guidelines as Topic MH - Prognosis MH - Quality of Life MH - Risk Assessment MH - Risk Factors MH - Secondary Prevention MH - Treatment Outcome EDAT- 2012/10/26 06:00 MHDA- 2013/03/02 06:00 CRDT- 2012/10/26 06:00 PHST- 2012/10/26 06:00 [entrez] PHST- 2012/10/26 06:00 [pubmed] PHST- 2013/03/02 06:00 [medline] AID - 10.1714/1168.12949 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2012 Nov;13(11):734-40. doi: 10.1714/1168.12949. PMID- 22553931 OWN - NLM STAT- MEDLINE DCOM- 20130418 LR - 20131121 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 14 IP - 10 DP - 2012 Oct TI - Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial. PG - 893-900 LID - 10.1111/j.1463-1326.2012.01615.x [doi] AB - AIM: This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus. METHODS: A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study. RESULTS: After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and beta-cell function. CONCLUSION: Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT. CI - (c) 2012 Blackwell Publishing Ltd. FAU - Monti, L D AU - Monti LD AD - Metabolic and Cardiovascular Science Division, Department of Internal Medicine, San Raffaele Scientific Institute, Milan, Italy. monti.lucilla@hsr.it FAU - Setola, E AU - Setola E FAU - Lucotti, P C G AU - Lucotti PC FAU - Marrocco-Trischitta, M M AU - Marrocco-Trischitta MM FAU - Comola, M AU - Comola M FAU - Galluccio, E AU - Galluccio E FAU - Poggi, A AU - Poggi A FAU - Mammi, S AU - Mammi S FAU - Catapano, A L AU - Catapano AL FAU - Comi, G AU - Comi G FAU - Chiesa, R AU - Chiesa R FAU - Bosi, E AU - Bosi E FAU - Piatti, P M AU - Piatti PM LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20120521 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 94ZLA3W45F (Arginine) SB - IM MH - Administration, Oral MH - Arginine/*administration & dosage/*pharmacology MH - Blood Glucose/*drug effects/metabolism MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - *Dietary Supplements MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Glucose Intolerance/blood/*drug therapy MH - Glucose Tolerance Test MH - Humans MH - Incidence MH - Male MH - Middle Aged MH - Risk Reduction Behavior MH - Time Factors EDAT- 2012/05/05 06:00 MHDA- 2013/04/20 06:00 CRDT- 2012/05/05 06:00 PHST- 2012/05/05 06:00 [entrez] PHST- 2012/05/05 06:00 [pubmed] PHST- 2013/04/20 06:00 [medline] AID - 10.1111/j.1463-1326.2012.01615.x [doi] PST - ppublish SO - Diabetes Obes Metab. 2012 Oct;14(10):893-900. doi: 10.1111/j.1463-1326.2012.01615.x. Epub 2012 May 21. PMID- 22560329 OWN - NLM STAT- MEDLINE DCOM- 20130116 LR - 20181201 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 224 IP - 1 DP - 2012 Sep TI - Leonurine: a new comer in the natural compounds affecting atherosclerosis. PG - 37-8 LID - 10.1016/j.atherosclerosis.2012.02.036 [doi] FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Comment DEP - 20120307 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 09Q5W34QDA (leonurine) RN - 632XD903SP (Gallic Acid) SB - IM CON - Atherosclerosis. 2012 Sep;224(1):43-50. PMID: 22840690 MH - Animals MH - Anti-Inflammatory Agents/*therapeutic use MH - Antioxidants/*therapeutic use MH - Atherosclerosis/*prevention & control MH - Gallic Acid/*analogs & derivatives/therapeutic use MH - Male EDAT- 2012/05/09 06:00 MHDA- 2013/01/17 06:00 CRDT- 2012/05/08 06:00 PHST- 2012/02/15 00:00 [received] PHST- 2012/02/21 00:00 [accepted] PHST- 2012/05/08 06:00 [entrez] PHST- 2012/05/09 06:00 [pubmed] PHST- 2013/01/17 06:00 [medline] AID - S0021-9150(12)00150-5 [pii] AID - 10.1016/j.atherosclerosis.2012.02.036 [doi] PST - ppublish SO - Atherosclerosis. 2012 Sep;224(1):37-8. doi: 10.1016/j.atherosclerosis.2012.02.036. Epub 2012 Mar 7. PMID- 22541275 OWN - NLM STAT- MEDLINE DCOM- 20120717 LR - 20181113 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 379 IP - 9831 DP - 2012 Jun 2 TI - Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. PG - 2053-62 LID - 10.1016/S0140-6736(12)60441-3 [doi] AB - BACKGROUND: Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association. METHODS: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. FINDINGS: Of 21 eligible studies, 16 with 36,984 participants were included. During a mean follow-up of 7.0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0.97 (95% CI 0.94-1.00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0.98 (0.95-1.01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1.16, 95% CI 1.10-1.22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0.06 and r=-0.02). INTERPRETATION: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials. FUNDING: Deutsche Forschungsgemeinschaft. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Lorenz, Matthias W AU - Lorenz MW AD - Department of Neurology, University Hospital, J W Goethe-University, Frankfurt am Main, Germany. matthias.lorenz@em.uni-frankfurt.de FAU - Polak, Joseph F AU - Polak JF FAU - Kavousi, Maryam AU - Kavousi M FAU - Mathiesen, Ellisiv B AU - Mathiesen EB FAU - Volzke, Henry AU - Volzke H FAU - Tuomainen, Tomi-Pekka AU - Tuomainen TP FAU - Sander, Dirk AU - Sander D FAU - Plichart, Matthieu AU - Plichart M FAU - Catapano, Alberico L AU - Catapano AL FAU - Robertson, Christine M AU - Robertson CM FAU - Kiechl, Stefan AU - Kiechl S FAU - Rundek, Tatjana AU - Rundek T FAU - Desvarieux, Moise AU - Desvarieux M FAU - Lind, Lars AU - Lind L FAU - Schmid, Caroline AU - Schmid C FAU - DasMahapatra, Pronabesh AU - DasMahapatra P FAU - Gao, Lu AU - Gao L FAU - Ziegelbauer, Kathrin AU - Ziegelbauer K FAU - Bots, Michiel L AU - Bots ML FAU - Thompson, Simon G AU - Thompson SG CN - PROG-IMT Study Group LA - eng GR - HHSN268201100012C/HL/NHLBI NIH HHS/United States GR - HHSN268201100010C/HL/NHLBI NIH HHS/United States GR - R01 AG015928/AG/NIA NIH HHS/United States GR - HHSN268201100008C/HL/NHLBI NIH HHS/United States GR - U01 HL080295/HL/NHLBI NIH HHS/United States GR - N01-HC-85081/HC/NHLBI NIH HHS/United States GR - R01 DE013094/DE/NIDCR NIH HHS/United States GR - HHSN268201100007C/HL/NHLBI NIH HHS/United States GR - HHSN268200800007C/HL/NHLBI NIH HHS/United States GR - N01 HC015103/HC/NHLBI NIH HHS/United States GR - RG/08/014/24067/British Heart Foundation/United Kingdom GR - R56 AG020098/AG/NIA NIH HHS/United States GR - HHSN268201100011C/HL/NHLBI NIH HHS/United States GR - N01 HC085085/HC/NHLBI NIH HHS/United States GR - N01 HC015103/HC/WHI NIH HHS/United States GR - AG-20098/AG/NIA NIH HHS/United States GR - N01HC55222/HL/NHLBI NIH HHS/United States GR - N01-HC-85086/HC/NHLBI NIH HHS/United States GR - N01HC85086/HL/NHLBI NIH HHS/United States GR - R37 NS029993/NS/NINDS NIH HHS/United States GR - AG-027058/AG/NIA NIH HHS/United States GR - N01-HC-85082/HC/NHLBI NIH HHS/United States GR - HHSN268201100006C/HL/NHLBI NIH HHS/United States GR - N01 HC-55222/HC/NHLBI NIH HHS/United States GR - HHSN268201200036C/HL/NHLBI NIH HHS/United States GR - R37 NS 029993/NS/NINDS NIH HHS/United States GR - N01-HC-85083/HC/NHLBI NIH HHS/United States GR - N01-HC-75150/HC/NHLBI NIH HHS/United States GR - N01-HC-85080/HC/NHLBI NIH HHS/United States GR - R01 HL080295/HL/NHLBI NIH HHS/United States GR - N01 HC045133/HC/WHI NIH HHS/United States GR - N01 HC085084/HC/NHLBI NIH HHS/United States GR - R01 AG020098/AG/NIA NIH HHS/United States GR - N01HC85082/HL/NHLBI NIH HHS/United States GR - N01HC75150/HL/NHLBI NIH HHS/United States GR - HHSN268201100009C/HL/NHLBI NIH HHS/United States GR - N01HC85083/HL/NHLBI NIH HHS/United States GR - HHSN268201100005C/HL/NHLBI NIH HHS/United States GR - MC_U105260792/Medical Research Council/United Kingdom GR - N01-HC-85079/HC/NHLBI NIH HHS/United States GR - HHSN268201200036C/PHS HHS/United States GR - HL080295/HL/NHLBI NIH HHS/United States GR - N01-HC-85239/HC/NHLBI NIH HHS/United States GR - AG-023629/AG/NIA NIH HHS/United States GR - N01HC85079/HL/NHLBI NIH HHS/United States GR - R01 AG023629/AG/NIA NIH HHS/United States GR - R01 AG027058/AG/NIA NIH HHS/United States GR - N01 HC045133/HC/NHLBI NIH HHS/United States GR - N01HC85080/HL/NHLBI NIH HHS/United States GR - N01 HC035129/HC/NHLBI NIH HHS/United States GR - R56 AG023629/AG/NIA NIH HHS/United States GR - N01HC85081/HL/NHLBI NIH HHS/United States GR - R01 DE 13094/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120427 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R SB - AIM SB - IM CIN - Lancet. 2012 Jun 2;379(9831):2028-30. PMID: 22541276 CIN - Dtsch Med Wochenschr. 2012 Sep;137(36):1732. PMID: 22933192 CIN - Nat Rev Cardiol. 2012 Jul;9(7):376. PMID: 22584942 EIN - Lancet. 2012 Aug 4;380(9840):474 MH - Cardiovascular Diseases/*diagnostic imaging/epidemiology/pathology MH - *Carotid Intima-Media Thickness MH - Disease Progression MH - Follow-Up Studies MH - Humans MH - Myocardial Infarction/diagnostic imaging/epidemiology/pathology MH - Prognosis MH - Risk Assessment/methods MH - Stroke/diagnostic imaging/epidemiology/pathology PMC - PMC3918517 MID - NIHMS538530 IR - Yanez D FIR - Yanez, David IR - Juraska M FIR - Juraska, Michal IR - Srinivasan SR FIR - Srinivasan, Sathanur R IR - Berenson GS FIR - Berenson, Gerald S IR - Sacco RL FIR - Sacco, Ralph L IR - Witteman JC FIR - Witteman, Jacqueline C M IR - Breteler MM FIR - Breteler, Monique M B IR - Hofman A FIR - Hofman, Albert IR - Johnsen SH FIR - Johnsen, Stein H IR - Stensland E FIR - Stensland, Eva IR - Agewall S FIR - Agewall, Stefan IR - Sitzer M FIR - Sitzer, Matthias IR - Steinmetz H FIR - Steinmetz, Helmuth IR - Dorr M FIR - Dorr, Marcus IR - Schminke U FIR - Schminke, Ulf IR - Poppert H FIR - Poppert, Holger IR - Bickel H FIR - Bickel, Horst IR - Kauhanen J FIR - Kauhanen, Jussi IR - Ronkainen K FIR - Ronkainen, Kimmo IR - Empana JP FIR - Empana, Jean Philippe IR - Ducimetiere P FIR - Ducimetiere, Pierre IR - Norata GD FIR - Norata, Giuseppe D IR - Grigore L FIR - Grigore, Liliana IR - Price J FIR - Price, Jackie IR - Fowkes G FIR - Fowkes, Gerry IR - Willeit J FIR - Willeit, Johann IR - Bokemark L FIR - Bokemark, Lena IR - Fagerberg B FIR - Fagerberg, Bjorn EDAT- 2012/05/01 06:00 MHDA- 2012/07/18 06:00 CRDT- 2012/05/01 06:00 PHST- 2012/05/01 06:00 [entrez] PHST- 2012/05/01 06:00 [pubmed] PHST- 2012/07/18 06:00 [medline] AID - S0140-6736(12)60441-3 [pii] AID - 10.1016/S0140-6736(12)60441-3 [doi] PST - ppublish SO - Lancet. 2012 Jun 2;379(9831):2053-62. doi: 10.1016/S0140-6736(12)60441-3. Epub 2012 Apr 27. PMID- 22386878 OWN - NLM STAT- MEDLINE DCOM- 20120927 LR - 20161126 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1822 IP - 6 DP - 2012 Jun TI - Effect of Tie-2 conditional deletion of BDNF on atherosclerosis in the ApoE null mutant mouse. PG - 927-35 LID - 10.1016/j.bbadis.2012.02.014 [doi] AB - The reduced expression (haplodeficiency) of the main brain derived neurotrophic factor receptor, namely TrkB is associated with reduced atherosclerosis, smooth muscle cells accumulation and collagen content in the lesion. These data support the concept that brain derived neurotrophic factor of vascular origin may contribute to atherosclerosis. However, to date, no experimental approach was possible to investigate this issue due to the lethality of brain derived neurotrophic factor null mice. To overcome these limitations, we generated a mouse model with a conditional deletion of brain derived neurotrophic factor in endothelial cells (Tie-2 Cre recombinase) on an atherosclerotic prone background (apolipoprotein E knock out) and investigated the effect of conditional brain derived neurotrophic factor deficiency on atherosclerosis. Despite brain derived neurotrophic factor reduction in the vascular wall, mice with conditional deletion of brain derived neurotrophic factor did not develop larger atherosclerotic lesion compared to controls. Smooth muscle cell content as well as the distribution of total and fibrillar collagen was similar in the atherosclerotic lesions from mice with brain derived neurotrophic factor conditional deficiency compared to controls. Finally an extended gene expression analysis failed to identify pro-atherogenic gene expression patterns among the animal with brain derived neurotrophic factor deficiency. In spite of the reduced brain derived neurotrophic factor expression, similar atherosclerosis development was observed in the brain derived neurotrophic factor conditional deficient mouse compared to controls. These pieces of evidence indicate that endothelial derived-brain derived neurotrophic factor is not a pro-atherogenic factor and would rather suggest to investigate the role of other TrkB activators on atherosclerosis. CI - (c) 2012 Elsevier B.V. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Italy. Sanilo.Norata@unimi.it FAU - Pulakazhi Venu, Vivek Krishna AU - Pulakazhi Venu VK FAU - Callegari, Elisa AU - Callegari E FAU - Paloschi, Valentina AU - Paloschi V FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120222 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Apolipoproteins E) RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, TIE-2) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Tek protein, mouse) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM MH - Animals MH - Apolipoproteins E/deficiency/genetics/*metabolism MH - Atherosclerosis/genetics/*metabolism/*pathology MH - Brain-Derived Neurotrophic Factor/deficiency/genetics/*metabolism MH - Disease Models, Animal MH - Endothelial Cells/metabolism/pathology MH - Integrases/genetics MH - Macrophages/metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Receptor Protein-Tyrosine Kinases/genetics MH - Receptor, TIE-2 MH - Receptor, trkB/metabolism MH - Sequence Deletion EDAT- 2012/03/06 06:00 MHDA- 2012/09/28 06:00 CRDT- 2012/03/06 06:00 PHST- 2011/11/03 00:00 [received] PHST- 2012/01/26 00:00 [revised] PHST- 2012/02/14 00:00 [accepted] PHST- 2012/03/06 06:00 [entrez] PHST- 2012/03/06 06:00 [pubmed] PHST- 2012/09/28 06:00 [medline] AID - S0925-4439(12)00042-7 [pii] AID - 10.1016/j.bbadis.2012.02.014 [doi] PST - ppublish SO - Biochim Biophys Acta. 2012 Jun;1822(6):927-35. doi: 10.1016/j.bbadis.2012.02.014. Epub 2012 Feb 22. PMID- 22573072 OWN - NLM STAT- MEDLINE DCOM- 20120831 LR - 20171116 IS - 1473-5598 (Electronic) IS - 0263-6352 (Linking) VI - 30 IP - 6 DP - 2012 Jun TI - Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: a role for organ damage markers. PG - 1056-64 LID - 10.1097/HJH.0b013e3283525715 [doi] AB - BACKGROUND: Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process. OBJECTIVE: Our aim was to evaluate the influence of implementation of SCORE charts with widely available indexes of organ damage, with the purpose to ameliorate individual risk assessment. METHODOLOGY: We searched www.Pubmed.gov for evidence about the predictive value of left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU) and metabolic syndrome on different risk profiles estimated by SCORE. Interventional and observational trials including at least 200 patients and published after 2000 were selected. RESULTS: The presence of organ damage as well as the number of abnormal parameters indicating organ damage is associated with increased cardiovascular risk, independently of SCORE. In the area of high risk, the impact of different markers of organ damage is heterogeneous. Combined risk models of SCORE and subclinical organ damage have major impact on risk stratification and may impact on recommendation in primary prevention in all SCORE categories. CONCLUSION: Available evidence suggests a tangible clinical advantage of adding the evaluation of simple organ damage markers to risk charts in cardiovascular risk prediction. FAU - Volpe, Massimo AU - Volpe M AD - Cardiology Department of Clinical and Molecular Medicine, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy. massimo.volpe@uniroma1.it FAU - Battistoni, Allegra AU - Battistoni A FAU - Tocci, Giuliano AU - Tocci G FAU - Rosei, Enrico Agabiti AU - Rosei EA FAU - Catapano, Alberico L AU - Catapano AL FAU - Coppo, Rosanna AU - Coppo R FAU - del Prato, Stefano AU - del Prato S FAU - Gentile, Sandro AU - Gentile S FAU - Mannarino, Elmo AU - Mannarino E FAU - Novo, Salvatore AU - Novo S FAU - Prisco, Domenico AU - Prisco D FAU - Mancia, Giuseppe AU - Mancia G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - J Hypertens JT - Journal of hypertension JID - 8306882 RN - 0 (Biomarkers) SB - IM MH - Albuminuria/pathology MH - Biomarkers/*metabolism MH - Coronary Disease/*pathology/physiopathology MH - Glomerular Filtration Rate MH - Humans MH - Metabolic Syndrome/pathology MH - Risk Assessment EDAT- 2012/05/11 06:00 MHDA- 2012/09/01 06:00 CRDT- 2012/05/11 06:00 PHST- 2012/05/11 06:00 [entrez] PHST- 2012/05/11 06:00 [pubmed] PHST- 2012/09/01 06:00 [medline] AID - 10.1097/HJH.0b013e3283525715 [doi] AID - 00004872-201206000-00002 [pii] PST - ppublish SO - J Hypertens. 2012 Jun;30(6):1056-64. doi: 10.1097/HJH.0b013e3283525715. PMID- 22697078 OWN - NLM STAT- MEDLINE DCOM- 20120724 LR - 20170214 IS - 0394-6320 (Print) IS - 0394-6320 (Linking) VI - 25 IP - 2 DP - 2012 Apr-Jun TI - MicroRNA 143-145 deficiency impairs vascular function. PG - 467-74 AB - MicroRNAs are required for vascular smooth muscle growth, differentiation and function. MiR143-145 modulates cytoskeletal dynamics and acquisition of the contractile phenotype by smooth muscle cells. Lack of this miRNA cluster results in decreased blood pressure and reduced vasocontraction. As all these observations point to a key role for miR143-145 in the vasculature, we investigated whether miR143-145 deficiency is associated with impaired vascular tone. Vasocontraction was assessed in isolated aortic rings from miR143-145 KO and wild type animals incubated with increasing concentrations of phenylephrine (10(-9)M to 10(-5)M) or KCl 0.3M. In both cases, aortic vessel contraction was dramatically reduced in miR143-145 KO animals compared to controls. Next, aortic rings were pre-contracted with phenylephrine (EC60: 10(-7)M) and concentration responses for acetylcholine were obtained. A significantly reduced vasodilation was observed in miR143-145 KO animals compared to controls and similar results were obtained when an exogenous donor of nitric oxide (sodium nitroprusside) was used. Endothelial nitric oxide synthase or guanylate cyclase mRNA expression were not different between the animal groups thus suggesting to investigate the effect of other vasodilators. Isoprenaline mediated vasodilation was significantly reduced in miR143-145 KO animals compared to controls in the absence or in the presence of the guanylate cyclase inhibitor ODQ (10(-4)M), suggesting that also beta adrenergic vasodilation is impaired following miR143-145 deficiency. Finally, the effect of a stable mimetic prostacyclin, namely iloprost, was investigated and again a reduced vasodilation was observed in miR143-145 KO animals. MiR143-145 deficiency is associated not only with altered vasocontraction but also with impaired vasodilation, which probably reflects the impaired VSMC differentiation phenotype reported in miR143-145 KO animals. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Milan, Italy. danilo.norata@unimi.it FAU - Pinna, C AU - Pinna C FAU - Zappella, F AU - Zappella F FAU - Elia, L AU - Elia L FAU - Sala, A AU - Sala A FAU - Condorelli, G AU - Condorelli G FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Int J Immunopathol Pharmacol JT - International journal of immunopathology and pharmacology JID - 8911335 RN - 0 (MIRN145 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn143 microRNA, mouse) RN - 0 (Vasoconstrictor Agents) RN - 0 (Vasodilator Agents) SB - IM MH - Animals MH - Aorta, Thoracic/metabolism MH - Cell Differentiation MH - Dose-Response Relationship, Drug MH - Down-Regulation MH - Genotype MH - Male MH - Mice MH - Mice, Knockout MH - MicroRNAs/genetics/*metabolism MH - Muscle, Smooth, Vascular/drug effects/*metabolism MH - Myocytes, Smooth Muscle/drug effects/*metabolism MH - Phenotype MH - *Vasoconstriction/drug effects MH - Vasoconstrictor Agents/pharmacology MH - *Vasodilation/drug effects MH - Vasodilator Agents/pharmacology EDAT- 2012/06/16 06:00 MHDA- 2012/07/25 06:00 CRDT- 2012/06/16 06:00 PHST- 2012/06/16 06:00 [entrez] PHST- 2012/06/16 06:00 [pubmed] PHST- 2012/07/25 06:00 [medline] AID - 16 [pii] AID - 10.1177/039463201202500216 [doi] PST - ppublish SO - Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):467-74. doi: 10.1177/039463201202500216. PMID- 20884190 OWN - NLM STAT- MEDLINE DCOM- 20120723 LR - 20120319 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 22 IP - 4 DP - 2012 Apr TI - How many patients need statin treatment in a low-cardiovascular-risk country? Low-density lipoprotein-cholesterol target and distance from target distribution in an Italian cohort. PG - 327-36 LID - 10.1016/j.numecd.2010.06.009 [doi] AB - BACKGROUND AND AIM: To assess cardiovascular risk distribution, distribution of individual low-density lipoprotein (LDL)-cholesterol target and distance of LDL cholesterol from the target in a representative sample of the Italian population. METHODS AND RESULTS: Cross-sectional, population-based study of a representative sample of the Italian adult population, comprising 5458 individuals (from 40 to 79 years of age, both sexes) from general practices in Italy. Of the subjects, 65.2% were in the low-cardiovascular-risk class, whereas 10.5%, 18.3% and 6.0% had moderate, high, and very high cardiovascular risk profiles, respectively; 8.2% of the subjects were treated with statins at enrolment. Of the cohort, 68.3% displayed LDL-cholesterol values below their LDL target, as calculated according to their individual risk profile. Among the 31.7% 'not at target', 42.3% were 40% over their LDL target. CONCLUSIONS: About two-thirds of adults in a low-cardiovascular-risk country, such as Italy, have LDL-cholesterol levels 'at target', as defined in current guidelines. Accordingly, the remaining subjects require a lifestyle or pharmacological intervention to reach their target; 24% of the total cohort, in detail, need to be treated with a statin (or to continue the prescribed statin treatment) to reach the proper LDL target. This type of data analysis might help to optimise resource allocation in preventive medicine. CI - Copyright (c) 2010 Elsevier B.V. All rights reserved. FAU - Poli, A AU - Poli A AD - Epidemiology and Preventive Pharmacology Centre, SEFAP, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. poli@nutrition-foundation.it FAU - Tragni, E AU - Tragni E FAU - Casula, M AU - Casula M FAU - Filippi, A AU - Filippi A FAU - Diotti, R AU - Diotti R FAU - Brignoli, O AU - Brignoli O FAU - Cricelli, C AU - Cricelli C FAU - Catapano, A L AU - Catapano AL CN - CHECK Group LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100929 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Aged MH - Cardiovascular Diseases/blood/*etiology MH - Cholesterol, LDL/*blood MH - Cohort Studies MH - Cross-Sectional Studies MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Italy MH - Male MH - Middle Aged IR - Anna AM FIR - Anna, Aalders Maria IR - Giuseppe A FIR - Giuseppe, Abbate IR - Riccardo A FIR - Riccardo, Agati IR - Raffaele A FIR - Raffaele, Alano IR - Mauro A FIR - Mauro, Alba IR - Silvia A FIR - Silvia, Alemagna IR - Massimo A FIR - Massimo, Alunni IR - Fabio A FIR - Fabio, Amato IR - Erminia A FIR - Erminia, Ammendola IR - Vincenzo A FIR - Vincenzo, Amodeo IR - Giovanni A FIR - Giovanni, Amoretti IR - Alberto A FIR - Alberto, Andrani IR - Ivo A FIR - Ivo, Antiga IR - Appolonia G FIR - Appolonia, Giorgio IR - Enrico A FIR - Enrico, Aramini IR - Emilio AM FIR - Emilio, Arisi Marco IR - Adriano A FIR - Adriano, Artebani IR - Massimiliano A FIR - Massimiliano, Atzei IR - Micheline A FIR - Micheline, Azzolini IR - Franco B FIR - Franco, Bagagli IR - Lorella B FIR - Lorella, Baldicchi IR - Banzi R FIR - Banzi, Roberta IR - Maria BE FIR - Maria, Barba Ettore IR - Claudio BP FIR - Claudio, Barbato Pasquale IR - Gino B FIR - Gino, Barral IR - Alessandro B FIR - Alessandro, Battaggia IR - Doriano B FIR - Doriano, Battigelli IR - Marina B FIR - Marina, Baudi IR - Giovanni B FIR - Giovanni, Bellumori IR - Giuseppe B FIR - Giuseppe, Beltrami IR - Maria BA FIR - Maria, Benincasa Anna IR - Mario B FIR - Mario, Berardi IR - Claudio B FIR - Claudio, Berlengiero IR - Stefano B FIR - Stefano, Bernardelli IR - Giuseppe B FIR - Giuseppe, Bernardi IR - Evandro B FIR - Evandro, Bertelle IR - Gianluca B FIR - Gianluca, Bettini IR - Giuseppe B FIR - Giuseppe, Bevacqua IR - Stefano B FIR - Stefano, Bevilacqua IR - Giuseppe B FIR - Giuseppe, Bianconi IR - Giovanni B FIR - Giovanni, Biggioggero IR - Vincenzo B FIR - Vincenzo, Bini IR - Giancarlo B FIR - Giancarlo, Bocchino IR - Nicolfranco B FIR - Nicolfranco, Boccone IR - Giancarlo B FIR - Giancarlo, Boito IR - Maria BA FIR - Maria, Bollo Alberto IR - Salvatore B FIR - Salvatore, Boncompagni IR - Bond G FIR - Bond, Giuseppe IR - Grazia BM FIR - Grazia, Bonesi Maria IR - Gianfranco B FIR - Gianfranco, Bono IR - Federica B FIR - Federica, Boscaro IR - Paolo B FIR - Paolo, Bossi IR - Giulio B FIR - Giulio, Bozza IR - Bracone E FIR - Bracone, Enrico IR - Lucio B FIR - Lucio, Brandodoro IR - Pierclaudio B FIR - Pierclaudio, Brasesco IR - Adele B FIR - Adele, Breviario IR - Antonio B FIR - Antonio, Brizzi IR - Maurizio B FIR - Maurizio, Brugnetta IR - Giuseppe B FIR - Giuseppe, Bruno IR - Giuseppe B FIR - Giuseppe, Buemi IR - Carmine B FIR - Carmine, Bufano IR - Tiziano B FIR - Tiziano, Bugli IR - Burigo D FIR - Burigo, Daniela IR - Agostino B FIR - Agostino, Buzzatti IR - Antonio CO FIR - Antonio, Caccamo Orazio IR - Danilo C FIR - Danilo, Cadamosti IR - Francesco C FIR - Francesco, Cagliesi IR - Caleffa M FIR - Caleffa, Manuela IR - Nicolo' C FIR - Nicolo', Cammisa IR - Franceso C FIR - Franceso, Campo IR - Margherita C FIR - Margherita, Campobello IR - Stanislao C FIR - Stanislao, Caputo IR - Caraccio N FIR - Caraccio, Nicola IR - Silvio C FIR - Silvio, Cardi IR - Fulvio C FIR - Fulvio, Cardinale EDAT- 2010/10/05 06:00 MHDA- 2012/07/24 06:00 CRDT- 2010/10/02 06:00 PHST- 2009/12/03 00:00 [received] PHST- 2010/03/29 00:00 [revised] PHST- 2010/06/28 00:00 [accepted] PHST- 2010/10/02 06:00 [entrez] PHST- 2010/10/05 06:00 [pubmed] PHST- 2012/07/24 06:00 [medline] AID - S0939-4753(10)00163-8 [pii] AID - 10.1016/j.numecd.2010.06.009 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2012 Apr;22(4):327-36. doi: 10.1016/j.numecd.2010.06.009. Epub 2010 Sep 29. PMID- 22022768 OWN - NLM STAT- MEDLINE DCOM- 20120613 LR - 20121115 IS - 1875-6212 (Electronic) IS - 1570-1611 (Linking) VI - 10 IP - 2 DP - 2012 Mar TI - Statin-induced myotoxicity: pharmacokinetic differences among statins and the risk of rhabdomyolysis, with particular reference to pitavastatin. PG - 257-67 AB - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely prescribed therapeutic class of drugs worldwide, with established clinical benefits both in terms of improving serum lipid profiles and reducing cardiovascular events and mortality. Although statins have a favorable risk-to-benefit ratio, they have the potential to cause adverse events which can result in muscular inflammation (myositis), muscle breakdown (rhabdomyolysis) and, ultimately, kidney failure. While the incidence of rhabdomyolysis is approximately 3.4 cases per 100,000 person-years with standard-dose statin therapy, the risk of developing the condition increases substantially at higher therapeutic doses. This effect may be exacerbated by prescribing statins in combination with certain other medications because drug drug interactions increase statin exposure by interacting with enzymes that would normally be involved in their metabolism and clearance. Co-administration of drugs that inhibit the cytochrome P450 (CYP) enzymes responsible for metabolizing statins, or that interact with the organic anion-transporting polypeptides (OATPs) responsible for statin uptake into hepatocytes, substantially increases the risk of developing myotoxicity. Such effects vary among statins according to their metabolic profile. For example, pitavastatin, a novel statin approved for the treatment of hypercholesterolemia and combined (mixed) dyslipidemia, is not catabolized by CYP3A4, unlike other lipophilic statins, and may be less dependent on the OATP1B1 transporter for its uptake into hepatocytes before clearance. Such differences in drug drug interaction profiles among available statins offer the possibility of reducing the risk of myotoxicity among high-risk patients. FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. alberico.catapano@unimi.it LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United Arab Emirates TA - Curr Vasc Pharmacol JT - Current vascular pharmacology JID - 101157208 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipids) RN - 0 (Quinolines) RN - M5681Q5F9P (pitavastatin) SB - IM MH - Cardiovascular Diseases/prevention & control MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Dyslipidemias/complications/drug therapy MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/pharmacokinetics/therapeutic use MH - Hypercholesterolemia/complications/drug therapy MH - Lipids/blood MH - Quinolines/*adverse effects/pharmacokinetics/therapeutic use MH - Rhabdomyolysis/*chemically induced/epidemiology MH - Risk EDAT- 2011/10/26 06:00 MHDA- 2012/06/14 06:00 CRDT- 2011/10/26 06:00 PHST- 2011/06/23 00:00 [received] PHST- 2011/07/15 00:00 [revised] PHST- 2011/09/20 00:00 [accepted] PHST- 2011/10/26 06:00 [entrez] PHST- 2011/10/26 06:00 [pubmed] PHST- 2012/06/14 06:00 [medline] AID - BSP/CVP/E-Pub/0000175 [pii] PST - ppublish SO - Curr Vasc Pharmacol. 2012 Mar;10(2):257-67. PMID- 22176652 OWN - NLM STAT- MEDLINE DCOM- 20120521 LR - 20161125 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 220 IP - 2 DP - 2012 Feb TI - Proprotein convertase subtilisin kexin type 9 (PCSK9) secreted by cultured smooth muscle cells reduces macrophages LDLR levels. PG - 381-6 LID - 10.1016/j.atherosclerosis.2011.11.026 [doi] AB - OBJECTIVE: Proprotein convertase subtilisin kexin type 9 (PCSK9) is an important regulator of hepatic low-density lipoprotein (LDL)-cholesterol levels. Although PCSK9 is mainly of hepatic origin, extra-hepatic tissues significantly contribute to PCSK9 production and, potentially, local regulation of LDL receptor expression. METHODS AND RESULTS: In the present study we show that, among vascular cells, PCSK9 is expressed in smooth muscle cells (SMCs) but not in endothelial cells, macrophages and monocytes. PCSK9 was also detectable in human atherosclerotic plaques. Conditioned media from SMCs significantly reduced LDLR expression in human macrophage and in the macrophage cell line J774. Co-culture experiments also demonstrated the influence of SMCs on LDLR expression in J774. PCSK9 released from SMCs directly regulated LDLR expression in macrophages as demonstrated by retroviral overexpression or knockdown of PCSK9 with small interfering RNA and by using recombinant PCSK9. Moreover, the proteolytic activity of PCSK9 was not required for LDLR downregulation since cultured media containing either the catalytic inactive PCSK9 or PCSK9 WT had a similar effect on LDLR in J774. Finally, conditioned media from SMCs affected beta-VLDL cholesterol uptake and PCSK9 expression reduced both LDLR and LDL uptake in J774. CONCLUSIONS: Taken together our data indicate that PCSK9 secreted by human SMCs is functionally active and capable of reducing LDLR expression in macrophages. A possible direct role for this protein in foam cell formation and atherogenesis is suggested. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Ferri, Nicola AU - Ferri N AD - Department of Pharmacological Sciences, University of Milan, 20133, Milan, Italy. nicola.ferri@unimi.it FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Pirillo, Angela AU - Pirillo A FAU - Cipollone, Francesco AU - Cipollone F FAU - Mezzetti, Andrea AU - Mezzetti A FAU - Pacia, Stefano AU - Pacia S FAU - Corsini, Alberto AU - Corsini A FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111125 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Cholesterol, VLDL) RN - 0 (Culture Media, Conditioned) RN - 0 (Lipoproteins, IDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Animals MH - Biological Transport MH - Cell Line MH - Cholesterol, VLDL/metabolism MH - Culture Media, Conditioned/metabolism MH - Down-Regulation MH - Humans MH - Lipoproteins, IDL/metabolism MH - Lipoproteins, LDL/metabolism MH - Macrophages/*enzymology MH - Mice MH - Muscle, Smooth, Vascular/*enzymology MH - Myocytes, Smooth Muscle/*enzymology MH - *Paracrine Communication MH - Proprotein Convertase 9 MH - Proprotein Convertases/genetics/*metabolism MH - RNA Interference MH - Receptors, LDL/*metabolism MH - Serine Endopeptidases/genetics/*metabolism MH - Time Factors MH - Transfection EDAT- 2011/12/20 06:00 MHDA- 2012/05/23 06:00 CRDT- 2011/12/20 06:00 PHST- 2011/06/15 00:00 [received] PHST- 2011/11/17 00:00 [revised] PHST- 2011/11/17 00:00 [accepted] PHST- 2011/12/20 06:00 [entrez] PHST- 2011/12/20 06:00 [pubmed] PHST- 2012/05/23 06:00 [medline] AID - S0021-9150(11)01097-5 [pii] AID - 10.1016/j.atherosclerosis.2011.11.026 [doi] PST - ppublish SO - Atherosclerosis. 2012 Feb;220(2):381-6. doi: 10.1016/j.atherosclerosis.2011.11.026. Epub 2011 Nov 25. PMID- 23130116 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121107 LR - 20181113 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 1 IP - 1 DP - 2012 Feb TI - Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models. PG - 27-41 LID - 10.1161/JAHA.111.000125 [doi] AB - BACKGROUND#ENTITYSTARTX02014;: Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naive CD4(+)T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4(+)T-cell subsets and atherosclerosis. METHODS AND RESULTS#ENTITYSTARTX02014;: We analyzed 57 subsets of circulating CD4(+)T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (T(EM): CD3(+)CD4(+)CD45RA(-)CD45RO(+)CCR7(-) cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P<0.001). Of note, a significant correlation between T(EM) and low-density lipoproteins was observed. In the second cohort (n=130), T(EM) levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA-DR(+)T(EM) were the T(EM) subpopulation with the strongest association with the atherosclerotic process (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, T(EM) (identified as CD4(+)CD44(+)CD62L(-)) were significantly increased in low-density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56; P<0.01). CONCLUSIONS#ENTITYSTARTX02014;: Circulating T(EM) cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4(+)T-cell subset related to the atherosclerotic process. (J Am Heart Assoc. 2012;1:27-41.). FAU - Ammirati, Enrico AU - Ammirati E AD - Clinical Cardiovascular Biology Centre, San Raffaele Scientific Institute and the Universita Vita-Salute San Raffaele , Milan, Italy (E.A., D.C., M.B.) ; Heart Transplantation Division, Ospedale Niguarda Ca' Granda , Milan, Italy (E.A.) ; Heart Care Foundation , Florence, Italy (E.A., A.M.). FAU - Cianflone, Domenico AU - Cianflone D FAU - Vecchio, Viviana AU - Vecchio V FAU - Banfi, Michela AU - Banfi M FAU - Vermi, Anna C AU - Vermi AC FAU - De Metrio, Monica AU - De Metrio M FAU - Grigore, Liliana AU - Grigore L FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Pirillo, Angela AU - Pirillo A FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Manfredi, Angelo A AU - Manfredi AA FAU - Catapano, Alberico L AU - Catapano AL FAU - Maseri, Attilio AU - Maseri A FAU - Palini, Alessio G AU - Palini AG FAU - Norata, Giuseppe D AU - Norata GD LA - eng PT - Journal Article DEP - 20120220 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 PMC - PMC3487313 OTO - NOTNLM OT - C-c chemokine receptor type 7 OT - atherosclerosis OT - chemokines OT - coronary artery disease OT - effector memory T cells EDAT- 2012/11/07 06:00 MHDA- 2012/11/07 06:01 CRDT- 2012/11/07 06:00 PHST- 2011/12/07 00:00 [received] PHST- 2011/12/21 00:00 [accepted] PHST- 2012/11/07 06:00 [entrez] PHST- 2012/11/07 06:00 [pubmed] PHST- 2012/11/07 06:01 [medline] AID - 10.1161/JAHA.111.000125 [doi] AID - jah34 [pii] PST - ppublish SO - J Am Heart Assoc. 2012 Feb;1(1):27-41. doi: 10.1161/JAHA.111.000125. Epub 2012 Feb 20. PMID- 21783193 OWN - NLM STAT- MEDLINE DCOM- 20120420 LR - 20111226 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 220 IP - 1 DP - 2012 Jan TI - Emerging role of high density lipoproteins as a player in the immune system. PG - 11-21 LID - 10.1016/j.atherosclerosis.2011.06.045 [doi] AB - High density lipoproteins (HDL) possess a number of physiological activities. The most studied and, perhaps, better understood is the ability of HDL to promote excess cholesterol efflux from peripheral tissues and transport to the liver for excretion, a mechanism believed to confer protection against atherosclerotic cardiovascular disease. The ability of HDL to modulate cholesterol bioavailability in the lipid rafts, membrane microdomains enriched in glycosphingolipids and cholesterol, is evolutionary conserved and affects the properties of cells involved in the innate and adaptive immune response, tuning inflammatory response and antigen presentation functions in macrophages as well as B and T cell activation. Also sphingosine-1 phosphate (S1P), a major active sphingolipid carried by HDL, is of relevance in the pathogenesis of several immuno-inflammatory disorders through the modulation of macrophage and lymphocyte functions. Furthermore, HDL influence the humoral innate immunity by modulating the activation of the complement system and the expression of pentraxin 3 (PTX3). Finally, in humans, HDL levels and functions are altered in several immune-mediated disorders, such as rheumatoid arthritis, systemic lupus eritematosus, Crohn's disease and multiple sclerosis as well as during inflammatory responses. Altogether these observations suggest that the effects of HDL in immunity could be related, to either the ability of HDL to modulate cholesterol content in immune cell lipid rafts and to their role as reservoir for several biologically active substances that may impact the immune system. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Italy. Danilo.Norata@unimi.it FAU - Pirillo, Angela AU - Pirillo A FAU - Ammirati, Enrico AU - Ammirati E FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20110702 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins, HDL) SB - IM MH - *Adaptive Immunity MH - Animals MH - Humans MH - Immune System/*immunology MH - Immune System Diseases/immunology MH - *Immunity, Innate MH - Lipoproteins, HDL/*immunology MH - Signal Transduction EDAT- 2011/07/26 06:00 MHDA- 2012/04/21 06:00 CRDT- 2011/07/26 06:00 PHST- 2011/04/11 00:00 [received] PHST- 2011/06/08 00:00 [revised] PHST- 2011/06/24 00:00 [accepted] PHST- 2011/07/26 06:00 [entrez] PHST- 2011/07/26 06:00 [pubmed] PHST- 2012/04/21 06:00 [medline] AID - S0021-9150(11)00567-3 [pii] AID - 10.1016/j.atherosclerosis.2011.06.045 [doi] PST - ppublish SO - Atherosclerosis. 2012 Jan;220(1):11-21. doi: 10.1016/j.atherosclerosis.2011.06.045. Epub 2011 Jul 2. PMID- 23152673 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121119 LR - 20181113 IS - 1177-889X (Electronic) IS - 1177-889X (Linking) VI - 6 DP - 2012 TI - Adherence to lipid-lowering treatment: the patient perspective. PG - 805-14 LID - 10.2147/PPA.S29092 [doi] AB - Despite the widespread prescription of highly effective lipid-lowering medications, such as the HMG-CoA reductase inhibitors (statins), a large portion of the population has lipid levels higher than the recommended goals. Treatment failures have been attributed to a variety of causes but the most important is likely to be poor adherence to therapy in the form of irregular or interrupted intake and the high frequency of discontinuation or lack of persistence. Adherence is a multidimensional phenomenon determined by the interplay of patient factors, physician factors, and health care system factors. Patients' knowledge and beliefs about their illness, motivation to manage it, confidence in their ability to engage in illness-management behaviors, and expectations regarding the outcome of treatment and the consequences of poor adherence interact to influence adherence behavior. Patient-related factors account for the largest incremental explanatory power in predicting adherence. This article provides an overview of this critical issue, focusing on patient role in determining adherence level to lipid-lowering therapy. FAU - Casula, Manuela AU - Casula M AD - Epidemiology and Preventive Pharmacology Centre (SEFAP), Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Tragni, Elena AU - Tragni E FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article DEP - 20121108 PL - New Zealand TA - Patient Prefer Adherence JT - Patient preference and adherence JID - 101475748 PMC - PMC3496534 OTO - NOTNLM OT - health behavior OT - hyperlipidemia/drug therapy OT - medication adherence OT - patient preference EDAT- 2012/11/16 06:00 MHDA- 2012/11/16 06:01 CRDT- 2012/11/16 06:00 PHST- 2012/11/16 06:00 [entrez] PHST- 2012/11/16 06:00 [pubmed] PHST- 2012/11/16 06:01 [medline] AID - 10.2147/PPA.S29092 [doi] AID - ppa-6-805 [pii] PST - ppublish SO - Patient Prefer Adherence. 2012;6:805-14. doi: 10.2147/PPA.S29092. Epub 2012 Nov 8. PMID- 22347434 OWN - NLM STAT- MEDLINE DCOM- 20120731 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 2 DP - 2012 TI - Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population. PG - e31086 LID - 10.1371/journal.pone.0031086 [doi] AB - BACKGROUND AND PURPOSE: The lectin-like oxidised LDL receptor-1 (OLR1) gene encodes a scavenger receptor implicated in the pathogenesis of atherosclerosis. Although functional roles have been suggested for two variants, epidemiological studies on OLR1 have been inconsistent. METHODS: We tested the association between the non-synonymous substitution K167N (rs11053646) and intima media thickness of the common carotid artery (CCA-IMT) in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study). RESULTS: Significantly increased IMT was observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotype. Functional analysis on macrophages suggested a decreased association to Ox-LDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers. CONCLUSIONS: These data suggest that the 167N variant of LOX-1 receptor affects the atherogenic process in the carotid artery prior to evidence of disease through an inflammatory process. FAU - Predazzi, Irene Marta AU - Predazzi IM AD - Department of Biopathology and Diagnostic Imaging, Section of Medical Genetics, School of Medicine, Tor Vergata University, Rome, Italy. irene.m.predazzi@Vanderbilt.Edu FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Vecchione, Lucia AU - Vecchione L FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Amati, Francesca AU - Amati F FAU - Grigore, Liliana AU - Grigore L FAU - Cutuli, Lucia AU - Cutuli L FAU - Pirillo, Angela AU - Pirillo A FAU - Tramontana, Simona AU - Tramontana S FAU - Romeo, Francesco AU - Romeo F FAU - Novelli, Giuseppe AU - Novelli G FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng GR - T32 HL007751/HL/NHLBI NIH HHS/United States GR - 2T32HL007751-16A2/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120209 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (OLR1 protein, human) RN - 0 (Scavenger Receptors, Class E) SB - IM MH - Amino Acid Substitution MH - Carotid Artery Diseases/epidemiology/*genetics/*pathology MH - Carotid Artery, Common/*pathology MH - Female MH - Genotype MH - Humans MH - Inflammation MH - Macrophages MH - Male MH - *Polymorphism, Single Nucleotide MH - Scavenger Receptors, Class E/*genetics MH - Sex Factors MH - Tunica Intima/pathology MH - Tunica Media/pathology PMC - PMC3276570 EDAT- 2012/02/22 06:00 MHDA- 2012/08/01 06:00 CRDT- 2012/02/21 06:00 PHST- 2011/06/15 00:00 [received] PHST- 2012/01/02 00:00 [accepted] PHST- 2012/02/21 06:00 [entrez] PHST- 2012/02/22 06:00 [pubmed] PHST- 2012/08/01 06:00 [medline] AID - 10.1371/journal.pone.0031086 [doi] AID - PONE-D-11-10752 [pii] PST - ppublish SO - PLoS One. 2012;7(2):e31086. doi: 10.1371/journal.pone.0031086. Epub 2012 Feb 9. PMID- 22115524 OWN - NLM STAT- MEDLINE DCOM- 20120320 LR - 20140430 IS - 1579-2242 (Electronic) IS - 0300-8932 (Linking) VI - 64 IP - 12 DP - 2011 Dec TI - [ESC/EAS Guidelines for the management of dyslipidaemias]. PG - 1168.e1-1168.e60 LID - 10.1016/j.recesp.2011.09.014 [doi] FAU - Reiner, Zeljko AU - Reiner Z AD - University Hospital Center Zagreb, School of Medicine, University of Zagreb, Salata 2, 10 000 Zagreb, Croacia. zreiner@kbc-zagreb.hr FAU - Catapano, Alberico L AU - Catapano AL FAU - De Backer, Guy AU - De Backer G FAU - Graham, Ian AU - Graham I FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Wiklund, Olov AU - Wiklund O FAU - Agewall, Stefan AU - Agewall S FAU - Alegria, Eduardo AU - Alegria E FAU - Chapman, M John AU - Chapman MJ FAU - Durrington, Paul AU - Durrington P FAU - Erdine, Serap AU - Erdine S FAU - Halcox, Julian AU - Halcox J FAU - Hobbs, Richard Hobbs AU - Hobbs RH FAU - Kjekshus, John Kjekshus AU - Kjekshus JK FAU - Perrone Filardi, Pasquale AU - Perrone Filardi P FAU - Riccardi, Gabriele AU - Riccardi G FAU - Storey, Robert F AU - Storey RF FAU - David, Wood AU - David W CN - Clinical Practice Guidelines Committee of the Spanish Society of Cardiology LA - spa PT - Guideline PT - Journal Article PT - Review TT - Guia de la ESC/EAS sobre el manejo de las dislipemias. PL - Spain TA - Rev Esp Cardiol JT - Revista espanola de cardiologia JID - 0404277 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipids) SB - IM CIN - Rev Esp Cardiol. 2011 Dec;64(12):1090-5. PMID: 22107831 CIN - Atherosclerosis. 2014 Apr;233(2):508-9. PMID: 24530786 MH - Algorithms MH - Cardiovascular Diseases/prevention & control MH - Dyslipidemias/drug therapy/economics/*therapy MH - Goals MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypolipidemic Agents/therapeutic use MH - Lipids/blood MH - Risk Assessment MH - Spain EDAT- 2011/11/26 06:00 MHDA- 2012/03/21 06:00 CRDT- 2011/11/26 06:00 PHST- 2011/09/16 00:00 [received] PHST- 2011/09/16 00:00 [accepted] PHST- 2011/11/26 06:00 [entrez] PHST- 2011/11/26 06:00 [pubmed] PHST- 2012/03/21 06:00 [medline] AID - S0300-8932(11)00834-7 [pii] AID - 10.1016/j.recesp.2011.09.014 [doi] PST - ppublish SO - Rev Esp Cardiol. 2011 Dec;64(12):1168.e1-1168.e60. doi: 10.1016/j.recesp.2011.09.014. PMID- 21943799 OWN - NLM STAT- MEDLINE DCOM- 20120202 LR - 20161125 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 21 IP - 11 DP - 2011 Nov TI - Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition. PG - 835-43 LID - 10.1016/j.numecd.2011.06.002 [doi] AB - AIMS: This short review aims at summarizing the current information on Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) structure and function focusing also on the therapeutic possibilities based on the inhibition of this protein. DATA SYNTHESIS: PCSK9 has been recently discovered as the third gene involved in autosomal dominant hypercholesterolemia. PCSK9 binds and favors degradation of the low-density lipoprotein receptor (LDLR) and thereby modulates the plasma levels of LDL-cholesterol (LDL-C). Some of the natural occurring PCSK9 mutations increase the protein function (gain of function) and cause hypercholesterolemia, whereas loss of function mutations associate with hypocholesterolemia. Since the loss of a functional PCSK9 in humans is not associated with apparent deleterious effects, this protease is an attractive target for the development of lowering plasma LDL-C agents, either alone or in combination with statins. CONCLUSION: Inhibition of PCSK9 is emerging as a novel strategy for the treatment of hypercholesterolemia and data obtained from pre-clinical studies show that use of monoclonal antibodies, antisense oligonucleotides and short interfering RNA are effective in reducing LDL-C, clinical studies, accompanied by a better understanding of PCSK9 biology, are now necessary to address whether these new compounds will have a future in clinical practice. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Tibolla, G AU - Tibolla G AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Italy. FAU - Norata, G D AU - Norata GD FAU - Artali, R AU - Artali R FAU - Meneghetti, F AU - Meneghetti F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20110923 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Cholesterol, LDL) RN - 0 (Hypolipidemic Agents) RN - 0 (Receptors, LDL) RN - 0 (Serine Proteinase Inhibitors) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - EC 3.4.21.- (Proprotein Convertases) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Animals MH - Cholesterol, LDL/blood MH - Humans MH - Hypercholesterolemia/*drug therapy/genetics MH - Hypolipidemic Agents MH - Mutation MH - Proprotein Convertase 9 MH - Proprotein Convertases MH - Receptors, LDL/metabolism MH - Serine Endopeptidases/*chemistry/genetics/*physiology MH - Serine Proteinase Inhibitors/*therapeutic use MH - Structure-Activity Relationship EDAT- 2011/09/29 06:00 MHDA- 2012/02/03 06:00 CRDT- 2011/09/28 06:00 PHST- 2011/04/27 00:00 [received] PHST- 2011/06/17 00:00 [revised] PHST- 2011/06/23 00:00 [accepted] PHST- 2011/09/28 06:00 [entrez] PHST- 2011/09/29 06:00 [pubmed] PHST- 2012/02/03 06:00 [medline] AID - S0939-4753(11)00161-X [pii] AID - 10.1016/j.numecd.2011.06.002 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2011 Nov;21(11):835-43. doi: 10.1016/j.numecd.2011.06.002. Epub 2011 Sep 23. PMID- 21881500 OWN - NLM STAT- MEDLINE DCOM- 20120109 LR - 20131121 IS - 1473-6535 (Electronic) IS - 0957-9672 (Linking) VI - 22 IP - 5 DP - 2011 Oct TI - HDLs, immunity, and atherosclerosis. PG - 410-6 LID - 10.1097/MOL.0b013e32834adac3 [doi] AB - PURPOSE OF REVIEW: HDLs possess several physiological activities that may explain their antiatherosclerotic properties. Among them, the most relevant is the ability of HDL to promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. RECENT FINDINGS: The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes. HDL also acts as a reservoir for a number of biologically active substances that may impact the immune system, and as the HDL composition varies to a large extent during inflammation. SUMMARY: The understanding of how these interactions take place and how biologically active substances can be delivered to relevant targets during atherogenesis is of great interest and may provide a better understanding for the role of HDL in atherogenesis. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Centro SISA per lo Studio dell'Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - England TA - Curr Opin Lipidol JT - Current opinion in lipidology JID - 9010000 RN - 0 (Lipoproteins, HDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Atherosclerosis/*immunology/*metabolism MH - Cholesterol/metabolism MH - Humans MH - Inflammation/immunology MH - Lipoproteins, HDL/*metabolism EDAT- 2011/09/02 06:00 MHDA- 2012/01/10 06:00 CRDT- 2011/09/02 06:00 PHST- 2011/09/02 06:00 [entrez] PHST- 2011/09/02 06:00 [pubmed] PHST- 2012/01/10 06:00 [medline] AID - 10.1097/MOL.0b013e32834adac3 [doi] PST - ppublish SO - Curr Opin Lipidol. 2011 Oct;22(5):410-6. doi: 10.1097/MOL.0b013e32834adac3. PMID- 21740971 OWN - NLM STAT- MEDLINE DCOM- 20120119 LR - 20150831 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 64 IP - 4 DP - 2011 Oct TI - Reaching LDL-c targets in high-risk patients requires high-efficacy cholesterol-lowering drugs in more than 50% of cases. The results of the CHECK study. PG - 393-6 LID - 10.1016/j.phrs.2011.06.017 [doi] AB - We estimated the need to use low-efficacy statins or high-efficacy statins or drug combinations to bring high- or very-high cardiovascular risk subjects to their LDL-c target, in a sample representative of the Italian adult population and according to the principles of reimbursement of hypercholesterolemic drugs currently used in Italy. The results allow us concluding that among high or very high cardiovascular risk patients about three patients out of five should be prescribed high-efficacy statins or drug combinations. The other two prescriptions might take into account lower-efficacy statins. If we also compute the values of HDL-c in these subjects--the large majority of which stands below the optimal values as suggested by International guidelines--we bring forward the need either to select specific statins able to increase the levels of these protective lipoproteins or to consider combination therapies of statins with fibrates or nicotinic acid. Our data might conceivably be applied to other low-cardiovascular risk countries and should be taken into account when defining the proportion of drugs with different efficacy and cost in the everyday clinical practice. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Poli, Andrea AU - Poli A AD - SEFAP, University of Milan, Milan, Italy. poli@nutrition-foundation.it FAU - Casula, Manuela AU - Casula M FAU - Tragni, Elena AU - Tragni E FAU - Brignoli, Ovidio AU - Brignoli O FAU - Filippi, Alessandro AU - Filippi A FAU - Cricelli, Claudio AU - Cricelli C FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article DEP - 20110628 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Aged MH - Cardiovascular Diseases/epidemiology/*prevention & control MH - Cholesterol, HDL/metabolism MH - Cholesterol, LDL/*metabolism MH - Cohort Studies MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Italy/epidemiology MH - Middle Aged EDAT- 2011/07/12 06:00 MHDA- 2012/01/20 06:00 CRDT- 2011/07/12 06:00 PHST- 2011/06/21 00:00 [received] PHST- 2011/06/21 00:00 [accepted] PHST- 2011/07/12 06:00 [entrez] PHST- 2011/07/12 06:00 [pubmed] PHST- 2012/01/20 06:00 [medline] AID - S1043-6618(11)00204-0 [pii] AID - 10.1016/j.phrs.2011.06.017 [doi] PST - ppublish SO - Pharmacol Res. 2011 Oct;64(4):393-6. doi: 10.1016/j.phrs.2011.06.017. Epub 2011 Jun 28. PMID- 21537834 OWN - NLM STAT- MEDLINE DCOM- 20111031 LR - 20111117 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 28 IP - 3 DP - 2011 Sep TI - Endothelin-1 does not impair insulin-induced angiogenesis in vitro. PG - 443-8 LID - 10.3892/ijmm.2011.689 [doi] AB - Endothelin-1 (ET-1) modulates several vascular functions and plays an important role in the pathogenesis of insulin resistance. However, its role in the pathogenesis of impaired angiogenesis observed under insulin resistance conditions is not known. In the present study, we addressed this issue by analyzing the effect of ET-1 in human umbilical vein endothelial cells (HUVEC) on i) insulin-induced phosphorylation of two protein kinases involved in angiogenesis, Akt and ERK1/2, and on ii) insulin-induced angiogenesis in two in vitro models, those of Matrigel and of fibroblast/endothelial co-culture. Both insulin (100 ng/ml) and ET-1 (10 nmol/l) dose-dependently increased the phosphorylation of Akt and ERK1/2. Pre-treatment with ET-1 did not suppress the insulin-induced Akt and ERK1/2 phosphorylation. In the two in vitro models of angiogenesis, ET-1 did not inhibit insulin-induced angiogenesis. From these data we conclude that in vitro, at the times and at the concentrations examined, ET-1 does not impair insulin-induced angiogenesis. FAU - Pellegatta, Fabio AU - Pellegatta F AD - Laboratory of Lipid Metabolism, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, I-20132 Milan, Italy. fabio.pellegatta@guest.unimi.it FAU - Brambilla, Claudia AU - Brambilla C FAU - Reduzzi, Alice AU - Reduzzi A FAU - Bragheri, Marta AU - Bragheri M FAU - Zerbini, Gianpaolo AU - Zerbini G FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110502 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Drug Combinations) RN - 0 (Endothelin-1) RN - 0 (Insulin) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 119978-18-6 (matrigel) RN - 9007-34-5 (Collagen) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Angiogenesis Inducing Agents/*metabolism MH - Cells, Cultured MH - Coculture Techniques MH - Collagen/metabolism MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Endothelial Cells/cytology/metabolism MH - Endothelin-1/*pharmacology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fibroblasts/cytology/metabolism MH - Humans MH - Insulin/*metabolism MH - Insulin Resistance MH - Laminin/metabolism MH - Neovascularization, Physiologic/*drug effects MH - Phosphorylation/drug effects MH - Proteoglycans/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Umbilical Veins/cytology EDAT- 2011/05/04 06:00 MHDA- 2011/11/01 06:00 CRDT- 2011/05/04 06:00 PHST- 2011/02/21 00:00 [received] PHST- 2011/04/08 00:00 [accepted] PHST- 2011/05/04 06:00 [entrez] PHST- 2011/05/04 06:00 [pubmed] PHST- 2011/11/01 06:00 [medline] AID - 10.3892/ijmm.2011.689 [doi] PST - ppublish SO - Int J Mol Med. 2011 Sep;28(3):443-8. doi: 10.3892/ijmm.2011.689. Epub 2011 May 2. PMID- 21592477 OWN - NLM STAT- MEDLINE DCOM- 20111207 LR - 20110729 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 217 IP - 2 DP - 2011 Aug TI - Cost-effectiveness of enhancing adherence to therapy with statins in the setting of primary cardiovascular prevention. Evidence from an empirical approach based on administrative databases. PG - 479-85 LID - 10.1016/j.atherosclerosis.2011.04.014 [doi] AB - AIM: To estimate the cost-effectiveness of enhancing adherence to statin therapy across a large population without signs of pre-existing cardiovascular disease. METHODS AND RESULTS: The cohort of 84,262 patients aged 40-79 years, resident in the Italian Lombardia Region, who were newly treated with statins during 2002-2003, was followed from index prescription until 2007. During follow-up the 1397 patients who experienced a hospitalization for ischemic heart disease (IHD) were identified (outcome). Adherence from index prescription until the date of hospitalization or censoring was measured by the proportion of days covered by the therapy with statins (PDC). Cost-effectiveness of enhancing adherence was measured through the incremental cost-effectiveness ratio (ICER). The robustness of findings was tested in a sensitivity analysis. Interventions to increase the average level of adherence from 45% (baseline) to 50% ("soft" intervention) or to 90% ("hard" intervention) reduced the number of patients who experience IHD (from 38.9 to 38.4 or 35.8 events every 10,000 person-year, respectively), and increased the cost for drug therapy (from 1326 to 1452 or 2626 thousand euros every 10,000 person-year, respectively). ICER ranged from 243 (95% CI: 230-259) to 413 (391-439) thousand euros every 10,000 person-year for the soft and hard interventions, respectively. CONCLUSIONS: Interventions aimed at enhancing adherence to statin therapy in the setting of primary cardiovascular prevention might offer important benefits in reducing the risk of cardiovascular outcome, but at a substantial cost. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Corrao, Giovanni AU - Corrao G AD - Department of Statistics, Unit of Biostatistics and Epidemiology, University of Milano-Bicocca, Milan, Italy. giovanni.corrao@unimib.it FAU - Scotti, Lorenza AU - Scotti L FAU - Zambon, Antonella AU - Zambon A FAU - Baio, Gianluca AU - Baio G FAU - Nicotra, Federica AU - Nicotra F FAU - Conti, Valentino AU - Conti V FAU - Capri, Stefano AU - Capri S FAU - Tragni, Elena AU - Tragni E FAU - Merlino, Luca AU - Merlino L FAU - Catapano, Alberico L AU - Catapano AL FAU - Mancia, Giuseppe AU - Mancia G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110422 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Adult MH - Aged MH - Cardiovascular Diseases/*economics/*prevention & control MH - Cost-Benefit Analysis MH - Data Mining MH - Drug Costs MH - Empirical Research MH - Evidence-Based Medicine MH - Female MH - *Health Care Costs MH - Health Services Research MH - Hospitalization/economics MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*economics/*therapeutic use MH - Italy MH - Male MH - *Medication Adherence MH - Middle Aged MH - Models, Economic MH - Primary Health Care/*economics MH - Primary Prevention/*economics MH - Proportional Hazards Models MH - Time Factors MH - Treatment Outcome EDAT- 2011/05/20 06:00 MHDA- 2011/12/13 00:00 CRDT- 2011/05/20 06:00 PHST- 2010/10/29 00:00 [received] PHST- 2011/04/12 00:00 [revised] PHST- 2011/04/12 00:00 [accepted] PHST- 2011/05/20 06:00 [entrez] PHST- 2011/05/20 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] AID - S0021-9150(11)00356-X [pii] AID - 10.1016/j.atherosclerosis.2011.04.014 [doi] PST - ppublish SO - Atherosclerosis. 2011 Aug;217(2):479-85. doi: 10.1016/j.atherosclerosis.2011.04.014. Epub 2011 Apr 22. PMID- 21743311 OWN - NLM STAT- MEDLINE DCOM- 20111024 LR - 20181201 IS - 1473-6535 (Electronic) IS - 0957-9672 (Linking) VI - 22 IP - 4 DP - 2011 Aug TI - Therapy and clinical trials: aggressive statin therapy versus combined and emerging approaches. PG - 324-5 LID - 10.1097/MOL.0b013e328348a513 [doi] FAU - Catapano, Alberico L AU - Catapano AL FAU - Norata, Giuseppe D AU - Norata GD FAU - Pirillo, Angela AU - Pirillo A LA - eng PT - Editorial PL - England TA - Curr Opin Lipidol JT - Current opinion in lipidology JID - 9010000 RN - 0 (Anticholesteremic Agents) RN - 0 (Fluorobenzenes) RN - 0 (Heptanoic Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Pyrroles) RN - 0 (Sulfonamides) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - A0JWA85V8F (Atorvastatin) RN - AGG2FN16EV (Simvastatin) SB - IM MH - Animals MH - Anticholesteremic Agents/*therapeutic use MH - Atherosclerosis/drug therapy/prevention & control MH - Atorvastatin MH - Clinical Trials as Topic MH - Dyslipidemias/*drug therapy MH - Fluorobenzenes/therapeutic use MH - Heptanoic Acids/therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors MH - Pyrimidines/therapeutic use MH - Pyrroles/therapeutic use MH - Rosuvastatin Calcium MH - Simvastatin/therapeutic use MH - Sulfonamides/therapeutic use EDAT- 2011/07/12 06:00 MHDA- 2011/10/25 06:00 CRDT- 2011/07/12 06:00 PHST- 2011/07/12 06:00 [entrez] PHST- 2011/07/12 06:00 [pubmed] PHST- 2011/10/25 06:00 [medline] AID - 10.1097/MOL.0b013e328348a513 [doi] AID - 00041433-201108000-00017 [pii] PST - ppublish SO - Curr Opin Lipidol. 2011 Aug;22(4):324-5. doi: 10.1097/MOL.0b013e328348a513. PMID- 21882396 OWN - NLM STAT- MEDLINE DCOM- 20120409 LR - 20131121 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 217 IP - 1 DP - 2011 Jul TI - ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). PG - 3-46 FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Science, University of Milan, Milano, Italy. Alberico.Catapano@unimi.it FAU - Reiner, Zeljko AU - Reiner Z FAU - De Backer, Guy AU - De Backer G FAU - Graham, Ian AU - Graham I FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Wiklund, Olov AU - Wiklund O FAU - Agewall, Stefan AU - Agewall S FAU - Alegria, Eduardo AU - Alegria E FAU - Chapman, M John AU - Chapman M FAU - Durrington, Paul AU - Durrington P FAU - Erdine, Serap AU - Erdine S FAU - Halcox, Julian AU - Halcox J FAU - Hobbs, Richard AU - Hobbs R FAU - Kjekshus, John AU - Kjekshus J FAU - Filardi, Pasquale Perrone AU - Filardi PP FAU - Riccardi, Gabriele AU - Riccardi G FAU - Storey, Robert F AU - Storey RF FAU - Wood, David AU - Wood D CN - European Society of Cardiology (ESC) CN - European Atherosclerosis Society (EAS) LA - eng PT - Guideline PT - Journal Article PT - Review PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoprotein(a)) RN - 97C5T2UQ7J (Cholesterol) SB - IM CIN - Atherosclerosis. 2012 Jan;220(1):42-4. PMID: 22093725 MH - Adult MH - Advisory Committees MH - Aged MH - Atherosclerosis/diagnosis/therapy MH - Cardiovascular Diseases/diagnosis/*therapy MH - Cholesterol/blood MH - Dyslipidemias/diagnosis/*therapy MH - Europe MH - Female MH - *Guidelines as Topic MH - Humans MH - Life Style MH - Lipoprotein(a)/blood MH - Male MH - Middle Aged MH - Risk MH - Sex Factors MH - Societies, Medical IR - Bax J FIR - Bax, Jeroen IR - Vahanian A FIR - Vahanian, Alec IR - Auricchio A FIR - Auricchio, Angelo IR - Baumgartner H FIR - Baumgartner, Helmut IR - Ceconi C FIR - Ceconi, Claudio IR - Dean V FIR - Dean, Veronica IR - Deaton C FIR - Deaton, Christi IR - Fagard R FIR - Fagard, Robert IR - Hoes A FIR - Hoes, Arno IR - Kearney P FIR - Kearney, Peter IR - Knuuti J FIR - Knuuti, Juhani IR - Kolh P FIR - Kolh, Philippe IR - McDonagh T FIR - McDonagh, Theresa IR - Moulin C FIR - Moulin, Cyril IR - Poldermans D FIR - Poldermans, Don IR - Popescu B FIR - Popescu, Bogdan IR - Reiner Z FIR - Reiner, Zeljko IR - Sechtem U FIR - Sechtem, Udo IR - Sirnes PA FIR - Sirnes, Per Anton IR - Tendera M FIR - Tendera, Michal IR - Torbicki A FIR - Torbicki, Adam IR - Vardas P FIR - Vardas, Panos IR - Widimsky P FIR - Widimsky, Petr IR - Windecker S FIR - Windecker, Stephan EDAT- 2011/09/02 06:00 MHDA- 2012/04/10 06:00 CRDT- 2011/09/02 06:00 PHST- 2011/09/02 06:00 [entrez] PHST- 2011/09/02 06:00 [pubmed] PHST- 2012/04/10 06:00 [medline] AID - S0021-9150(11)00548-X [pii] PST - ppublish SO - Atherosclerosis. 2011 Jul;217(1):3-46. PMID- 21723445 OWN - NLM STAT- MEDLINE DCOM- 20111213 LR - 20131121 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 217 Suppl 1 DP - 2011 Jul TI - ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). PG - S1-44 LID - 10.1016/j.atherosclerosis.2011.06.012 [doi] CN - Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) FAU - Catapano, Alberico L AU - Catapano AL FAU - Reiner, Zeljko AU - Reiner Z FAU - De Backer, Guy AU - De Backer G FAU - Graham, Ian AU - Graham I FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Wiklund, Olov AU - Wiklund O FAU - Agewall, Stefan AU - Agewall S FAU - Alegria, Eduardo AU - Alegria E FAU - Chapman, M John AU - Chapman MJ FAU - Durrington, Paul AU - Durrington P FAU - Erdine, Serap AU - Erdine S FAU - Halcox, Julian AU - Halcox J FAU - Hobbs, Richard AU - Hobbs R FAU - Kjekshus, John AU - Kjekshus J FAU - Perrone Filardi, Pasquale AU - Perrone Filardi P FAU - Riccardi, Gabriele AU - Riccardi G FAU - Storey, Robert F AU - Storey RF FAU - Wood, David AU - Wood D CN - ESC Committee for Practice Guidelines 2008-2010 and 2010-2012 Committees LA - eng PT - Journal Article PT - Review PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 97C5T2UQ7J (Cholesterol) SB - IM EIN - Atherosclerosis. 2011 Jul;217(1):2 MH - Adolescent MH - Adult MH - Aged MH - Atherosclerosis/*therapy MH - Cardiology/*methods MH - Cardiovascular Diseases/therapy MH - Child MH - Cholesterol/metabolism MH - Clinical Trials as Topic MH - Dyslipidemias/*therapy MH - Europe MH - Female MH - Genotype MH - Humans MH - Life Style MH - Lipids/blood MH - Lipoproteins/metabolism MH - Male MH - Middle Aged MH - *Practice Guidelines as Topic MH - Societies, Medical IR - Bax J FIR - Bax, Jeroen IR - Vahanian A FIR - Vahanian, Alec IR - Auricchio A FIR - Auricchio, Angelo IR - Baumgartner H FIR - Baumgartner, Helmut IR - Ceconi C FIR - Ceconi, Claudio IR - Dean V FIR - Dean, Veronica IR - Deaton C FIR - Deaton, Christi IR - Fagard R FIR - Fagard, Robert IR - Filippatos G FIR - Filippatos, Gerasimos IR - Funck-Brentano C FIR - Funck-Brentano, Christian IR - Hasdai D FIR - Hasdai, David IR - Hobbs R FIR - Hobbs, Richard IR - Hoes A FIR - Hoes, Arno IR - Kearney P FIR - Kearney, Peter IR - Knuuti J FIR - Knuuti, Juhani IR - Kolh P FIR - Kolh, Philippe IR - McDonagh T FIR - McDonagh, Theresa IR - Moulin C FIR - Moulin, Cyril IR - Poldermans D FIR - Poldermans, Don IR - Popescu B FIR - Popescu, Bogdan IR - Reiner Z FIR - Reiner, Zeljko IR - Sechtem U FIR - Sechtem, Udo IR - Sirnes PA FIR - Sirnes, Per Anton IR - Tendera M FIR - Tendera, Michal IR - Torbicki A FIR - Torbicki, Adam IR - Vardas P FIR - Vardas, Panos IR - Widimsky P FIR - Widimsky, Petr IR - Windecker S FIR - Windecker, Stephan EDAT- 2011/07/05 06:00 MHDA- 2011/12/14 06:00 CRDT- 2011/07/05 06:00 PHST- 2011/07/05 06:00 [entrez] PHST- 2011/07/05 06:00 [pubmed] PHST- 2011/12/14 06:00 [medline] AID - S0021-9150(11)00489-8 [pii] AID - 10.1016/j.atherosclerosis.2011.06.012 [doi] PST - ppublish SO - Atherosclerosis. 2011 Jul;217 Suppl 1:S1-44. doi: 10.1016/j.atherosclerosis.2011.06.012. PMID- 21722901 OWN - NLM STAT- MEDLINE DCOM- 20120409 LR - 20110718 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 217 IP - 1 DP - 2011 Jul TI - The new joint EAS/ESC guidelines for the management of dyslipidaemias. PG - 1 LID - 10.1016/j.atherosclerosis.2011.06.011 [doi] FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti, 9, 20133 Milano, Italy. Alberico.Catapano@unimi.it FAU - Chapman, John AU - Chapman J FAU - Wiklund, Olov AU - Wiklund O FAU - Taskinen, Marji-Riitta AU - Taskinen MR LA - eng PT - Journal Article DEP - 20110630 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) SB - IM MH - Atherosclerosis/diagnosis/therapy MH - Cardiovascular Diseases/diagnosis/*therapy MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Dyslipidemias/diagnosis/*therapy MH - Europe MH - *Guidelines as Topic MH - Humans MH - Risk MH - Societies, Medical EDAT- 2011/07/05 06:00 MHDA- 2012/04/10 06:00 CRDT- 2011/07/05 06:00 PHST- 2011/06/05 00:00 [received] PHST- 2011/06/06 00:00 [accepted] PHST- 2011/07/05 06:00 [entrez] PHST- 2011/07/05 06:00 [pubmed] PHST- 2012/04/10 06:00 [medline] AID - S0021-9150(11)00489-8 [pii] AID - 10.1016/j.atherosclerosis.2011.06.011 [doi] PST - ppublish SO - Atherosclerosis. 2011 Jul;217(1):1. doi: 10.1016/j.atherosclerosis.2011.06.011. Epub 2011 Jun 30. PMID- 21712404 OWN - NLM STAT- MEDLINE DCOM- 20120112 LR - 20120911 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 32 IP - 14 DP - 2011 Jul TI - ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). PG - 1769-818 LID - 10.1093/eurheartj/ehr158 [doi] AB - Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies' Task forces on CVD prevention in clinical practice.2 - 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat. CN - European Association for Cardiovascular Prevention & Rehabilitation AD - University Hospital Center Zagreb, School of Medicine, University of Zagreb, Salata 2, 10 000 Zagreb, Croatia. zreiner@kbc-zagreb.hr FAU - Reiner, Zeljko AU - Reiner Z FAU - Catapano, Alberico L AU - Catapano AL FAU - De Backer, Guy AU - De Backer G FAU - Graham, Ian AU - Graham I FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Wiklund, Olov AU - Wiklund O FAU - Agewall, Stefan AU - Agewall S FAU - Alegria, Eduardo AU - Alegria E FAU - Chapman, M John AU - Chapman MJ FAU - Durrington, Paul AU - Durrington P FAU - Erdine, Serap AU - Erdine S FAU - Halcox, Julian AU - Halcox J FAU - Hobbs, Richard AU - Hobbs R FAU - Kjekshus, John AU - Kjekshus J FAU - Filardi, Pasquale Perrone AU - Filardi PP FAU - Riccardi, Gabriele AU - Riccardi G FAU - Storey, Robert F AU - Storey RF FAU - Wood, David AU - Wood D CN - ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees LA - eng PT - Journal Article PT - Practice Guideline DEP - 20110628 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Dietary Fats) RN - 0 (Hypolipidemic Agents) SB - IM MH - Adult MH - Cardiovascular Diseases/*prevention & control MH - Child MH - Diet MH - Dietary Fats/administration & dosage MH - Dietary Supplements MH - Dyslipidemias/diet therapy/drug therapy/*prevention & control MH - Early Diagnosis MH - Energy Intake/physiology MH - Exercise MH - Female MH - Humans MH - Hypolipidemic Agents/therapeutic use MH - Kidney Failure, Chronic/complications MH - Life Style MH - Lipid Metabolism MH - Male MH - Patient Compliance MH - Primary Prevention/methods MH - Risk Assessment MH - Risk Factors MH - Secondary Prevention/methods MH - Specimen Handling/methods MH - Transplantation/adverse effects MH - Weight Loss IR - Bax J FIR - Bax, Jeroen IR - Vahanian A FIR - Vahanian, Alec IR - Auricchio A FIR - Auricchio, Angelo IR - Baumgartner H FIR - Baumgartner, Helmut IR - Ceconi C FIR - Ceconi, Claudio IR - Dean V FIR - Dean, Veronica IR - Deaton C FIR - Deaton, Christi IR - Fagard R FIR - Fagard, Robert IR - Filippatos G FIR - Filippatos, Gerasimos IR - Funck-Brentano C FIR - Funck-Brentano, Christian IR - Hasdai D FIR - Hasdai, David IR - Hobbs R FIR - Hobbs, Richard IR - Hoes A FIR - Hoes, Arno IR - Kearney P FIR - Kearney, Peter IR - Knuuti J FIR - Knuuti, Juhani IR - Kolh P FIR - Kolh, Philippe IR - McDonagh T FIR - McDonagh, Theresa IR - Moulin C FIR - Moulin, Cyril IR - Poldermans D FIR - Poldermans, Don IR - Popescu BA FIR - Popescu, Bogdan A IR - Reiner Z FIR - Reiner, Zeljko IR - Sechtem U FIR - Sechtem, Udo IR - Anton Sirnes P FIR - Anton Sirnes, Per IR - Tendera M FIR - Tendera, Michal IR - Torbicki A FIR - Torbicki, Adam IR - Vardas P FIR - Vardas, Panos IR - Widimsky P FIR - Widimsky, Petr IR - Windecker S FIR - Windecker, Stephan IR - Funck-Bretano C FIR - Funck-Bretano, Christian IR - Poldermans D FIR - Poldermans, Don IR - Berkenboom G FIR - Berkenboom, Guy IR - De Graaf J FIR - De Graaf, Jacqueline IR - Descamps O FIR - Descamps, Olivier IR - Gotcheva N FIR - Gotcheva, Nina IR - Griffith K FIR - Griffith, Kathryn IR - Guida GF FIR - Guida, Guido Francesco IR - Gulec S FIR - Gulec, Sadi IR - Henkin Y FIR - Henkin, Yaakov IR - Huber K FIR - Huber, Kurt IR - Kesaniemi YA FIR - Kesaniemi, Y Antero IR - Lekakis J FIR - Lekakis, John IR - Manolis AJ FIR - Manolis, Athanasios J IR - Marques-Vidal P FIR - Marques-Vidal, Pedro IR - Masana L FIR - Masana, Luis IR - McMurray J FIR - McMurray, John IR - Mendes M FIR - Mendes, Miguel IR - Pagava Z FIR - Pagava, Zurab IR - Pedersen T FIR - Pedersen, Terje IR - Prescott E FIR - Prescott, Eva IR - Rato Q FIR - Rato, Quiteria IR - Rosano G FIR - Rosano, Giuseppe IR - Sans S FIR - Sans, Susan IR - Stalenhoef A FIR - Stalenhoef, Anton IR - Tokgozoglu L FIR - Tokgozoglu, Lale IR - Viigimaa M FIR - Viigimaa, Margus IR - Wittekoek ME FIR - Wittekoek, M E IR - Zamorano JL FIR - Zamorano, Jose Luis EDAT- 2011/06/30 06:00 MHDA- 2012/01/13 06:00 CRDT- 2011/06/30 06:00 PHST- 2011/06/30 06:00 [entrez] PHST- 2011/06/30 06:00 [pubmed] PHST- 2012/01/13 06:00 [medline] AID - ehr158 [pii] AID - 10.1093/eurheartj/ehr158 [doi] PST - ppublish SO - Eur Heart J. 2011 Jul;32(14):1769-818. doi: 10.1093/eurheartj/ehr158. Epub 2011 Jun 28. PMID- 21531743 OWN - NLM STAT- MEDLINE DCOM- 20120106 LR - 20181113 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 32 IP - 11 DP - 2011 Jun TI - Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. PG - 1345-61 LID - 10.1093/eurheartj/ehr112 [doi] AB - Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (>/= 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. FAU - Chapman, M John AU - Chapman MJ AD - European Atherosclerosis Society, INSERM UMR-S939, Pitie-Salpetriere University Hospital, Paris 75651, France. john.chapman@upmc.fr FAU - Ginsberg, Henry N AU - Ginsberg HN FAU - Amarenco, Pierre AU - Amarenco P FAU - Andreotti, Felicita AU - Andreotti F FAU - Boren, Jan AU - Boren J FAU - Catapano, Alberico L AU - Catapano AL FAU - Descamps, Olivier S AU - Descamps OS FAU - Fisher, Edward AU - Fisher E FAU - Kovanen, Petri T AU - Kovanen PT FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA FAU - Lesnik, Philippe AU - Lesnik P FAU - Masana, Luis AU - Masana L FAU - Nordestgaard, Borge G AU - Nordestgaard BG FAU - Ray, Kausik K AU - Ray KK FAU - Reiner, Zeljko AU - Reiner Z FAU - Taskinen, Marja-Riitta AU - Taskinen MR FAU - Tokgozoglu, Lale AU - Tokgozoglu L FAU - Tybjaerg-Hansen, Anne AU - Tybjaerg-Hansen A FAU - Watts, Gerald F AU - Watts GF CN - European Atherosclerosis Society Consensus Panel LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20110429 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Cholesterol, HDL) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fibric Acids) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoproteins) RN - 0 (Triglycerides) RN - 0 (lipoprotein triglyceride) RN - 2679MF687A (Niacin) SB - IM MH - Cardiovascular Diseases/blood/*etiology/prevention & control MH - Cholesterol, HDL/*metabolism MH - Clinical Trials as Topic MH - Dyslipidemias/blood/*complications/prevention & control MH - Fatty Acids, Omega-3/therapeutic use MH - Fibric Acids/therapeutic use MH - Forecasting MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypolipidemic Agents/therapeutic use MH - Life Style MH - Lipid Metabolism MH - Lipoproteins/*metabolism MH - Niacin/therapeutic use MH - Risk Factors MH - Triglycerides/*metabolism PMC - PMC3105250 EDAT- 2011/05/03 06:00 MHDA- 2012/01/10 06:00 CRDT- 2011/05/03 06:00 PHST- 2011/05/03 06:00 [entrez] PHST- 2011/05/03 06:00 [pubmed] PHST- 2012/01/10 06:00 [medline] AID - ehr112 [pii] AID - 10.1093/eurheartj/ehr112 [doi] PST - ppublish SO - Eur Heart J. 2011 Jun;32(11):1345-61. doi: 10.1093/eurheartj/ehr112. Epub 2011 Apr 29. PMID- 21373679 OWN - NLM STAT- MEDLINE DCOM- 20110721 LR - 20110330 IS - 1477-0539 (Electronic) IS - 1477-0520 (Linking) VI - 9 IP - 8 DP - 2011 Apr 21 TI - Novel biotinylated bile acid amphiphiles: micellar aggregates formation and interaction with hepatocytes. PG - 2899-905 LID - 10.1039/c0ob00878h [doi] AB - Amphiphilic bile acids linked through an oligoethylene glycol to a biotin moiety were synthesized and shown to create micellar structures in aqueous environment, interact with avidin and be efficiently incorporated into hepatocyte cells, suggesting their potential as a drug delivery system against liver diseases. FAU - Rizzi, Luca AU - Rizzi L AD - Dipartimento di Scienze Farmaceutiche Pietro Pratesi, Universita degli Studi di Milano, 20133, Milano, Italy. FAU - Braschi, Marta AU - Braschi M FAU - Colombo, Miriam AU - Colombo M FAU - Vaiana, Nadia AU - Vaiana N FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Romeo, Sergio AU - Romeo S FAU - Prosperi, Davide AU - Prosperi D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110303 PL - England TA - Org Biomol Chem JT - Organic & biomolecular chemistry JID - 101154995 RN - 0 (Bile Acids and Salts) RN - 0 (Micelles) RN - 0 (Surface-Active Agents) SB - IM MH - Animals MH - Bile Acids and Salts/*chemistry MH - Biotinylation MH - Cell Line, Tumor MH - Hepatocytes/*chemistry MH - Mice MH - *Micelles MH - Molecular Structure MH - Surface-Active Agents/*chemistry EDAT- 2011/03/05 06:00 MHDA- 2011/07/22 06:00 CRDT- 2011/03/05 06:00 PHST- 2011/03/05 06:00 [entrez] PHST- 2011/03/05 06:00 [pubmed] PHST- 2011/07/22 06:00 [medline] AID - 10.1039/c0ob00878h [doi] PST - ppublish SO - Org Biomol Chem. 2011 Apr 21;9(8):2899-905. doi: 10.1039/c0ob00878h. Epub 2011 Mar 3. PMID- 21130457 OWN - NLM STAT- MEDLINE DCOM- 20110523 LR - 20110131 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 214 IP - 2 DP - 2011 Feb TI - Upregulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) by 15-lipoxygenase-modified LDL in endothelial cells. PG - 331-7 LID - 10.1016/j.atherosclerosis.2010.11.006 [doi] AB - OBJECTIVE: Lectin-like oxidized LDL receptor-1 (LOX-1), the endothelial receptor for OxLDL, is believed to be responsible for a number of OxLDL-induced effects in the endothelium. METHODS AND RESULTS: In the present study we showed that LDL modified by 15-lipoxygenase (15LO-LDL), a form of minimally modified lipoprotein, beside its ability to induce pro-inflammatory responses such as oxidative stress and the expression of adhesion molecules, significantly increases LOX-1 expression in endothelial cells, both at transcriptional and at protein level. Such effect is likely to be mediated by p38 MAPK and NF-kB pathways. We then permanently overexpressed LOX-1 in an endothelial cell line and showed that 15LO-LDL were a ligand for LOX-1, and that the interaction LOX-1/15LO-LDL upregulated ICAM-1 surface expression. CONCLUSION: Altogether these results indicate minimally modified LDL as a new inducer for LOX-1 expression and as a new ligand for LOX-1. CI - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. angela.pirillo@guest.unimi.it FAU - Reduzzi, Alice AU - Reduzzi A FAU - Ferri, Nicola AU - Ferri N FAU - Kuhn, Hartmut AU - Kuhn H FAU - Corsini, Alberto AU - Corsini A FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101113 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Ligands) RN - 0 (Lipoproteins, LDL) RN - 0 (NF-kappa B) RN - 0 (OLR1 protein, human) RN - 0 (RNA, Messenger) RN - 0 (Scavenger Receptors, Class E) RN - 0 (oxidized low density lipoprotein) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Arachidonate 15-Lipoxygenase/*metabolism MH - Cells, Cultured MH - Endothelial Cells/*metabolism MH - Gene Expression Regulation, Enzymologic MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Ligands MH - Lipoproteins, LDL/*metabolism MH - NF-kappa B/metabolism MH - Oxidative Stress MH - RNA, Messenger/metabolism MH - Rabbits MH - Scavenger Receptors, Class E/genetics/*metabolism MH - Time Factors MH - Transfection MH - Up-Regulation MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2010/12/07 06:00 MHDA- 2011/05/24 06:00 CRDT- 2010/12/07 06:00 PHST- 2010/06/18 00:00 [received] PHST- 2010/10/18 00:00 [revised] PHST- 2010/11/05 00:00 [accepted] PHST- 2010/12/07 06:00 [entrez] PHST- 2010/12/07 06:00 [pubmed] PHST- 2011/05/24 06:00 [medline] AID - S0021-9150(10)00905-6 [pii] AID - 10.1016/j.atherosclerosis.2010.11.006 [doi] PST - ppublish SO - Atherosclerosis. 2011 Feb;214(2):331-7. doi: 10.1016/j.atherosclerosis.2010.11.006. Epub 2010 Nov 13. PMID- 21094143 OWN - NLM STAT- MEDLINE DCOM- 20110120 LR - 20131121 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 403 IP - 3-4 DP - 2010 Dec 17 TI - Dual effect of hypochlorite in the modification of high density lipoproteins. PG - 447-51 LID - 10.1016/j.bbrc.2010.11.053 [doi] AB - HDL-cholesterol levels are inversely correlated to the risk of cardiovascular disease. In recent years the concept that not only the quantity, but also the quality of HDL is related to their atheroprotective function has gained momentum. In fact several studies have showed that HDL can shift their properties from anti-atherogenic to pro-atherogenic upon chemical or enzymatic "modification". However, not all kind of modifications affect the antiatherogenic properties of HDL. For example, tyrosylation of HDL improves its ability to remove cholesterol from cultured cells and inhibits mice atherosclerotic lesion formation; oxidation of HDL(3) with 15-lipoxygenase or with copper ions for short time induce the formation of pre-beta-migrating particles that are highly effective as cholesterol acceptors from lipid laden cells. Myeloperoxidase modifies HDL and apoA-I and reduces their ability to promote ABCA1-mediated cholesterol efflux. In the present study we show that modification with low concentration HOCl (a myeloperoxidase product) induces the formation of pre-beta-migrating particles, thus improving the function of HDL in the reverse cholesterol transport, without affecting the anti-inflammatory activity. At higher HOCl concentration, pre-beta-migrating particles were not detectable and the anti-inflammatory properties of HDL were lost. These findings suggest that during early phases of inflammation, when a low HOCl concentration is generated, changes in HDL occur that increase their ability to remove cholesterol and sparing anti-inflammatory properties; later during acute inflammation, when higher HOCl concentration are present changes in HDL occur that severely decrease their ability to remove cholesterol from macrophages and to protect endothelial cells from pro-inflammatory stimuli. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Pirillo, Angela AU - Pirillo A AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. angela.pirillo@guest.unimi.it FAU - Uboldi, Patrizia AU - Uboldi P FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101119 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 712K4CDC10 (Hypochlorous Acid) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Cell Line MH - Cholesterol/*metabolism MH - Hypochlorous Acid/*metabolism/pharmacology MH - Inflammation/*metabolism MH - Lipoproteins, HDL/*metabolism MH - Lipoproteins, HDL3/metabolism MH - Macrophages/drug effects/metabolism MH - Mice EDAT- 2010/11/26 06:00 MHDA- 2011/01/21 06:00 CRDT- 2010/11/25 06:00 PHST- 2010/11/04 00:00 [received] PHST- 2010/11/14 00:00 [accepted] PHST- 2010/11/25 06:00 [entrez] PHST- 2010/11/26 06:00 [pubmed] PHST- 2011/01/21 06:00 [medline] AID - S0006-291X(10)02112-1 [pii] AID - 10.1016/j.bbrc.2010.11.053 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2010 Dec 17;403(3-4):447-51. doi: 10.1016/j.bbrc.2010.11.053. Epub 2010 Nov 19. PMID- 21193152 OWN - NLM STAT- MEDLINE DCOM- 20110519 LR - 20121115 IS - 1878-5050 (Electronic) IS - 1567-5688 (Linking) VI - 11 IP - 3 DP - 2010 Dec TI - Pitavastatin - pharmacological profile from early phase studies. PG - 3-7 LID - 10.1016/S1567-5688(10)71063-1 [doi] AB - Pitavastatin has been designed as a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor with a novel cyclopropyl moiety that results in several differences compared to other statins. These include effective inhibition of cholesterol synthesis and increased lipoprotein lipase expression at lower doses than other statins, and significant high-density lipoprotein-cholesterol and apolipoprotein A1-elevating activity that persists with time. The safety, tolerability and pharmacokinetics of pitavastatin and its major metabolite, pitavastatin lactone, have been investigated in a variety of patient groups with similar results, which suggests dosage adjustments are not required for gender, age or race. In healthy subjects, pitavastatin is well tolerated at the approved doses with no serious adverse events. The bioavailability of pitavastatin is, at 60%, higher than that of any other statin and the majority of the bioavailable fraction of an oral dose is excreted unchanged in the bile. The entero-hepatic circulation of unchanged drug contributes to the prolonged duration of action and allows once-daily, any-time dosing. Pitavastatin is only slightly metabolised by cytochrome P450 (CYP) 2C9 and not at all by CYP3A4. Neither pitavastatin nor its lactone form, have inhibitory effects on CYP, and CYP3A4 inhibitors have no effect on pitavastatin concentrations. Moreover, P-glycoprotein-mediated transport does not play a major role in the drug's disposition and pitavastatin does not inhibit P-glycoprotein activity. Pitavastatin is transported into the liver by several hepatic transporters but OATP1B1 inhibitors have relatively little effect on plasma concentrations compared with other statins. In general, interactions, except with multi-transporter inhibitors like ciclosporin, are not clinically significant. Consequently, pitavastatin has minimal drug-food and drug-drug interactions making it a treatment option in the large group of dyslipidaemic people that require multidrug therapy. CI - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Catapano, Alberico L AU - Catapano AL AD - Centre for the Study of Atherosclerosis, Department of Pharmacological Sciences, University of Milan, and IRCSS Multimedica, Sesto S. Giovanni, Milan, Italy. Alberico.catapano@unimi.it LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Atheroscler Suppl JT - Atherosclerosis. Supplements JID - 100973461 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Quinolines) RN - M5681Q5F9P (pitavastatin) SB - IM MH - Drug Interactions MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics/*pharmacology MH - Quinolines/pharmacokinetics/*pharmacology EDAT- 2011/01/05 06:00 MHDA- 2011/05/20 06:00 CRDT- 2011/01/04 06:00 PHST- 2011/01/04 06:00 [entrez] PHST- 2011/01/05 06:00 [pubmed] PHST- 2011/05/20 06:00 [medline] AID - S1567-5688(10)71063-1 [pii] AID - 10.1016/S1567-5688(10)71063-1 [doi] PST - ppublish SO - Atheroscler Suppl. 2010 Dec;11(3):3-7. doi: 10.1016/S1567-5688(10)71063-1. PMID- 20308908 OWN - NLM STAT- MEDLINE DCOM- 20110201 LR - 20151119 IS - 1741-8275 (Electronic) IS - 1741-8267 (Linking) VI - 17 IP - 5 DP - 2010 Oct TI - Blood pressure and antihypertensive therapy according to the global cardiovascular risk level in Italy: the CHECK Study. PG - 562-8 LID - 10.1097/HJR.0b013e328338a4c6 [doi] AB - BACKGROUND: Elevated blood pressure (BP) is one of the most important modifiable risk factors for cardiovascular diseases. In this study we assessed the excess of cardiovascular risk attributable to high BP and antihypertensive treatment in a sample of Italian patients enrolled by the 'Cholesterol and Health: Education, Control and Knowledge' (CHECK) study. METHODS: CHECK is a large, cross-sectional epidemiological study, which randomly enrolled patients aged 40-79 years from 425 Italian General Practices from March 2002 to April 2004. Among 5731 patients enrolled in the study [49.6% men, mean age (standard deviation) 57.7 (10.3) years], 723 (12.6%) had 'optimal' BP, 1496 (26.1%) had 'high normal' BP, and 1942 (33.9%) were hypertensive. RESULTS: According to the European Guidelines stratification of the cardiovascular risk-excess attributable to high BP, 34.7% of the sample had a low added risk and 53.2% had a moderate-to-very high added risk. The pharmacological therapy was prescribed in 22.3, 43.9, 61.4, and 76.9% of the patients with low, moderate, high, and very high added risk, respectively. CONCLUSION: Overall dietary and drug therapies are under prescribed, as most of the treated patients would require two additional antihypertensive drugs to meet the recommended BP target. This effort could provide significant individual benefit to moderate/high-risk patients. FAU - Filippi, Alessandro AU - Filippi A AD - Italian Society of General Medicine (SIMG), Florence, Italy. FAU - Casula, Manuela AU - Casula M FAU - Tragni, Elena AU - Tragni E FAU - Brignoli, Ovidio AU - Brignoli O FAU - Cricelli, Claudio AU - Cricelli C FAU - Poli, Andrea AU - Poli A FAU - Catapano, Alberico Luigi AU - Catapano AL CN - CHECK Study Group LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Cardiovasc Prev Rehabil JT - European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology JID - 101192000 RN - 0 (Antihypertensive Agents) SB - IM MH - Adult MH - Aged MH - Antihypertensive Agents/*therapeutic use MH - Blood Pressure/*drug effects MH - Cardiovascular Diseases/etiology/physiopathology/*prevention & control MH - Cross-Sectional Studies MH - Drug Prescriptions MH - Drug Utilization MH - Female MH - General Practice MH - Guideline Adherence MH - Humans MH - Hypertension/complications/*drug therapy/physiopathology MH - Italy MH - Male MH - Middle Aged MH - Odds Ratio MH - Practice Guidelines as Topic MH - *Practice Patterns, Physicians' MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome EDAT- 2010/03/24 06:00 MHDA- 2011/02/02 06:00 CRDT- 2010/03/24 06:00 PHST- 2010/03/24 06:00 [entrez] PHST- 2010/03/24 06:00 [pubmed] PHST- 2011/02/02 06:00 [medline] AID - 10.1097/HJR.0b013e328338a4c6 [doi] PST - ppublish SO - Eur J Cardiovasc Prev Rehabil. 2010 Oct;17(5):562-8. doi: 10.1097/HJR.0b013e328338a4c6. PMID- 20685842 OWN - NLM STAT- MEDLINE DCOM- 20110303 LR - 20100924 IS - 1460-2393 (Electronic) IS - 1460-2393 (Linking) VI - 103 IP - 10 DP - 2010 Oct TI - Barriers to cardiovascular disease risk scoring and primary prevention in Europe. PG - 727-39 LID - 10.1093/qjmed/hcq122 [doi] AB - The prevalence and burden of cardiovascular disease (CVD) is high, and it remains the leading cause of death worldwide. Unfortunately, many individuals who are at high risk for CVD are not recognized and/or treated. Therefore, programs are available to ensure individuals at risk for CVD are identified through appropriate risk classification and offered optimal preventative interventions. The use of algorithms to determine a global risk score may help to achieve these goals. Such global risk-scoring algorithms takes into account the synergistic effects between individual risk factors, placing increases in individual risk factors into context relative to the overall disease, allowing for a continuum of disease risk to be expressed, and identifying patients most likely to derive benefit from an intervention. The predictive value of risk scoring such as using the Framingham equation is reasonable, analogous to cervical screening, with area under the receiver operated characteristic curve a little over 70%. However, limitations do exist, and as they are identified adjustments can be made to the global risk-scoring algorithms. Limitations include patient-specific issues, such as variations in lifetime risk level, ethnicity or socio-economic strata, and algorithm-specific issues, such as discrepancies between different algorithms arising from varying risk factors evaluated. The use of currently developed algorithms is low in general practice, in part, because of the belief that the assessment may oversimplify the risk and/or lead to medication overuse. Additional hindrances to the use of risk scoring include government or local health policy, patient compliance issues and lack of time. A thorough, easy-to-use, and standardized tool for risk estimation would allow for improvements in the primary prevention of CVD. FAU - Hobbs, F D R AU - Hobbs FD AD - Primary Care Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK. f.d.r.hobbs@bham.ac.uk FAU - Jukema, J W AU - Jukema JW FAU - Da Silva, P M AU - Da Silva PM FAU - McCormack, T AU - McCormack T FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20100804 PL - England TA - QJM JT - QJM : monthly journal of the Association of Physicians JID - 9438285 SB - IM MH - Age Factors MH - *Algorithms MH - Cardiovascular Diseases/*diagnosis/epidemiology/prevention & control MH - Europe/epidemiology MH - Female MH - General Practice MH - Humans MH - Male MH - Primary Prevention MH - Risk Assessment/methods EDAT- 2010/08/06 06:00 MHDA- 2011/03/04 06:00 CRDT- 2010/08/06 06:00 PHST- 2010/08/06 06:00 [entrez] PHST- 2010/08/06 06:00 [pubmed] PHST- 2011/03/04 06:00 [medline] AID - hcq122 [pii] AID - 10.1093/qjmed/hcq122 [doi] PST - ppublish SO - QJM. 2010 Oct;103(10):727-39. doi: 10.1093/qjmed/hcq122. Epub 2010 Aug 4. PMID- 20539016 OWN - NLM STAT- MEDLINE DCOM- 20100920 LR - 20161125 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 30 IP - 9 DP - 2010 Sep TI - Circulating CD4+CD25hiCD127lo regulatory T-Cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis. PG - 1832-41 LID - 10.1161/ATVBAHA.110.206813 [doi] AB - OBJECTIVE: Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries. METHODS AND RESULTS: We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3(+)CD4(+)CD25(high)CD127(low)) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (n=65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients). CONCLUSIONS: The results suggest that determination of circulating Treg-cell levels based on flow cytometry or mRNA assessment is not a useful indicator of the extent or severity of atherosclerosis. FAU - Ammirati, Enrico AU - Ammirati E AD - Clinical Cardiovascular Biology Research Centre, San Raffaele Scientific Institute and the Universita Vita-Salute San Raffaele, Via Olgettina 58, 20132 Milan, Italy. ammirati.enrico@hsr.it FAU - Cianflone, Domenico AU - Cianflone D FAU - Banfi, Michela AU - Banfi M FAU - Vecchio, Viviana AU - Vecchio V FAU - Palini, Alessio AU - Palini A FAU - De Metrio, Monica AU - De Metrio M FAU - Marenzi, Giancarlo AU - Marenzi G FAU - Panciroli, Claudio AU - Panciroli C FAU - Tumminello, Gabriele AU - Tumminello G FAU - Anzuini, Angelo AU - Anzuini A FAU - Palloshi, Altin AU - Palloshi A FAU - Grigore, Liliana AU - Grigore L FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Tramontana, Simona AU - Tramontana S FAU - Tavano, Davide AU - Tavano D FAU - Airoldi, Flavio AU - Airoldi F FAU - Manfredi, Angelo A AU - Manfredi AA FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100610 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Biomarkers) RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (IL10 protein, human) RN - 0 (IL6 protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Interleukin-7 Receptor alpha Subunit) RN - 0 (RNA, Messenger) RN - 130068-27-8 (Interleukin-10) SB - IM CIN - Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1679-81. PMID: 20720192 MH - Acute Coronary Syndrome/immunology MH - Aged MH - Angina Pectoris/immunology MH - Biomarkers/blood MH - CD4 Lymphocyte Count MH - Carotid Artery Diseases/diagnostic imaging/*immunology MH - Case-Control Studies MH - Coronary Angiography MH - Coronary Artery Disease/complications/diagnostic imaging/*immunology MH - Female MH - Flow Cytometry MH - Forkhead Transcription Factors/genetics MH - Humans MH - Immunophenotyping MH - Inflammation Mediators/blood MH - Interleukin-10/blood/genetics MH - Interleukin-6/blood MH - Interleukin-7 Receptor alpha Subunit/*blood MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Prospective Studies MH - RNA, Messenger/blood MH - Severity of Illness Index MH - T-Lymphocytes, Regulatory/*immunology MH - Ultrasonography EDAT- 2010/06/12 06:00 MHDA- 2010/09/21 06:00 CRDT- 2010/06/12 06:00 PHST- 2010/06/12 06:00 [entrez] PHST- 2010/06/12 06:00 [pubmed] PHST- 2010/09/21 06:00 [medline] AID - ATVBAHA.110.206813 [pii] AID - 10.1161/ATVBAHA.110.206813 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1832-41. doi: 10.1161/ATVBAHA.110.206813. Epub 2010 Jun 10. PMID- 20557886 OWN - NLM STAT- MEDLINE DCOM- 20101228 LR - 20100903 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 212 IP - 1 DP - 2010 Sep TI - The androgen derivative 5alpha-androstane-3beta,17beta-diol inhibits tumor necrosis factor alpha and lipopolysaccharide induced inflammatory response in human endothelial cells and in mice aorta. PG - 100-6 LID - 10.1016/j.atherosclerosis.2010.05.015 [doi] AB - BACKGROUND: An increasing body of evidence suggests that testosterone may exert beneficial effects against the development of atherosclerosis. These effects are thought to be the consequence of its conversion into estradiol and the activation of the estrogen receptors; however a direct role of androgens, such as dihydrotestosterone, has also been proposed. More recently, it has been shown that the transformation of the dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) and 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), generates two molecules unable to bind the androgen receptor, but with a high affinity for the estrogen receptors (ERs) in particular the beta isoform. As the actions of testosterone may result from the balance between androgenic and estrogenic molecules originating from its catabolism, we investigated the effects of the 3beta-Adiol on inflammatory responses in vitro in human endothelial cells and ex vivo in mice aortas. METHODS AND RESULTS: 3beta-Adiol reverts the pro-inflammatory gene expression pattern induced by TNF-alpha in HUVECs as determined by a cDNA microrray approach. Q-real-time PCR and protein array approaches confirmed that TNF-alpha-induced ICAM-1, VCAM-1 and ELAM-1 as well as MCP-1 and IL-6 induction was affected upon 3beta-Adiol pre-incubation. ICI 182780, an estrogen receptor antagonist and R,R-THC, an estrogen receptor beta antagonist, counteracted the effect of 3beta-Adiol while bicalutamide, an androgen receptor antagonist, had minor effects. 3beta-Adiol exerted a similar action on macrophages. Finally in castrated male mice, 3beta-Adiol significantly counteracted the LPS mediated mRNA induction of IL-6, ELAM-1and PECAM-1 in the aortas. CONCLUSION: 3beta-Adiol reverts in vitro the TNF-alpha and LPS induced pro-inflammatory activation of endothelial cells and macrophages. 3beta-Adiol in vivo modulates the inflammatory response induced by LPS in the arterial vascular wall. CI - Copyright 2010 Elsevier Ireland Ltd. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, Italy. Danilo.Norata@unimi.it FAU - Cattaneo, Paola AU - Cattaneo P FAU - Poletti, Angelo AU - Poletti A FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100519 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Androgen Antagonists) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Estrogen Antagonists) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 25126-76-5 (Androstane-3,17-diol) SB - IM MH - Androgen Antagonists/pharmacology MH - Androstane-3,17-diol/*administration & dosage MH - Animals MH - Anti-Inflammatory Agents/*administration & dosage MH - Aorta/*drug effects/immunology MH - Endothelial Cells/*drug effects/immunology MH - Estrogen Antagonists/pharmacology MH - Gene Expression Profiling/methods MH - Gene Expression Regulation/drug effects MH - Humans MH - Inflammation/genetics/immunology/*prevention & control MH - Inflammation Mediators/*metabolism MH - Lipopolysaccharides/*pharmacology MH - Macrophages/drug effects/immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Oligonucleotide Array Sequence Analysis MH - Orchiectomy MH - Protein Array Analysis MH - RNA, Messenger/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/*metabolism MH - U937 Cells EDAT- 2010/06/19 06:00 MHDA- 2010/12/29 06:00 CRDT- 2010/06/19 06:00 PHST- 2009/12/22 00:00 [received] PHST- 2010/05/10 00:00 [revised] PHST- 2010/05/10 00:00 [accepted] PHST- 2010/06/19 06:00 [entrez] PHST- 2010/06/19 06:00 [pubmed] PHST- 2010/12/29 06:00 [medline] AID - S0021-9150(10)00393-X [pii] AID - 10.1016/j.atherosclerosis.2010.05.015 [doi] PST - ppublish SO - Atherosclerosis. 2010 Sep;212(1):100-6. doi: 10.1016/j.atherosclerosis.2010.05.015. Epub 2010 May 19. PMID- 20625262 OWN - NLM STAT- MEDLINE DCOM- 20101008 LR - 20151119 IS - 1473-6535 (Electronic) IS - 0957-9672 (Linking) VI - 21 IP - 4 DP - 2010 Aug TI - Therapy and clinical trials: new insights. PG - 394-5 LID - 10.1097/MOL.0b013e32833c2260 [doi] FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Grigore, Liliana AU - Grigore L FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Editorial PL - England TA - Curr Opin Lipidol JT - Current opinion in lipidology JID - 9010000 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 2679MF687A (Niacin) SB - IM MH - Clinical Trials as Topic MH - Diabetes Mellitus/*drug therapy MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypolipidemic Agents/therapeutic use MH - Niacin/therapeutic use EDAT- 2010/07/14 06:00 MHDA- 2010/10/12 06:00 CRDT- 2010/07/14 06:00 PHST- 2010/07/14 06:00 [entrez] PHST- 2010/07/14 06:00 [pubmed] PHST- 2010/10/12 06:00 [medline] AID - 10.1097/MOL.0b013e32833c2260 [doi] AID - 00041433-201008000-00019 [pii] PST - ppublish SO - Curr Opin Lipidol. 2010 Aug;21(4):394-5. doi: 10.1097/MOL.0b013e32833c2260. PMID- 20435179 OWN - NLM STAT- MEDLINE DCOM- 20100524 LR - 20181113 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 159 IP - 5 DP - 2010 May TI - Individual progression of carotid intima media thickness as a surrogate for vascular risk (PROG-IMT): Rationale and design of a meta-analysis project. PG - 730-736.e2 LID - 10.1016/j.ahj.2010.02.008 [doi] AB - Carotid intima media thickness (IMT) progression is increasingly used as a surrogate for vascular risk. This use is supported by data from a few clinical trials investigating statins, but established criteria of surrogacy are only partially fulfilled. To provide a valid basis for the use of IMT progression as a study end point, we are performing a 3-step meta-analysis project based on individual participant data. Objectives of the 3 successive stages are to investigate (1) whether IMT progression prospectively predicts myocardial infarction, stroke, or death in population-based samples; (2) whether it does so in prevalent disease cohorts; and (3) whether interventions affecting IMT progression predict a therapeutic effect on clinical end points. Recruitment strategies, inclusion criteria, and estimates of the expected numbers of eligible studies are presented along with a detailed analysis plan. CI - 2010 Mosby, Inc. All rights reserved. FAU - Lorenz, Matthias W AU - Lorenz MW AD - Department of Neurology, University Hospital, Goethe-University, Frankfurt am Main, Germany. matthias.lorenz@em.uni-frankfurt.de FAU - Bickel, Horst AU - Bickel H FAU - Bots, Michiel L AU - Bots ML FAU - Breteler, Monique M B AU - Breteler MM FAU - Catapano, Alberico L AU - Catapano AL FAU - Desvarieux, Moise AU - Desvarieux M FAU - Hedblad, Bo AU - Hedblad B FAU - Iglseder, Bernhard AU - Iglseder B FAU - Johnsen, Stein Harald AU - Johnsen SH FAU - Juraska, Michal AU - Juraska M FAU - Kiechl, Stefan AU - Kiechl S FAU - Mathiesen, Ellisiv B AU - Mathiesen EB FAU - Norata, Giuseppe D AU - Norata GD FAU - Grigore, Liliana AU - Grigore L FAU - Polak, Joseph AU - Polak J FAU - Poppert, Holger AU - Poppert H FAU - Rosvall, Maria AU - Rosvall M FAU - Rundek, Tatjana AU - Rundek T FAU - Sacco, Ralph L AU - Sacco RL FAU - Sander, Dirk AU - Sander D FAU - Sitzer, Matthias AU - Sitzer M FAU - Steinmetz, Helmuth AU - Steinmetz H FAU - Stensland, Eva AU - Stensland E FAU - Willeit, Johann AU - Willeit J FAU - Witteman, Jacqueline AU - Witteman J FAU - Yanez, David AU - Yanez D FAU - Thompson, Simon G AU - Thompson SG CN - PROG-IMT Study Group LA - eng GR - MC_U105260792/Medical Research Council/United Kingdom GR - R01 DE013094/DE/NIDCR NIH HHS/United States GR - RG/08/014/24067/British Heart Foundation/United Kingdom PT - Journal Article PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 SB - AIM SB - IM MH - Carotid Arteries/*pathology MH - Carotid Artery Diseases/epidemiology MH - Humans MH - *Meta-Analysis as Topic MH - Multicenter Studies as Topic MH - Myocardial Infarction/epidemiology MH - Predictive Value of Tests MH - Research Design MH - Risk Assessment/*methods MH - Stroke/epidemiology MH - Tunica Intima/*pathology PMC - PMC3600980 MID - NIHMS446372 IR - Bickel H FIR - Bickel, Horst IR - Bots ML FIR - Bots, Michiel L IR - Breteler M FIR - Breteler, Monique IR - Catapano AL FIR - Catapano, Alberico L IR - Desvarieux M FIR - Desvarieux, Moise IR - Grigore L FIR - Grigore, Liliana IR - Hedblad B FIR - Hedblad, Bo IR - Iglseder B FIR - Iglseder, Bernhard IR - Johnsen SH FIR - Johnsen, Stein Harald IR - Juraska M FIR - Juraska, Michal IR - Kiechl S FIR - Kiechl, Stefan IR - Lorenz MW FIR - Lorenz, Matthias W IR - Mathiesen E FIR - Mathiesen, Ellisiv IR - Norata GD FIR - Norata, Giuseppe Danilo IR - Polak J FIR - Polak, Joseph IR - Poppert H FIR - Poppert, Holger IR - Rosvall M FIR - Rosvall, Maria IR - Rundek T FIR - Rundek, Tatjana IR - Sacco RL FIR - Sacco, Ralph L IR - Sander D FIR - Sander, Dirk IR - Sitzer M FIR - Sitzer, Matthias IR - Steinmetz H FIR - Steinmetz, Helmuth IR - Stensland E FIR - Stensland, Eva IR - Thompson SG FIR - Thompson, Simon G IR - Willeit J FIR - Willeit, Johann IR - Witteman J FIR - Witteman, Jacqueline IR - Yanez D FIR - Yanez, David IR - Sitzer M FIR - Sitzer, Matthias IR - Thompson SG FIR - Thompson, Simon G IR - Lorenz MW FIR - Lorenz, Matthias W EDAT- 2010/05/04 06:00 MHDA- 2010/05/25 06:00 CRDT- 2010/05/04 06:00 PHST- 2009/10/01 00:00 [received] PHST- 2010/02/02 00:00 [accepted] PHST- 2010/05/04 06:00 [entrez] PHST- 2010/05/04 06:00 [pubmed] PHST- 2010/05/25 06:00 [medline] AID - S0002-8703(10)00149-3 [pii] AID - 10.1016/j.ahj.2010.02.008 [doi] PST - ppublish SO - Am Heart J. 2010 May;159(5):730-736.e2. doi: 10.1016/j.ahj.2010.02.008. PMID- 19945109 OWN - NLM STAT- MEDLINE DCOM- 20100816 LR - 20131121 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 210 IP - 1 DP - 2010 May TI - Increased atherosclerosis and vascular inflammation in APP transgenic mice with apolipoprotein E deficiency. PG - 78-87 LID - 10.1016/j.atherosclerosis.2009.10.040 [doi] AB - OBJECTIVE: Atherosclerosis is associated with Alzheimer's disease (AD) in humans, but the nature of this link is still elusive. Aim of this study was to investigate aortic atherosclerosis development in a mouse model with central nervous system (CNS) restricted beta-amyloid precursor protein (APP) overexpression. METHODS AND RESULTS: APP23 mice, overexpressing the Swedish mutated human APP selectively in the brain, were crossed with mice lacking apolipoprotein E (ApoE KO). Nine weeks old mice were fed a western type diet for eight weeks, then atherosclerotic lesions, aortic wall and cortical tissues gene expression and beta-amyloid (Abeta) deposition were evaluated. Compared with ApoE KO, APP23/ApoE KO mice developed larger aortic atherosclerotic lesions and showed significantly increased expression of MCP-1, IL-6, ICAM-1 and MTPase 6, a marker of oxidative stress in the vascular wall. Of note brain limited APP synthesis was associated with an increased microglia and brain endothelial cells activation, in spite of the absence of beta-amyloid deposits in the brain or alteration in the levels of oxidized metabolites of cholesterol such as 4-cholesten-3-one. CONCLUSION: Our study suggests that the vascular pro-inflammatory effects of CNS-localised APP overexpression lead to atherogenesis before parenchymal Abeta deposition and neuronal dysfunction. CI - Copyright 2009 Elsevier Ireland Ltd. All rights reserved. FAU - Tibolla, G AU - Tibolla G AD - Department of Pharmacological Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Norata, G D AU - Norata GD FAU - Meda, C AU - Meda C FAU - Arnaboldi, L AU - Arnaboldi L FAU - Uboldi, P AU - Uboldi P FAU - Piazza, F AU - Piazza F FAU - Ferrarese, C AU - Ferrarese C FAU - Corsini, A AU - Corsini A FAU - Maggi, A AU - Maggi A FAU - Vegeto, E AU - Vegeto E FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091110 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Apolipoproteins E) RN - 0 (Cholestenones) RN - 0 (Interleukin-6) RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 0 (lipoprotein cholesterol) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 601-57-0 (cholest-4-en-3-one) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Amyloid beta-Peptides/analysis MH - Amyloid beta-Protein Precursor/*analysis MH - Animals MH - Aorta/*pathology MH - Aortic Diseases/*pathology MH - Apolipoproteins E/*deficiency MH - Atherosclerosis/etiology/*pathology MH - *Brain Chemistry MH - Cholestenones/analysis MH - Cholesterol/analysis/blood MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Expression MH - Immunohistochemistry MH - Inflammation MH - Intercellular Adhesion Molecule-1/analysis MH - Interleukin-6/analysis MH - Lipids/blood MH - Lipoproteins/blood MH - Male MH - Mice MH - Mice, Transgenic MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2009/12/01 06:00 MHDA- 2010/08/17 06:00 CRDT- 2009/12/01 06:00 PHST- 2009/04/17 00:00 [received] PHST- 2009/10/29 00:00 [revised] PHST- 2009/10/30 00:00 [accepted] PHST- 2009/12/01 06:00 [entrez] PHST- 2009/12/01 06:00 [pubmed] PHST- 2010/08/17 06:00 [medline] AID - S0021-9150(09)00914-9 [pii] AID - 10.1016/j.atherosclerosis.2009.10.040 [doi] PST - ppublish SO - Atherosclerosis. 2010 May;210(1):78-87. doi: 10.1016/j.atherosclerosis.2009.10.040. Epub 2009 Nov 10. PMID- 20206788 OWN - NLM STAT- MEDLINE DCOM- 20100528 LR - 20100308 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 32 IP - 2 DP - 2010 Feb TI - Results of a retrospective database analysis of adherence to statin therapy and risk of nonfatal ischemic heart disease in daily clinical practice in Italy. PG - 300-10 LID - 10.1016/j.clinthera.2010.02.004 [doi] AB - BACKGROUND: Previous studies have reported that statin use was associated with reductions in cardiovascular morbidity and mortality among patients with dyslipidemia, even without established cardiovascular disease. However, inadequate adherence may reduce statins' protective effects. OBJECTIVE: The aim of this work was to investigate whether an association exists between statin adherence when used as primary prevention and risk of subsequent ischemic heart disease (IHD). METHODS: People aged >or=18 years who were residents of Italy's Lombardy region and were newly treated with statins in 2002 to 2003 were assessed as part of a retrospective analysis of data from a health services database. Patients who were hospitalized for IHD during this period were identified with hospital discharge information from a health-services database; IHD-related hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes for acute myocardial infarction (410), acute and subacute forms of IHD (411), and/or codes concerning coronary revascularization (36.0-36.9). Four groups of patients were excluded: those with >or=1 lipid-lowering drug within 2 years before the index prescription (to limit the sample to treatment initiators); those who had been hospitalized for cardiovascular disease or had used medications for IHD or heart failure within 2 years before the index date (to limit the study to primary prevention); those who did not have >or=1 year of follow-up; and those who received only 1 dispensation of a statin during the first year after the index prescription. Follow-up continued until hospitalization for IHD or any other cardiovascular cause, death from any cause, emigration, or the end of the study period (June 30, 2007). The proportion of days covered (PDC) by therapy with statins was the exposure variable; it served as a proxy for adherence. PDC (and therefore adherence) was categorized as very low (or=75%) coverage. A proportional hazards model was fitted to estimate hazard ratio (HR) and 95% CIs for the association between time-dependent categories of PDC and time of IHD hospitalization, after correcting for covariates. RESULTS: A group of 90,832 patients was included; during follow-up, 1480 patients experienced a hospitalization for IHD. After the Cox proportional hazards model was adjusted for age, sex, type of statin dispensed at index prescription, current use of other selected drugs (ie, antidiabetics, antihypertensives, digitalis or organic nitrates, or other cardiac medications), Charlson comorbidity index, and whether or not a given patient switched statins, those with low, intermediate, or high statin coverage had HR (95% CI) values of 0.85 (0.72-0.98), 0.82 (0.71-0.95), and 0.81 (0.71-0.94), respectively, compared with patients with very low coverage. CONCLUSIONS: In these Italian subjects without a history of cardiovascular disease, low, intermediate, and high levels of adherence to statin pharmaco-therapy were associated with lower risk of nonfatal IHD compared with those who had very low (25 kg/m(2)) plasma sRAGE was significantly lower compared to lean subjects (1460+/-640 pg/mL vs 1710+/-693 pg/mL; P<0.05). In healthy subjects plasma levels of sRAGE were negatively correlated with BMI and waist/hip ratio supporting a possible protective role for these proteins before any evidence of diabetic or vascular complications. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. danilo.norata@unimi.it FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Grigore, Liliana AU - Grigore L FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Raselli, Sara AU - Raselli S FAU - Redaelli, Laura AU - Redaelli L FAU - Buccianti, Gherardo AU - Buccianti G FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080702 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Apolipoprotein A-I) RN - 0 (Blood Glucose) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Receptors, Immunologic) SB - IM MH - Aged MH - Apolipoprotein A-I/blood MH - Blood Glucose/analysis MH - *Body Mass Index MH - Cardiovascular Diseases/blood/*etiology/physiopathology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Overweight/*blood/complications/genetics/physiopathology MH - Polymorphism, Single Nucleotide MH - Receptor for Advanced Glycation End Products MH - Receptors, Immunologic/*blood/genetics MH - Regression Analysis MH - Risk Assessment MH - Risk Factors MH - *Waist-Hip Ratio EDAT- 2008/07/04 09:00 MHDA- 2009/05/01 09:00 CRDT- 2008/07/04 09:00 PHST- 2007/12/04 00:00 [received] PHST- 2008/02/28 00:00 [revised] PHST- 2008/03/11 00:00 [accepted] PHST- 2008/07/04 09:00 [pubmed] PHST- 2009/05/01 09:00 [medline] PHST- 2008/07/04 09:00 [entrez] AID - S0939-4753(08)00064-1 [pii] AID - 10.1016/j.numecd.2008.03.004 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2009 Feb;19(2):129-34. doi: 10.1016/j.numecd.2008.03.004. Epub 2008 Jul 2. PMID- 21291777 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121002 LR - 20110204 IS - 1933-2874 (Print) IS - 1876-4789 (Linking) VI - 2 IP - 6 DP - 2008 Dec TI - Ezetimibe/simvastatin compared with atorvastatin or rosuvastatin in lowering to specified levels both LDL-C and each of five other emerging risk factors for coronary heart disease: Non-HDL-cholesterol, TC/HDL-C, apolipoprotein B, apo-B/apo-A-I, or C-reactive protein. PG - 436-46 LID - 10.1016/j.jacl.2008.10.003 [doi] AB - BACKGROUND: Recent evidence suggests that in addition to low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), non-high-density lipoprotein cholesterol (non-HDL-C), some lipoprotein ratios, and C-reactive protein (CRP) are predictive of coronary heart disease (CHD) risk. This post-hoc analysis of two trials comparing single-tablet ezetimibe/simvastatin (EZE/SIMVA) to atorvastatin (ATORVA) or rosuvastatin (ROSUVA) evaluates the proportion of patients attaining LDL-C <70 mg/dL and specific levels of these emerging risk factors. METHODS: These were double-blind, 6-week, parallel group trials of hypercholesterolemic patients randomized to milligram equivalent doses of ATORVA versus EZE 10 mg/SIMVA, or to usual starting, next higher, and maximum doses of ROSUVA versus EZE/SIMVA. This analysis examined the percent of patients in prespecified dose comparisons and overall achievement of LDL-C <70 mg/dL and/or Apo-B <90 mg/dL, total cholesterol (TC)/HDL-C <4.0, or Apo-B/Apo-A-I <0.7 among all treated patients, non-HDL-C <100 mg/dL among patients with baseline triglycerides >/=200 mg/dL, or CRP <2.0 mg/L among patients with baseline CRP >/=2.0 mg/L. RESULTS: Within each trial, baseline characteristics were similar among groups. At all dose comparisons, significantly more patients receiving EZE/SIMVA reached LDL-C <70 mg/dL and achieved both LDL-C <70 mg/dL and either Apo-B <90 mg/dL, TC/HDL-C <4.0, or Apo-B/Apo-A-I <0.7 (EZE/SIMVA versus ATORVA) compared to ATORVA and ROSUVA. For most dose comparisons, significantly more patients receiving EZE/SIMVA attained both LDL-C <70 mg/dL and either non-HDL-C <100 mg/dL or CRP <2 mg/L compared to ATORVA or ROSUVA. CONCLUSION: The greater efficacy related to changes in blood lipids of EZE/SIMVA compared with both ATORVA and ROSUVA extends to changes in many emerging risk factors. Ultimate clinical implications of these findings still need to be defined. FAU - Davidson, Michael H AU - Davidson MH AD - University of Chicago, 515 N. State Street, Suite 2700, Chicago, IL USA. FAU - Abate, Nicola AU - Abate N FAU - Ballantyne, Christie M AU - Ballantyne CM FAU - Catapano, Alberico L AU - Catapano AL FAU - Xu, Xia AU - Xu X FAU - Lin, Jianxin AU - Lin J FAU - Rosenberg, Elizabeth AU - Rosenberg E FAU - Tershakovec, Andrew M AU - Tershakovec AM LA - eng PT - Journal Article DEP - 20081022 PL - United States TA - J Clin Lipidol JT - Journal of clinical lipidology JID - 101300157 EDAT- 2008/12/01 00:00 MHDA- 2008/12/01 00:01 CRDT- 2011/02/05 06:00 PHST- 2008/10/01 00:00 [received] PHST- 2008/10/19 00:00 [accepted] PHST- 2011/02/05 06:00 [entrez] PHST- 2008/12/01 00:00 [pubmed] PHST- 2008/12/01 00:01 [medline] AID - S1933-2874(08)00889-1 [pii] AID - 10.1016/j.jacl.2008.10.003 [doi] PST - ppublish SO - J Clin Lipidol. 2008 Dec;2(6):436-46. doi: 10.1016/j.jacl.2008.10.003. Epub 2008 Oct 22. PMID- 18684974 OWN - NLM STAT- MEDLINE DCOM- 20081006 LR - 20090127 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 181 IP - 4 DP - 2008 Aug 15 TI - The 15-lipoxygenase-modified high density lipoproteins 3 fail to inhibit the TNF-alpha-induced inflammatory response in human endothelial cells. PG - 2821-30 AB - Endothelial dysfunction represents one of the earliest events in vascular atherogenesis. Proinflammatory stimuli activate endothelial cells, resulting in an increased expression of adhesion molecules and chemoattractants that mediate leukocyte and monocyte adhesion, migration, and homing. High density lipoproteins (HDL) inhibit endothelial cell expression of adhesion molecules in response to proinflammatory stimuli. In the present work, we demonstrate that the modification of HDL(3) (the major and the most antiatherogenic HDL subfraction) by 15-lipoxygenase (15-LO), an enzyme overexpressed in the atherosclerotic lesions, impairs the anti-inflammatory activity of this lipoprotein. The 15-LO-modified HDL(3) failed to inhibit TNF-alpha-mediated mRNA and protein induction of adhesion molecules and MCP-1 in several models of human endothelial cells, and promoted inflammatory response by up-regulating the expression of such mediators of inflammation and by increasing monocyte adhesion to endothelial cells. Moreover, 15-LO-modified HDL(3) were unable to contrast the formation of reactive oxygen species in cells incubated with TNF-alpha, and increased the reactive oxygen species content in unstimulated cells. Activation of NF-kappaB and AP-1 was mainly involved in the expression of adhesion molecules and MCP-1 induced by 15-LO-HDL(3). Altogether, these results demonstrate that enzymatic modification induced by 15-LO impaired the protective role of HDL(3), generating a dysfunctional lipoprotein endowed with proinflammatory characteristics. FAU - Pirillo, Angela AU - Pirillo A AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. angela.pirillo@unimi.it FAU - Uboldi, Patrizia AU - Uboldi P FAU - Bolego, Chiara AU - Bolego C FAU - Kuhn, Hartmut AU - Kuhn H FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Cell Adhesion Molecules) RN - 0 (Inflammation Mediators) RN - 0 (Lipoproteins, HDL3) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.13.11.33 (ALOX15 protein, human) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) SB - AIM SB - IM EIN - J Immunol. 2008 Dec 15;181(12):8797 MH - Arachidonate 15-Lipoxygenase/biosynthesis/genetics/*physiology MH - Cell Adhesion Molecules/antagonists & inhibitors/biosynthesis MH - Cell Line MH - Cells, Cultured MH - Dose-Response Relationship, Immunologic MH - Endothelium, Vascular/enzymology/*immunology/*pathology MH - Humans MH - Inflammation Mediators/*antagonists & inhibitors/metabolism/*physiology MH - Lipoproteins, HDL3/*antagonists & inhibitors/*physiology MH - Microcirculation/immunology MH - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*physiology MH - U937 Cells EDAT- 2008/08/08 09:00 MHDA- 2008/10/07 09:00 CRDT- 2008/08/08 09:00 PHST- 2008/08/08 09:00 [pubmed] PHST- 2008/10/07 09:00 [medline] PHST- 2008/08/08 09:00 [entrez] AID - 181/4/2821 [pii] PST - ppublish SO - J Immunol. 2008 Aug 15;181(4):2821-30. PMID- 18218986 OWN - NLM STAT- MEDLINE DCOM- 20080506 LR - 20101118 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 28 IP - 5 DP - 2008 May TI - Long pentraxin 3, a key component of innate immunity, is modulated by high-density lipoproteins in endothelial cells. PG - 925-31 LID - 10.1161/ATVBAHA.107.160606 [doi] AB - OBJECTIVE: High-density lipoproteins (HDL) are endowed with cardiovascular protective activities. In addition to their role in reverse cholesterol transport, HDL exert several beneficial effects on endothelial cells, including the induction of endothelial nitric oxide synthase and prostacyclin release, and the control of the immune and inflammatory response. METHODS AND RESULTS: To identify possible mechanisms involved in these effects we investigated the modulation of the expression of acute phase proteins of the pentraxin superfamily, such as C-reactive protein (CRP), serum amyloid P component protein (SAP), and the long pentraxin 3 (PTX3) by HDL in human endothelial cells. HDL induced PTX3 mRNA expression and protein release, whereas no effect was observed on CRP and SAP expression. This effect was mainly dependent on the activation of the lysosphingolipids receptors-PI3K/Akt axis and was mimicked by sphingosine 1 phosphate and other S1P mimetics. This observation was confirmed in vivo; indeed an increased expression of PTX3 mRNA was detected in the aorta of transgenic mice overexpressing human apoA-I, compared to apoA-I knock-out mice. Furthermore, plasma levels of PTX3 significantly increased in C57BL/6 mice injected with HDL. CONCLUSIONS: These data suggest that part of the atheroprotective effects of HDL could result from the modulation of molecules that act as sensors of the immunoinflammatory balance in the vascular wall. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. Danilo.Norata@unimi.it FAU - Marchesi, Patrizia AU - Marchesi P FAU - Pirillo, Angela AU - Pirillo A FAU - Uboldi, Patrizia AU - Uboldi P FAU - Chiesa, Giulia AU - Chiesa G FAU - Maina, Virginia AU - Maina V FAU - Garlanda, Cecilia AU - Garlanda C FAU - Mantovani, Alberto AU - Mantovani A FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080124 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Acute-Phase Proteins) RN - 0 (Apolipoprotein A-I) RN - 0 (Cholesterol, HDL) RN - 0 (Lipoproteins, HDL) RN - 0 (RNA, Messenger) RN - 0 (Serum Amyloid P-Component) RN - 148591-49-5 (PTX3 protein) RN - 9007-41-4 (C-Reactive Protein) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM CIN - Arterioscler Thromb Vasc Biol. 2008 May;28(5):809-11. PMID: 18421007 MH - Acute-Phase Proteins/metabolism MH - Animals MH - Aorta/drug effects/metabolism/pathology MH - Apolipoprotein A-I/genetics/metabolism MH - C-Reactive Protein/*metabolism MH - Cholesterol, HDL/pharmacology MH - Endothelial Cells/*metabolism/pathology MH - Female MH - Humans MH - Immunity, Innate/*physiology MH - Lipoproteins, HDL/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/metabolism MH - Serum Amyloid P-Component/*metabolism MH - Signal Transduction/drug effects EDAT- 2008/01/26 09:00 MHDA- 2008/05/07 09:00 CRDT- 2008/01/26 09:00 PHST- 2008/01/26 09:00 [pubmed] PHST- 2008/05/07 09:00 [medline] PHST- 2008/01/26 09:00 [entrez] AID - ATVBAHA.107.160606 [pii] AID - 10.1161/ATVBAHA.107.160606 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2008 May;28(5):925-31. doi: 10.1161/ATVBAHA.107.160606. Epub 2008 Jan 24. PMID- 21291725 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121002 LR - 20110204 IS - 1933-2874 (Print) IS - 1876-4789 (Linking) VI - 2 IP - 2 DP - 2008 Apr TI - Effect of ezetimibe/simvastatin versus atorvastatin or rosuvastatin on modifying lipid profiles in patients with diabetes, metabolic syndrome, or neither: Results of two subgroup analyses. PG - 91-105 LID - 10.1016/j.jacl.2008.02.002 [doi] AB - BACKGROUND: Patients with diabetes mellitus (DM) and metabolic syndrome (MS) are at increased risk of developing coronary heart disease. OBJECTIVE: To compare the effects of ezetimibe/simvastatin (E/S) combination therapy, atorvastatin, and rosuvastatin in patients with DM, MS without DM, or neither disease. METHODS: Subgroup analysis of data from two 6-week, randomized, double-blind trials comparing E/S 10/10, 10/20, 10/40, or 10/80 mg with either atorvastatin 10, 20, 40, or 80 mg (Study 1), or rosuvastatin 10, 20, or 40 mg (Study 2). Treatments were compared by pooling across all doses for effects on low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), non-HDL-C, apolipoprotein B (ApoB), LDL-C:HDL-C, TC:HDL-C, and LDL-C goal attainment. RESULTS: E/S provided greater improvements than atorvastatin or rosuvastatin in LDL-C, TC, HDL-C (vs atorvastatin only), non-HDL-C, LDL-C:HDL-C, TC:HDL-C, and ApoB in all disease subgroups. There were no interactions of treatment by disease subgroup for these parameters, indicating a consistent treatment difference favoring E/S effect across the disease subgroups. A greater percentage of patients receiving E/S than atorvastatin or rosuvastatin attained their individual National Cholesterol Education Program Adult Treatment Panel III LDL-C goals, LDL-C <100 mg/dL, LDL-C <70 mg/dL, and non-HDL-C goals regardless of subgroup. All treatments were well-tolerated, with generally similar adverse experience rates. CONCLUSIONS: Overall, E/S generally provided greater efficacy than either atorvastatin or rosuvastatin that was consistent across the subgroups of patients with DM, MS, or neither, in agreement with the results from the full study cohorts. FAU - Abate, Nicola AU - Abate N AD - University of Texas Southwestern Medical Center, Dallas, TX. FAU - Catapano, Alberico L AU - Catapano AL FAU - Ballantyne, Christie M AU - Ballantyne CM FAU - Davidson, Michael H AU - Davidson MH FAU - Polis, Adam AU - Polis A FAU - Smugar, Steven S AU - Smugar SS FAU - Tershakovec, Andrew M AU - Tershakovec AM LA - eng PT - Journal Article DEP - 20080215 PL - United States TA - J Clin Lipidol JT - Journal of clinical lipidology JID - 101300157 EDAT- 2008/04/01 00:00 MHDA- 2008/04/01 00:01 CRDT- 2011/02/05 06:00 PHST- 2008/01/30 00:00 [received] PHST- 2008/02/12 00:00 [accepted] PHST- 2011/02/05 06:00 [entrez] PHST- 2008/04/01 00:00 [pubmed] PHST- 2008/04/01 00:01 [medline] AID - S1933-2874(08)00069-X [pii] AID - 10.1016/j.jacl.2008.02.002 [doi] PST - ppublish SO - J Clin Lipidol. 2008 Apr;2(2):91-105. doi: 10.1016/j.jacl.2008.02.002. Epub 2008 Feb 15. PMID- 18561502 OWN - NLM STAT- MEDLINE DCOM- 20080710 LR - 20181113 IS - 1176-6344 (Print) IS - 1176-6344 (Linking) VI - 4 IP - 2 DP - 2008 TI - Combination therapy in cholesterol reduction: focus on ezetimibe and statins. PG - 267-78 AB - Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Many patients do not achieve LDL-C goal on the initial dose of statin and the majority of these patients does not reach their goal after 6 months. As a consequence, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic hypocholesterolemic strategy is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively and safely co-administered with any dose of any statin and, compared with the single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through dual inhibition of both cholesterol production and absorption. We summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using ezetimibe either alone or co-administered with statins in controlling elevated levels of plasma LDL cholesterol. FAU - Grigore, Liliana AU - Grigore L AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - New Zealand TA - Vasc Health Risk Manag JT - Vascular health and risk management JID - 101273479 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Anticholesteremic Agents/pharmacology/*therapeutic use MH - Azetidines/pharmacology/*therapeutic use MH - Cardiovascular Diseases/blood/etiology/*prevention & control MH - Cholesterol/blood/*metabolism MH - Cholesterol, LDL/blood MH - Dose-Response Relationship, Drug MH - Drug Therapy, Combination MH - Ezetimibe MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/*therapeutic use MH - Hypercholesterolemia/blood/complications/*drug therapy MH - Intestinal Absorption/drug effects MH - Liver/drug effects/metabolism MH - Practice Guidelines as Topic MH - Treatment Outcome RF - 57 PMC - PMC2496970 EDAT- 2008/06/20 09:00 MHDA- 2008/07/11 09:00 CRDT- 2008/06/20 09:00 PHST- 2008/06/20 09:00 [pubmed] PHST- 2008/07/11 09:00 [medline] PHST- 2008/06/20 09:00 [entrez] PST - ppublish SO - Vasc Health Risk Manag. 2008;4(2):267-78. PMID- 18001316 OWN - NLM STAT- MEDLINE DCOM- 20080306 LR - 20151119 IS - 0767-3981 (Print) IS - 0767-3981 (Linking) VI - 21 Suppl 2 DP - 2007 Nov TI - The pharmacologic elegance of inhibiting cholesterol absorption and synthesis while providing a homeostatic balance. PG - 21-6 AB - The recent discoveries on the concerted role of several mechanisms involved in regulating the balance of body cholesterol highlight the role of intestinal absorption. Selective modulators of intestinal cholesterol absorption are available that offer a new pharmacologic approach to the modulation of total body cholesterol homeostasis and to a more effective reduction of low-density-lipoprotein cholesterol. FAU - Catapano, Alberico L AU - Catapano AL AD - Center for the Study of Atherosclerosis and Laboratory of Lipoprotein Metabolism, Department of Pharmacological Sciences, University of Milan, Milan, Italy. alberico.catapano@unimi.it LA - eng PT - Journal Article PT - Review PL - England TA - Fundam Clin Pharmacol JT - Fundamental & clinical pharmacology JID - 8710411 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Animals MH - Anticholesteremic Agents/*pharmacology/therapeutic use MH - Azetidines/pharmacology/therapeutic use MH - Cholesterol/biosynthesis/*metabolism/pharmacokinetics MH - Ezetimibe MH - Homeostasis/*drug effects MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use MH - Hypercholesterolemia/drug therapy/metabolism MH - Intestinal Absorption/drug effects MH - Liver/drug effects/metabolism RF - 33 EDAT- 2007/11/16 09:00 MHDA- 2008/03/07 09:00 CRDT- 2007/11/16 09:00 PHST- 2007/11/16 09:00 [pubmed] PHST- 2008/03/07 09:00 [medline] PHST- 2007/11/16 09:00 [entrez] AID - FCP534 [pii] AID - 10.1111/j.1472-8206.2007.00534.x [doi] PST - ppublish SO - Fundam Clin Pharmacol. 2007 Nov;21 Suppl 2:21-6. doi: 10.1111/j.1472-8206.2007.00534.x. PMID- 17595187 OWN - NLM STAT- MEDLINE DCOM- 20080310 LR - 20161124 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 22 IP - 11 DP - 2007 Nov TI - Improvement of endothelial function in uraemic patients on peritoneal dialysis: a possible role for 5-MTHF administration. PG - 3292-7 AB - BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. METHODS: We examined the effect of oral treatment with 15 mg/daily of 5-methyltetrahydrofolate (5-MTHF) for 12 weeks, on homocysteinaemia and endothelial function in 19 patients undergoing peritoneal dialysis and compared them, for the same period of time, to a control group of patients on peritoneal dialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by the inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after sublingual administration of glyceryl trinitrate. Finally, oxidative stress was assessed by evaluating the conjugated dienes plasma levels. RESULTS: Plasma homocysteine concentrations fell by 30% after oral treatment with 5-MTHF. Endothelial function improved significantly after oral 5-MTHF treatment (13.8 +/- 1.2% vs 11.4 +/- 1.4%; P < 0.02) while in the control group we observed a worsening of basal values from 12.1 +/- 2.66% to 8.7 +/- 2.90% (P < 0.02). The conjugated dienes plasma levels did not change either. CONCLUSIONS: Our study demonstrated that 5-MTHF administration improves endothelial dysfunction in patients undergoing peritoneal dialysis. This effect appears to be independent of the reduction in homocysteine plasma levels. FAU - Baragetti, Ivano AU - Baragetti I AD - Department of Internal Medicine, Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy. i.baragetti@bassini.hsgerardo.org FAU - Raselli, Sara AU - Raselli S FAU - Stucchi, Andrea AU - Stucchi A FAU - Terraneo, Veronica AU - Terraneo V FAU - Furiani, Silvia AU - Furiani S FAU - Buzzi, Laura AU - Buzzi L FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Alberghini, Elena AU - Alberghini E FAU - Catapano, Alberico L AU - Catapano AL FAU - Buccianti, Gherardo AU - Buccianti G LA - eng PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070625 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Tetrahydrofolates) RN - 0LVT1QZ0BA (Homocysteine) RN - 935E97BOY8 (Folic Acid) RN - TYK22LML8F (5-methyltetrahydrofolate) SB - IM CIN - Nephrol Dial Transplant. 2008 Mar;23(3):1069; author reply 1069-71. PMID: 17951310 MH - Aged MH - Diabetic Nephropathies/drug therapy/*therapy MH - Endothelium, Vascular/diagnostic imaging/drug effects/*physiopathology MH - Female MH - Folic Acid/blood MH - Homocysteine/*blood MH - Humans MH - Kidney Failure, Chronic/drug therapy/*therapy MH - Male MH - Middle Aged MH - *Peritoneal Dialysis MH - Tetrahydrofolates/*therapeutic use MH - Ultrasonography MH - Uremia/drug therapy/*therapy MH - Vasodilation/drug effects EDAT- 2007/06/28 09:00 MHDA- 2008/03/11 09:00 CRDT- 2007/06/28 09:00 PHST- 2007/06/28 09:00 [pubmed] PHST- 2008/03/11 09:00 [medline] PHST- 2007/06/28 09:00 [entrez] AID - gfm402 [pii] AID - 10.1093/ndt/gfm402 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2007 Nov;22(11):3292-7. doi: 10.1093/ndt/gfm402. Epub 2007 Jun 25. PMID- 17823381 OWN - NLM STAT- MEDLINE DCOM- 20071018 LR - 20161122 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 38 IP - 10 DP - 2007 Oct TI - Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery. PG - 2844-6 AB - BACKGROUND AND PURPOSE: The evaluation of the leptin:adiponectin ratio (L:A) has been suggested as an atherosclerotic index in patients with type 2 diabetes and a useful parameter to assess insulin resistance in patients with and without diabetes. METHODS: We investigated, therefore, the relationship between L:A ratio and intima media thickness (IMT), an independent predictor of cardiovascular disease, in 110 healthy males. RESULTS: L:A ratio was significantly correlated to body mass index, waist, hip, waist-to-hip ratio, systolic blood pressure, IMT, high-density lipoprotein, apolipoprotein A-I, glucose, and the homeostasis model of insulin resistance-revised. No significant correlation was observed with age, diastolic blood pressure, low-density lipoprotein, triglycerides, apolipoprotein B, ApoB/ApoA-I ratio, insulin, alanine transaminase, gamma-glutamyl-transferase, and resistin. In addition, when the relationship between IMT and adiponectin or leptin alone was analyzed, only leptin plasma levels significantly associated with IMT (r=0.301, P<0.01). In a multiple regression analysis including in the statistical model the risk factors known to affect IMT (age, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, total cholesterol, body mass index, glucose, and L:A ratio), we observed that only age, L:A, and glucose were independent predictors of IMT. As expected, obese subjects (body mass index >30 kg/m(2)) showed a significantly higher L:A ratio compared with nonobese subjects (1.20 versus 0.42, respectively, P<0.001); in addition, subjects with the metabolic syndrome showed a significantly higher L:A ratio level (0.79) compared with subjects without (0.52) (P<0.01). CONCLUSIONS: We show here that the L:A ratio is a powerful independent predictor of IMT in healthy subjects and correlates with several anthropometric, metabolic, and clinical parameters better than each single adipokine. FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Raselli, Sara AU - Raselli S FAU - Grigore, Liliana AU - Grigore L FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Dozio, Elena AU - Dozio E FAU - Magni, Paolo AU - Magni P FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070906 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (Adiponectin) RN - 0 (Biomarkers) RN - 0 (Leptin) SB - IM CIN - Stroke. 2008 Feb;39(2):e32-3; author reply e34. PMID: 18096836 MH - Adiponectin/*blood MH - Adult MH - Aged MH - Biomarkers/blood MH - Carotid Artery, Common/*pathology MH - Carotid Stenosis/*blood/*pathology MH - Humans MH - Leptin/*blood MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Regression Analysis MH - Tunica Media/pathology EDAT- 2007/09/08 09:00 MHDA- 2007/10/19 09:00 CRDT- 2007/09/08 09:00 PHST- 2007/09/08 09:00 [pubmed] PHST- 2007/10/19 09:00 [medline] PHST- 2007/09/08 09:00 [entrez] AID - STROKEAHA.107.485540 [pii] AID - 10.1161/STROKEAHA.107.485540 [doi] PST - ppublish SO - Stroke. 2007 Oct;38(10):2844-6. doi: 10.1161/STROKEAHA.107.485540. Epub 2007 Sep 6. PMID- 17662693 OWN - NLM STAT- MEDLINE DCOM- 20070928 LR - 20131121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 361 IP - 2 DP - 2007 Sep 21 TI - ApoE gene delivery inhibits severe hypercholesterolemia in newborn ApoE-KO mice. PG - 543-8 AB - Apolipoprotein E, a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. Inherited deficiency of this protein results in type III hyperlipoproteinemia in humans. ApoE-knockout mice, which develop spontaneous hypercholesterolemia, are an excellent model of human atherosclerosis. Here we investigated the therapeutic effects of a plasmid vector encoding human APOE3 sequence intramuscularly injected in hypercholesterolemic newborn mice at the ages of 5 and 14 days. We further explored the possibility of inducing tolerance in newborns when injected early. Our data show that direct i.m. naked DNA injection reduces severe hypercholesterolemia in newborn mice. Moreover, when naked DNA is administrated early, no immune response is generated against the human APOE, allowing repeated administrations. Neonatal therapies are important for the treatment of many genetic childhood diseases where early administration is required to prevent developmental damage. We propose the use of direct i.m. naked gene transfer in newborns to prevent long-term damages arising from hypercholesterolemic conditions. FAU - Signori, Emanuela AU - Signori E AD - Institute of Neurobiology and Molecular Medicine, CNR-ARTOV, 00133 Rome, Italy. emanuela.signori@artov.inmm.cnr.it FAU - Rinaldi, Monica AU - Rinaldi M FAU - Fioretti, Daniela AU - Fioretti D FAU - Iurescia, Sandra AU - Iurescia S FAU - Seripa, Davide AU - Seripa D FAU - Perrone, Giuseppe AU - Perrone G FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Fazio, Vito Michele AU - Fazio VM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070723 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antibodies) RN - 0 (Apolipoproteins E) RN - 0 (DNA, Complementary) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Animals, Newborn MH - Antibodies MH - Apolipoproteins E/administration & dosage/*deficiency/*genetics MH - Atherosclerosis/pathology MH - Cholesterol/blood MH - DNA, Complementary/administration & dosage MH - Female MH - *Genetic Therapy MH - Genetic Vectors MH - Hypercholesterolemia/*genetics/*prevention & control MH - Immunity MH - Injections, Intramuscular MH - Male MH - Mice MH - Mice, Knockout MH - Plasmids/metabolism MH - Time Factors MH - *Transfection EDAT- 2007/07/31 09:00 MHDA- 2007/09/29 09:00 CRDT- 2007/07/31 09:00 PHST- 2007/07/04 00:00 [received] PHST- 2007/07/10 00:00 [accepted] PHST- 2007/07/31 09:00 [pubmed] PHST- 2007/09/29 09:00 [medline] PHST- 2007/07/31 09:00 [entrez] AID - S0006-291X(07)01500-8 [pii] AID - 10.1016/j.bbrc.2007.07.046 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2007 Sep 21;361(2):543-8. doi: 10.1016/j.bbrc.2007.07.046. Epub 2007 Jul 23. PMID- 17055512 OWN - NLM STAT- MEDLINE DCOM- 20071016 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 193 IP - 2 DP - 2007 Aug TI - Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: molecular mechanisms and gene expression studies. PG - 321-7 AB - OBJECTIVE: Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study, we investigated the effects of post-prandial TGRLs from type IV hyperlipidemic subjects on endothelial activation addressing the effects of the lipoproteins on intracellular pathways and gene expression. METHODS: Thirty fasted hypertriglyceridemic patients were given an oral fat load (OFL) and blood samples were collected before the OFL (T0) and 2, 4, 6 and 8h thereafter. Endothelial function, determined as flow-mediated dilatation of the brachial artery, was assessed at the same time points. TGRLs were isolated at T0 and T4 (PP-TGRL) for in vitro studies. RESULTS: Compared with TGRLs, PP-TGRLs induced to a larger extent phosphorylation of p38 MAPK, CREB and IKB-alpha in human endothelial cells and increased the DNA binding activity of CREB, NFAT and NF-kappaB. Furthermore, PP-TRGLs upregulated the expression of several pro-inflammatory genes including vascular cell adhesion molecule-1 (VCAM-1), PECAM-1, ELAM-1, intercellular adhesion molecule-1 (ICAM-1), P-selectin, MCP-1, interleukin-6 (IL-6), TLR-4, CD40, ADAMTS1 and PAI-1. CONCLUSION: These effects may relate to the severe impairment of endothelial function seen during the post-prandial phase in hypertriglyceridemic patients. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan,Via Balzaretti 9, 20133 Milan, Italy. Danilo.Norata@unimi.it FAU - Grigore, Liliana AU - Grigore L FAU - Raselli, Sara AU - Raselli S FAU - Redaelli, Laura AU - Redaelli L FAU - Hamsten, Anders AU - Hamsten A FAU - Maggi, Franco AU - Maggi F FAU - Eriksson, Per AU - Eriksson P FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061020 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Dietary Fats) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adult MH - Cholesterol/metabolism MH - Dietary Fats/*pharmacology MH - Endothelial Cells/*drug effects MH - Gene Expression MH - Humans MH - Hyperlipoproteinemia Type IV/genetics/*physiopathology MH - Lipid Metabolism/drug effects/*genetics MH - Male MH - Middle Aged MH - Postprandial Period MH - Signal Transduction MH - Triglycerides/metabolism MH - Vascular Diseases/*genetics/*physiopathology EDAT- 2006/10/24 09:00 MHDA- 2007/10/17 09:00 CRDT- 2006/10/24 09:00 PHST- 2006/06/30 00:00 [received] PHST- 2006/09/15 00:00 [revised] PHST- 2006/09/18 00:00 [accepted] PHST- 2006/10/24 09:00 [pubmed] PHST- 2007/10/17 09:00 [medline] PHST- 2006/10/24 09:00 [entrez] AID - S0021-9150(06)00560-0 [pii] AID - 10.1016/j.atherosclerosis.2006.09.015 [doi] PST - ppublish SO - Atherosclerosis. 2007 Aug;193(2):321-7. doi: 10.1016/j.atherosclerosis.2006.09.015. Epub 2006 Oct 20. PMID- 17524375 OWN - NLM STAT- MEDLINE DCOM- 20071024 LR - 20171213 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 75 IP - 3 DP - 2007 Aug 1 TI - Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux. PG - 566-74 AB - OBJECTIVE: Elevated levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease. The anti-atherosclerotic function of HDL is mainly ascribed to its role in reverse cholesterol transport, and requires the integrity of HDL structure. Experimental evidence suggests that the ability of HDL to promote removal of excess cholesterol from peripheral cells is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its protective function, suggesting that not all forms of modified lipoprotein may be atherogenic. In the present study we investigated the effect of a mild oxidation of HDL(3) on its function as cholesterol acceptor. METHODS AND RESULTS: A mild oxidative stress (induced by 15 min exposure of HDL(3) to 1 microM Cu(++) or to 15-lipoxygenase) caused the formation of pre-beta-migrating particles. Compared to native lipoprotein, mildly modified HDL(3) induced a significant ATP-binding cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1-mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts. CONCLUSIONS: A mild oxidative modification of HDL(3) may improve its function as cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a process that may reduce foam cell formation. FAU - Pirillo, Angela AU - Pirillo A AD - Department of Pharmacological Sciences, Via Balzaretti, 9, 20133 Milano, Italy. angela.pirillo@unimi.it FAU - Uboldi, Patrizia AU - Uboldi P FAU - Pappalardo, Gianluca AU - Pappalardo G FAU - Kuhn, Hartmut AU - Kuhn H FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070504 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (ABCA1 protein, human) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipoproteins, HDL3) RN - 0 (Phospholipids) RN - 789U1901C5 (Copper) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) RN - SX6K58TVWC (Glyburide) SB - IM MH - ATP Binding Cassette Transporter 1 MH - ATP-Binding Cassette Transporters/*metabolism MH - Arachidonate 15-Lipoxygenase/pharmacology MH - Biological Transport/drug effects MH - Cell Line MH - Cholesterol/*metabolism MH - Copper/pharmacology MH - Fibroblasts/metabolism MH - Glyburide/pharmacology MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Lipid Metabolism/drug effects MH - Lipoproteins, HDL3/*metabolism MH - Macrophages/drug effects/*metabolism MH - Oxidative Stress/physiology MH - Phospholipids/metabolism MH - Protein Binding EDAT- 2007/05/26 09:00 MHDA- 2007/10/25 09:00 CRDT- 2007/05/26 09:00 PHST- 2006/09/14 00:00 [received] PHST- 2007/04/06 00:00 [revised] PHST- 2007/04/18 00:00 [accepted] PHST- 2007/05/26 09:00 [pubmed] PHST- 2007/10/25 09:00 [medline] PHST- 2007/05/26 09:00 [entrez] AID - S0008-6363(07)00198-8 [pii] AID - 10.1016/j.cardiores.2007.04.021 [doi] PST - ppublish SO - Cardiovasc Res. 2007 Aug 1;75(3):566-74. doi: 10.1016/j.cardiores.2007.04.021. Epub 2007 May 4. PMID- 17659159 OWN - NLM STAT- MEDLINE DCOM- 20071017 LR - 20181201 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 23 IP - 8 DP - 2007 Aug TI - Meta-analysis of the cholesterol-lowering effect of ezetimibe added to ongoing statin therapy. PG - 2009-26 AB - OBJECTIVE: To review and analyse the evidence for the cholesterol-lowering effect of ezetimibe in adult patients with hypercholesterolaemia who are not at low-density lipoprotein cholesterol (LDL-C) goal on statin monotherapy. RESEARCH DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE and EMBASE were searched to identify ezetimibe randomised controlled trials (RCTs) published between January 1993 and December 2005. The meta-analysis combined data from RCTs, with a minimum treatment duration of 6 weeks, that compared treatment with ezetimibe 10 mg/day or placebo added to current statin therapy. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C), and number of patients achieving LDL-C treatment goal. Meta-analysis results are presented for a modified version of the inverse variance random effects model. RESULTS: Five RCTs involving a total of 5039 patients were included in the meta-analysis. The weighted mean difference (WMD) between treatments significantly favoured the ezetimibe/statin combination over placebo/statin for TC (-16.1% (-17.3, -14.8); p < 0.0001), LDL-C (-23.6% (-25.6, -21.7); p < 0.0001) and HDL-C (1.7% (0.9, 2.5); p < 0.0001). The relative risk of reaching the LDL-C treatment goal was significantly higher for patients on ezetimibe/statin relative to those on placebo/statin (3.4 (2.0, 5.6); p < 0.0001). In pre-defined sub-group analyses of studies in patients with coronary heart disease, the WMD between treatments remained significantly in favour of ezetimibe/statin (p < 0.0001) for TC and LDL-C but was no longer significant for HDL-C. Elevations in creatine kinase, alanine aminotransferase or aspartate aminotransferase that were considered as an adverse effect did not differ significantly between treatments. CONCLUSIONS: The meta-analysis we performed included only five studies and was restricted to analysis of the changes in cholesterol levels relative to baseline. However, the results suggest that ezetimibe co-administered with ongoing statin therapy provides significant additional lipid-lowering in patients not at LDL-C goal on statin therapy alone, allowing more patients to reach their LDL-C goal. FAU - Mikhailidis, D P AU - Mikhailidis DP AD - Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free Hospital, Royal Free and University College School of Medicine, London, UK. MIKHAILIDIS@aol.com FAU - Sibbring, G C AU - Sibbring GC FAU - Ballantyne, C M AU - Ballantyne CM FAU - Davies, G M AU - Davies GM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipoproteins) RN - 0 (Placebos) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Anticholesteremic Agents/administration & dosage/*therapeutic use MH - Azetidines/administration & dosage/*therapeutic use MH - Cholesterol/blood MH - Ezetimibe MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*therapeutic use MH - Hypercholesterolemia/*drug therapy MH - Lipoproteins/blood MH - Placebos MH - Randomized Controlled Trials as Topic MH - Triglycerides/blood EDAT- 2007/07/31 09:00 MHDA- 2007/10/18 09:00 CRDT- 2007/07/31 09:00 PHST- 2007/07/31 09:00 [pubmed] PHST- 2007/10/18 09:00 [medline] PHST- 2007/07/31 09:00 [entrez] AID - 10.1185/030079907X210507 [doi] PST - ppublish SO - Curr Med Res Opin. 2007 Aug;23(8):2009-26. doi: 10.1185/030079907X210507 . PMID- 17611624 OWN - NLM STAT- MEDLINE DCOM- 20100423 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 2 IP - 7 DP - 2007 Jul 4 TI - ASSET (Age/Sex Standardised Estimates of Treatment): a research model to improve the governance of prescribing funds in Italy. PG - e592 AB - BACKGROUND: The primary objective of this study was to make the first step in the modelling of pharmaceutical demand in Italy, by deriving a weighted capitation model to account for demographic differences among general practices. The experimental model was called ASSET (Age/Sex Standardised Estimates of Treatment). METHODS AND MAJOR FINDINGS: Individual prescription costs and demographic data referred to 3,175,691 Italian subjects and were collected directly from three Regional Health Authorities over the 12-month period between October 2004 and September 2005. The mean annual prescription cost per individual was similar for males (196.13 euro) and females (195.12 euro). After 65 years of age, the mean prescribing costs for males were significantly higher than females. On average, costs for a 75-year-old subject would be 12 times the costs for a 25-34 year-old subject if male, 8 times if female. Subjects over 65 years of age (22% of total population) accounted for 56% of total prescribing costs. The weightings explained approximately 90% of the evolution of total prescribing costs, in spite of the pricing and reimbursement turbulences affecting Italy in the 2000-2005 period. The ASSET weightings were able to explain only about 25% of the variation in prescribing costs among individuals. CONCLUSIONS: If mainly idiosyncratic prescribing by general practitioners causes the unexplained variations, the introduction of capitation-based budgets would gradually move practices with high prescribing costs towards the national average. It is also possible, though, that the unexplained individual variation in prescribing costs is the result of differences in the clinical characteristics or socio-economic conditions of practice populations. If this is the case, capitation-based budgets may lead to unfair distribution of resources. The ASSET age/sex weightings should be used as a guide, not as the ultimate determinant, for an equitable allocation of prescribing resources to regional authorities and general practices. FAU - Favato, Giampiero AU - Favato G AD - School of Projects, Processes and Systems, Henley Management College, Henley-on-Thames, United Kindgom. gfavato@chicagogsb.edu FAU - Mariani, Paolo AU - Mariani P FAU - Mills, Roger W AU - Mills RW FAU - Capone, Alessandro AU - Capone A FAU - Pelagatti, Matteo AU - Pelagatti M FAU - Pieri, Vasco AU - Pieri V FAU - Marcobelli, Alberico AU - Marcobelli A FAU - Trotta, Maria G AU - Trotta MG FAU - Zucchi, Alberto AU - Zucchi A FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article DEP - 20070704 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Aging/physiology MH - Child MH - Child, Preschool MH - Cost of Illness MH - Delivery of Health Care/*economics/legislation & jurisprudence MH - Demography MH - Drug Prescriptions/*economics MH - Female MH - Humans MH - Italy MH - Legislation, Medical MH - Male MH - Middle Aged MH - *Research Design MH - Sex Characteristics PMC - PMC1899227 GN - NLM: Original DateCompleted: 20070806 EDAT- 2007/07/06 09:00 MHDA- 2007/07/06 09:01 CRDT- 2007/07/06 09:00 PHST- 2007/03/12 00:00 [received] PHST- 2007/05/29 00:00 [accepted] PHST- 2007/07/06 09:00 [pubmed] PHST- 2007/07/06 09:01 [medline] PHST- 2007/07/06 09:00 [entrez] AID - 10.1371/journal.pone.0000592 [doi] PST - epublish SO - PLoS One. 2007 Jul 4;2(7):e592. doi: 10.1371/journal.pone.0000592. PMID- 17598818 OWN - NLM STAT- MEDLINE DCOM- 20070816 LR - 20171116 IS - 0954-6820 (Print) IS - 0954-6820 (Linking) VI - 262 IP - 1 DP - 2007 Jul TI - Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction. PG - 104-12 AB - OBJECTIVE: Resistin is an adipokine that has been suggested to be correlated with markers of inflammation and to be predictive of coronary atherosclerosis and type II diabetes in humans. A common single nucleotide polymorphism (SNP) (-420C/G) in the promoter of resistin is associated with increased resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of the -420C/G polymorphism with metabolic syndrome, obesity, myocardial infarction and kidney disease. DESIGN AND RESULTS: First we studied 1542 subjects from the PLIC study (a population based cohort). GG carriers showed an higher prevalence of obesity and metabolic syndrome as well as increased plasma triglycerides levels, BMI, systolic and diastolic blood pressure and cardiovascular risk according to Framingham algorithm (P < 0.05 for all). Next we investigated the presence of the -420C/G resistin polymorphism in a case-control study that included 300 subject with myocardial infarction and 300 age and sex matched controls and then we studied the role of the -420C/G SNP in 88 patients with mild to moderate renal dysfunction. No statistically significant differences in allele frequencies between the PLIC study, the myocardial infarction (MI) cases and the subjects with renal dysfunction were observed. Pro-inflammatory gene expression profiling of peripheral blood mononuclear cells failed to detect any difference between wild type subjects and carriers of the rare allele. CONCLUSION: Our data suggest that the presence of the -420C/G SNP of the resistin gene is associated with increased obesity and metabolic syndrome, although it is not different in subjects at high cardiovascular risk such as patients with myocardial infarction or patients with renal dysfunction compared with controls. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. Danilo.Norata@unimi.it FAU - Ongari, M AU - Ongari M FAU - Garlaschelli, K AU - Garlaschelli K FAU - Tibolla, G AU - Tibolla G FAU - Grigore, L AU - Grigore L FAU - Raselli, S AU - Raselli S FAU - Vettoretti, S AU - Vettoretti S FAU - Baragetti, I AU - Baragetti I FAU - Noto, D AU - Noto D FAU - Cefalu, A B AU - Cefalu AB FAU - Buccianti, G AU - Buccianti G FAU - Averna, M AU - Averna M FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 RN - 0 (Lipids) RN - 0 (RNA, Messenger) RN - 0 (Resistin) SB - IM MH - Adult MH - Aged MH - Chronic Disease MH - Cohort Studies MH - Female MH - Gene Expression MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Kidney Diseases/blood/*genetics MH - Lipids/blood MH - Male MH - Metabolic Syndrome/blood/*genetics MH - Middle Aged MH - Myocardial Infarction/blood/*genetics MH - Obesity/blood/*genetics MH - Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic/*genetics MH - RNA, Messenger/genetics MH - Resistin/biosynthesis/*genetics EDAT- 2007/06/30 09:00 MHDA- 2007/08/19 09:00 CRDT- 2007/06/30 09:00 PHST- 2007/06/30 09:00 [pubmed] PHST- 2007/08/19 09:00 [medline] PHST- 2007/06/30 09:00 [entrez] AID - JIM1787 [pii] AID - 10.1111/j.1365-2796.2007.01787.x [doi] PST - ppublish SO - J Intern Med. 2007 Jul;262(1):104-12. doi: 10.1111/j.1365-2796.2007.01787.x. PMID- 17300133 OWN - NLM STAT- MEDLINE DCOM- 20070809 LR - 20070611 IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 16 IP - 6 DP - 2007 Jun TI - Monitoring statin safety in primary care. PG - 652-7 AB - PURPOSE: To verify General Practitioners (GPs) compliance to the recommended laboratory monitoring for statin users. METHODS: A retrospective study was conducted collecting data from the database of Italian College of General Practitioners, named Health Search; all the participant physicians used an automatic pop-up which reminds them to periodically check liver enzyme levels in statin-users. We examined the patients who received their first statin prescription from 29 November 1999 to 28 November, 2002. CPK, ASL, AST, and creatinine values recorded before and after the first prescription were evaluated. The minimum and maximum observation time before and after prescription were 6 and 42 months, respectively. The prevalence of laboratory monitoring prescribed by GPs was calculated at baseline and during follow-up for all patients and for the subgroup of high-risk patients. RESULTS: We identified 14 120 first-ever statin users (male 47.4%). CPK, AST, ALT and creatinine tests were prescribed at least once at baseline in 8.5%, 53.9%, 50.9%, and 64.0% of patients, respectively; during the follow-up 37.8%, 64.4%, 60.3%, and 61.5% of patient received the same tests prescriptions, respectively. No difference between high-risk and non-high-risk patients was observed. During the follow-up enzyme levels greater than three times the upper normal limit were recorded in 0.4%, 0.1%, 0.1%, and 0.3% of subjects for CPK, AST, ALT and creatinine, respectively. CONCLUSION: Adherence to the recommended laboratory monitoring for statin users is very low among Italian GPs, even for high-risk patients. Automatic reminders which pop-up whenever statins are prescribed are ineffective. CI - Copyright (c) 2007 John Wiley & Sons, Ltd. FAU - Tragni, Elena AU - Tragni E AD - Epidemiology and Preventive Pharmacology Center, Department of Pharmacological Sciences, University of Milan, Via Balzaretti, Milan, Italy. elena.tragni@unimi.it FAU - Filippi, Alessandro AU - Filippi A FAU - Mazzaglia, Giampiero AU - Mazzaglia G FAU - Sessa, Emiliano AU - Sessa E FAU - Cricelli, Claudio AU - Cricelli C FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipids) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 2.7.3.2 (Creatine Kinase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Alanine Transaminase/blood MH - Aspartate Aminotransferases/blood MH - Creatine Kinase/blood MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Lipids/blood MH - Male MH - Middle Aged MH - *Primary Health Care EDAT- 2007/02/16 09:00 MHDA- 2007/08/10 09:00 CRDT- 2007/02/16 09:00 PHST- 2007/02/16 09:00 [pubmed] PHST- 2007/08/10 09:00 [medline] PHST- 2007/02/16 09:00 [entrez] AID - 10.1002/pds.1361 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2007 Jun;16(6):652-7. doi: 10.1002/pds.1361. PMID- 17431191 OWN - NLM STAT- MEDLINE DCOM- 20070510 LR - 20070413 IS - 1524-4571 (Electronic) IS - 0009-7330 (Linking) VI - 100 IP - 7 DP - 2007 Apr 13 TI - Triglyceride-rich lipoproteins from normotrygliceridemic subjects and hyperlipidemic patients differently affect endothelial cell activation and gene expression patterns. PG - e81 FAU - Norata, Giuseppe D AU - Norata GD FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Comment PT - Letter PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Lipoproteins) RN - 0 (Triglycerides) SB - IM CON - Circ Res. 2007 Feb 16;100(3):381-90. PMID: 17234968 MH - *Endothelial Cells MH - *Gene Expression MH - Humans MH - Hypertriglyceridemia/blood/genetics/*physiopathology MH - Lipoproteins/*blood/*chemistry MH - Triglycerides/*blood EDAT- 2007/04/14 09:00 MHDA- 2007/05/11 09:00 CRDT- 2007/04/14 09:00 PHST- 2007/04/14 09:00 [pubmed] PHST- 2007/05/11 09:00 [medline] PHST- 2007/04/14 09:00 [entrez] AID - 100/7/e81 [pii] AID - 10.1161/01.RES.0000265132.99997.d3 [doi] PST - ppublish SO - Circ Res. 2007 Apr 13;100(7):e81. doi: 10.1161/01.RES.0000265132.99997.d3. PMID- 16806235 OWN - NLM STAT- MEDLINE DCOM- 20070626 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 191 IP - 2 DP - 2007 Apr TI - Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. PG - 265-71 AB - A strong negative correlation between polyphenols consumption and coronary heart disease has been extensively documented. These results prompted investigations on the mechanisms responsible for polyphenols effects in cardiovascular disease. The aim of this work was to investigate in apoE KO mice the effect of P183/1 (a mixture of cathechin, caffeic acid and resveratrol) on atherosclerosis and gene expression patterns in the vascular wall. ApoE KO mice were fed a diet supplemented with P183/1, 40 and 160 mg/kg body weight/day for 8 weeks. The supplementation with the high dose of P183/1 significantly reduced the presence of atherosclerotic plaque by 40 and 36% in the aortic sinus and in the ascending aorta, respectively. This reduction was associated with a reduced expression of markers for macrophages, lymphocytes (both Th1 and Th2) and of MCP-1, MIP-1alpha, MIP-1beta, CCR1, CCR2 and ET1 in the vascular wall. In conclusion, P183/1 supplementation significantly decreases atherosclerosis in ApoE KO mice by affecting inflammatory cells recruitment and expression of pro-inflammatory chemokines in the vascular wall. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. FAU - Marchesi, Patrizia AU - Marchesi P FAU - Passamonti, Silvia AU - Passamonti S FAU - Pirillo, Angela AU - Pirillo A FAU - Violi, Francesco AU - Violi F FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060627 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Apolipoproteins E) RN - 0 (Caffeic Acids) RN - 0 (Cardiovascular Agents) RN - 0 (Cytokines) RN - 0 (Dietary Fats) RN - 0 (Endothelin-1) RN - 0 (P183-1) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Chemokine) RN - 0 (Stilbenes) RN - 8R1V1STN48 (Catechin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Aorta/drug effects/metabolism/pathology MH - Apolipoproteins E/*deficiency/genetics MH - Atherosclerosis/etiology/genetics/metabolism/pathology/*prevention & control MH - Caffeic Acids/*pharmacology MH - Cardiovascular Agents/*pharmacology MH - Catechin/*pharmacology MH - Cytokines/genetics/metabolism MH - Dietary Fats MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Endothelin-1/genetics/metabolism MH - Gene Expression/*drug effects MH - Mice MH - Mice, Knockout MH - RNA, Messenger/metabolism MH - Receptors, Chemokine/genetics/metabolism MH - Stilbenes/*pharmacology EDAT- 2006/06/30 09:00 MHDA- 2007/06/27 09:00 CRDT- 2006/06/30 09:00 PHST- 2005/12/14 00:00 [received] PHST- 2006/05/10 00:00 [revised] PHST- 2006/05/11 00:00 [accepted] PHST- 2006/06/30 09:00 [pubmed] PHST- 2007/06/27 09:00 [medline] PHST- 2006/06/30 09:00 [entrez] AID - S0021-9150(06)00310-8 [pii] AID - 10.1016/j.atherosclerosis.2006.05.047 [doi] PST - ppublish SO - Atherosclerosis. 2007 Apr;191(2):265-71. doi: 10.1016/j.atherosclerosis.2006.05.047. Epub 2006 Jun 27. PMID- 17446817 OWN - NLM STAT- MEDLINE DCOM- 20070920 LR - 20190319 IS - 1741-8267 (Print) IS - 1741-8267 (Linking) VI - 14 IP - 2 DP - 2007 Apr TI - Averting a pandemic health crisis in Europe by 2020: what physicians need to know regarding cholesterol management. PG - 340-5 AB - BACKGROUND: Cardiovascular disease (CVD) represents a major cause of premature death, disability, and escalating healthcare costs throughout Europe. According to a recent report by the Stockholm Network (an independent European 'think tank'), major political, economic, social, and medical changes are urgently needed with respect to cholesterol management to help prevent CVD. METHODS: To identify key cholesterol management issues that practitioners should consider to help prevent an impending European health crisis, our collective experience of policies and practices relating to CVD and cholesterol management in our respective countries was consolidated and used to develop this commentary. RESULTS: Physicians and healthcare workers are uniquely positioned to make immediate and meaningful improvements in preventing and treating CVD if they recognize and address a handful of key clinical issues pertaining to cholesterol management. These issues include utilizing newer combination therapies and realizing the limitations of statins, improving compliance with cholesterol-lowering therapies, promoting a healthy lifestyle and diet, making treatment decisions based on patients' total CVD risk, fostering communication between primary and secondary providers, and soliciting governmental funding to implement disease management programmes. CONCLUSIONS: By promptly and effectively addressing these cholesterol management issues, physicians and other healthcare professionals have an unprecedented opportunity to help reduce CVD in Europe to lessen the personal, social, and economic impact of this devastating disease. FAU - Catapano, Alberico L AU - Catapano AL AD - Centre for the Study of Atherosclerosis, Marie Curie Training Centre for Cardiovascular Diseases, University of Milan, Milan, Italy. alberico.catapano@unimi.it FAU - Pedersen, Terje R AU - Pedersen TR FAU - de Backer, Guy AU - de Backer G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Eur J Cardiovasc Prev Rehabil JT - European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology JID - 101192000 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cardiovascular Diseases/*blood/drug therapy/*prevention & control MH - Cholesterol/*blood MH - Europe/epidemiology MH - Global Health MH - *Health Knowledge, Attitudes, Practice MH - Health Services Needs and Demand/trends MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Patient Compliance MH - Patient Education as Topic/trends MH - *Physician's Role MH - Primary Prevention/trends MH - Risk Assessment RF - 26 EDAT- 2007/04/21 09:00 MHDA- 2007/09/21 09:00 CRDT- 2007/04/21 09:00 PHST- 2007/04/21 09:00 [pubmed] PHST- 2007/09/21 09:00 [medline] PHST- 2007/04/21 09:00 [entrez] AID - 10.1097/01.hjr.0b013e3280122868 [doi] AID - 00149831-200704000-00026 [pii] PST - ppublish SO - Eur J Cardiovasc Prev Rehabil. 2007 Apr;14(2):340-5. doi: 10.1097/01.hjr.0b013e3280122868. PMID- 17287419 OWN - NLM STAT- MEDLINE DCOM- 20070329 LR - 20171116 IS - 0804-4643 (Print) IS - 0804-4643 (Linking) VI - 156 IP - 2 DP - 2007 Feb TI - Plasma resistin levels correlate with determinants of the metabolic syndrome. PG - 279-84 AB - OBJECTIVE: The role of resistin in insulin sensitivity and obesity is controversial. Some authors suggest that increased serum resistin levels are associated with obesity, visceral fat, insulin resistance, type 2 diabetes and inflammation, while others failed to observe such correlations. The aim of the present study was to investigate the relationship of plasma resistin levels with markers of the metabolic syndrome and atherosclerosis in a large population-based study. DESIGN AND PATIENTS: Plasma resistin levels were determined in 1090 subjects free of any medication selected from the PLIC study (designed to verify the presence of atherosclerotic lesions and progression intima-media thickness (IMT) in the common carotid artery in the general population) and related to the presence of obesity, metabolic syndrome, metabolic abnormalities, cardiovascular risk, and progression of IMT. RESULTS: Plasma resistin levels were highly positively correlated with triglycerides, waist circumference, waist/hip ratio, systolic blood pressure, and ApoAI/ApoB ratio, while they were inversely correlated with high density lipoprotein and ApoAI levels. This finding was gender specific (mainly in women). Plasma resistin levels were significantly higher in women with the metabolic syndrome compared with controls (4.90 (0.24) ng/ml vs 3.90 (0.11) ng/ml; P<0.01), while no difference was observed in obese subjects. Finally, plasma resistin levels were significantly correlated with cardiovascular risk calculated according to the Framingham algorithm (P<0.01). CONCLUSION: Plasma resistin levels are increased in presence of the metabolic syndrome and are associated with increased cardiovascular risk. FAU - Norata, G D AU - Norata GD AD - Centro SISA per lo Studio della Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Milano, Italy. danilo.norata@unimi.it FAU - Ongari, M AU - Ongari M FAU - Garlaschelli, K AU - Garlaschelli K FAU - Raselli, S AU - Raselli S FAU - Grigore, L AU - Grigore L FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PL - England TA - Eur J Endocrinol JT - European journal of endocrinology JID - 9423848 RN - 0 (Resistin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Atherosclerosis/blood/epidemiology MH - Female MH - Humans MH - Insulin Resistance MH - Intra-Abdominal Fat/metabolism MH - Male MH - Metabolic Syndrome/*blood/*epidemiology MH - Middle Aged MH - Obesity/blood/epidemiology MH - Regression Analysis MH - Resistin/*blood MH - Risk Factors MH - Severity of Illness Index EDAT- 2007/02/09 09:00 MHDA- 2007/03/30 09:00 CRDT- 2007/02/09 09:00 PHST- 2007/02/09 09:00 [pubmed] PHST- 2007/03/30 09:00 [medline] PHST- 2007/02/09 09:00 [entrez] AID - 156/2/279 [pii] AID - 10.1530/eje.1.02338 [doi] PST - ppublish SO - Eur J Endocrinol. 2007 Feb;156(2):279-84. doi: 10.1530/eje.1.02338. PMID- 17022864 OWN - NLM STAT- MEDLINE DCOM- 20061024 LR - 20151119 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 22 IP - 10 DP - 2006 Oct TI - Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. PG - 2041-53 AB - OBJECTIVE: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses. RESEARCH DESIGN AND METHODS: Double-blind, multicenter, 6-week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10 mg/day), the next highest (10/40 or 20 mg/day), and maximum doses (10/80 or 40 mg/day). RESULTS: At all doses and across doses, ezetimibe/simvastatin reduced LDL-C levels significantly more (52-61%) than rosuvastatin (46-57%; p < or = 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p < or = 0.005) attained LDL-C levels < 70 mg/dL (1.8 mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (p < 0.001), non-high-density lipoprotein cholesterol (p < 0.001), lipid ratios (p < or = 0.003), and apolipoprotein B (p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (p = 0.004) and next highest (p = 0.006) doses, and across all doses (p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10 mg versus 10/20 mg/day (p = 0.004) and 40 mg versus 10/80 mg/day (p < 0.001). CONCLUSION: Ezetimibe/simvastatin was more effective than rosuvastatin in LDL-C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies. FAU - Catapano, Alberico L AU - Catapano AL AD - University of Milan, Milan, Italy. Alberico.Catapano@unimi.it FAU - Davidson, Michael H AU - Davidson MH FAU - Ballantyne, Christie M AU - Ballantyne CM FAU - Brady, William E AU - Brady WE FAU - Gazzara, Russell A AU - Gazzara RA FAU - Tomassini, Joanne E AU - Tomassini JE FAU - Tershakovec, Andrew M AU - Tershakovec AM LA - eng SI - ClinicalTrials.gov/NCT00090298 PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Cholesterol, LDL) RN - 0 (Drug Combinations) RN - 0 (Ezetimibe, Simvastatin Drug Combination) RN - 0 (Fluorobenzenes) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 0 (Tablets) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - AGG2FN16EV (Simvastatin) SB - IM CIN - Curr Med Res Opin. 2006 Oct;22(10):2037-9. PMID: 17022863 MH - Anticholesteremic Agents/administration & dosage/*therapeutic use MH - Azetidines/administration & dosage/*therapeutic use MH - Cholesterol, LDL/blood MH - Double-Blind Method MH - Drug Combinations MH - Ezetimibe, Simvastatin Drug Combination MH - Female MH - Fluorobenzenes/administration & dosage/*therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*therapeutic use MH - Hypercholesterolemia/blood/*drug therapy MH - Male MH - Middle Aged MH - Pyrimidines/administration & dosage/*therapeutic use MH - Rosuvastatin Calcium MH - Simvastatin/administration & dosage/*therapeutic use MH - Sulfonamides/administration & dosage/*therapeutic use MH - Tablets EDAT- 2006/10/07 09:00 MHDA- 2006/10/25 09:00 CRDT- 2006/10/07 09:00 PHST- 2006/10/07 09:00 [pubmed] PHST- 2006/10/25 09:00 [medline] PHST- 2006/10/07 09:00 [entrez] AID - 10.1185/030079906X132721 [doi] PST - ppublish SO - Curr Med Res Opin. 2006 Oct;22(10):2041-53. doi: 10.1185/030079906X132721. PMID- 16786175 OWN - NLM STAT- MEDLINE DCOM- 20060905 LR - 20161124 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 18 IP - 1 DP - 2006 Jul TI - Oxidized-HDL3 modulates the expression of Cox-2 in human endothelial cells. PG - 209-13 AB - Modified high density lipoprotein (HDL) has been suggested to modulate endothelial expression of proinflammatory genes. Since oxidised HDL (Ox-HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the effect of Ox-HDL3 on the expression of Cox-1 or Cox-2. Ox-HDL3, increased Cox-2 mRNA and protein expression in endothelial cells while no effect on Cox-1 expression was observed. The intracellular pathways involved in this effect were investigated. The incubation with specific inhibitors of intracellular kinases showed that PI3K is mainly involved in the Ox-HDL3-dependent Cox-2 induction. Transient transfection experiments suggested that the NF-IL6 response element in the proximal promoter (-327 to 59) is involved in Ox-HDL3-mediated Cox-2 expression. These data suggest that Ox-HDL induce Cox-2 expression in endothelial cells through a PI3K/NF-IL6-dependent pathway. FAU - Callegari, Elisa AU - Callegari E AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Norata, Giuseppe D AU - Norata GD FAU - Inoue, Hiroyasu AU - Inoue H FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Butadienes) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Imidazoles) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 0 (Morpholines) RN - 0 (Nitriles) RN - 0 (Pyridines) RN - 0 (U 0126) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 1.14.99.1 (Cyclooxygenase 1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - OU13V1EYWQ (SB 203580) SB - IM MH - Butadienes/pharmacology MH - Cells, Cultured MH - Chromones/pharmacology MH - Cyclooxygenase 1/genetics/metabolism MH - Cyclooxygenase 2/genetics/*metabolism MH - Endothelial Cells/*drug effects/metabolism MH - Endothelium, Vascular/cytology/drug effects/metabolism MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation, Enzymologic/drug effects MH - Humans MH - Imidazoles/pharmacology MH - Immunoblotting MH - Lipoproteins, HDL/chemistry/*pharmacology MH - Lipoproteins, HDL3 MH - Morpholines/pharmacology MH - Nitriles/pharmacology MH - Oxidation-Reduction MH - Phosphatidylinositol 3-Kinases/antagonists & inhibitors MH - Pyridines/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Time Factors MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism EDAT- 2006/06/21 09:00 MHDA- 2006/09/06 09:00 CRDT- 2006/06/21 09:00 PHST- 2006/06/21 09:00 [pubmed] PHST- 2006/09/06 09:00 [medline] PHST- 2006/06/21 09:00 [entrez] PST - ppublish SO - Int J Mol Med. 2006 Jul;18(1):209-13. PMID- 16829346 OWN - NLM STAT- MEDLINE DCOM- 20061205 LR - 20131121 IS - 0939-4753 (Print) IS - 0939-4753 (Linking) VI - 16 IP - 5 DP - 2006 Jul TI - Modified HDL: biological and physiopathological consequences. PG - 371-86 AB - Epidemiological and clinical studies have demonstrated the inverse association between HDL cholesterol levels (HDL-C) and the risk of coronary heart disease (CHD). This correlation is believed to relate to the ability of HDL to promote reverse cholesterol transport. Remodeling of HDL due to chemical/physical modifications can dramatically affect its functions, leading to dysfunctional HDL that could promote atherogenesis. HDL modification can be achieved by different means: (i) non-enzymatic modifications, owing to the presence of free metal ions in the atherosclerotic plaques; (ii) cell-associated enzymes, which can degrade the apoproteins without significant changes in the lipid moiety, or can alternatively induce apoprotein cross-linking and lipid oxidation; (iii) association with acute phase proteins, whose circulating levels are significantly increased during inflammation which may modify HDL structure and functions; and (iv) metabolic modifications, such as glycation that occurs under hyperglycaemic conditions. Available data suggest that HDL can easily be modified losing their anti-atherogenic activities. These observation results mainly from in vitro studies, while few in vivo data, are available. Furthermore the in vivo mechanisms involved in HDL modification are ill understood. A better knowledge of these pathways may provide possible therapeutic target aimed at reducing HDL modification. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Italy. FAU - Pirillo, Angela AU - Pirillo A FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Review DEP - 20060623 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Cholesterol, HDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Biological Transport MH - Cholesterol/metabolism MH - Cholesterol, HDL/blood/chemistry/*physiology MH - Coronary Artery Disease/*blood MH - Humans MH - Lipid Peroxidation/*physiology RF - 158 EDAT- 2006/07/11 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/07/11 09:00 PHST- 2005/12/14 00:00 [received] PHST- 2006/01/03 00:00 [accepted] PHST- 2006/07/11 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/07/11 09:00 [entrez] AID - S0939-4753(06)00005-6 [pii] AID - 10.1016/j.numecd.2006.01.012 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2006 Jul;16(5):371-86. doi: 10.1016/j.numecd.2006.01.012. Epub 2006 Jun 23. PMID- 16721205 OWN - NLM STAT- MEDLINE DCOM- 20061026 LR - 20151119 IS - 1558-2027 (Print) IS - 1558-2027 (Linking) VI - 7 IP - 6 DP - 2006 Jun TI - Secondary prevention of myocardial infarction: a survey in primary care. PG - 422-6 AB - OBJECTIVE: To collect information on the major risk factors and secondary prevention among patients with myocardial infarction in Italy. METHODS: Data were obtained from the database of the Italian College of General Practitioners; 3588 patients (mean age 68.7 +/- 11.3 years; 2698 men, 888 women; two unrecorded gender), with an average time from event of 6 +/- 5.7 years, were identified. RESULTS: Among the major risk factors, data entry ranged from 50.3% for physical activity to 74.9% for blood pressure. Inadequate blood pressure control was present in 49.2% and elevated plasma cholesterol levels (> 5.2 mmol/l) in 57.3%; among the latter group, 65% were on lipid-lowering therapy. Only 47.2% of the treated patients achieved a total cholesterol level of < 5.2 mmol/l. Antiplatelet or anticoagulant drugs, beta-blockers, and angiotensin-converting enzyme inhibitors were prescribed to 43%, 10.3%, and 57.9% of patients, respectively. CONCLUSIONS: The preventive attitude of Italian general practitioners is similar to that reported in other European countries with two noticeable exceptions: under-prescription of beta-blockers and of antiplatelet drugs. Clearly, secondary prevention requires major improvement. FAU - Filippi, Alessandro AU - Filippi A AD - Italian College of General Practitioners, Florence, Italy. FAU - Vanuzzo, Diego AU - Vanuzzo D FAU - Bignamini, Angelo A AU - Bignamini AA FAU - Mazzaglia, Gianpiero AU - Mazzaglia G FAU - Brignoli, Ovidio AU - Brignoli O FAU - Sabatini, Andrea AU - Sabatini A FAU - Cricelli, Claudio AU - Cricelli C FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PL - United States TA - J Cardiovasc Med (Hagerstown) JT - Journal of cardiovascular medicine (Hagerstown, Md.) JID - 101259752 RN - 0 (Anticoagulants) RN - 0 (Lipids) RN - 0 (Platelet Aggregation Inhibitors) SB - IM MH - Adult MH - Aged MH - Anticoagulants/administration & dosage MH - Female MH - Humans MH - Italy MH - Lipids/blood MH - Male MH - Middle Aged MH - Myocardial Infarction/*prevention & control MH - Platelet Aggregation Inhibitors/administration & dosage MH - Practice Patterns, Physicians'/*statistics & numerical data MH - *Primary Health Care MH - Risk Factors EDAT- 2006/05/25 09:00 MHDA- 2006/10/27 09:00 CRDT- 2006/05/25 09:00 PHST- 2006/05/25 09:00 [pubmed] PHST- 2006/10/27 09:00 [medline] PHST- 2006/05/25 09:00 [entrez] AID - 10.2459/01.JCM.0000228693.07279.a1 [doi] AID - 01244665-200606000-00008 [pii] PST - ppublish SO - J Cardiovasc Med (Hagerstown). 2006 Jun;7(6):422-6. doi: 10.2459/01.JCM.0000228693.07279.a1. PMID- 16675737 OWN - NLM STAT- MEDLINE DCOM- 20060621 LR - 20171116 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 37 IP - 6 DP - 2006 Jun TI - Effects of fractalkine receptor variants on common carotid artery intima-media thickness. PG - 1558-61 AB - BACKGROUND AND PURPOSE: Fractalkine receptor (CX3CR1) plays a key role during atherogenesis. CX3CR1 has 2 common coding polymorphisms, namely V249I and T280M, that have been associated with interindividual differences in susceptibility to atherosclerosis. In the present study, we investigated the possible association between CX3CR1variants and intima-media thickness (IMT). METHODS: We genotyped 1256 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study) for the presence of the V249 and the M280 variants of CX3CR1. RESULTS: Significantly reduced IMT was observed in subjects with the MM280 genotype (0.57+/-0.12 mm) compared with subjects with the TT (0.65+/-0.14 mm) or the TM (0.65+/-0.13 mm) genotype. No difference in IMT was observed within carrier of the II249, VI249, or VV249 genotype. Subjects with combined genotype VI249/MM280 and II249/MM280 showed a reduced IMT. CONCLUSIONS: The presence of the M280 polymorphism of the fractalkine receptor is associated with a decreased common carotid artery IMT, whereas the presence of the I249 polymorphism does not play a major role on the progression of carotid atherosclerosis. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Italy. Danilo.Norata@unimi.it FAU - Garlaschelli, Katia AU - Garlaschelli K FAU - Ongari, Manuele AU - Ongari M FAU - Raselli, Sara AU - Raselli S FAU - Grigore, Liliana AU - Grigore L FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060504 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (CX3C Chemokine Receptor 1) RN - 0 (Receptors, Cytokine) RN - 0 (Receptors, HIV) SB - IM MH - Adult MH - Aged MH - CX3C Chemokine Receptor 1 MH - Carotid Artery, Common/*diagnostic imaging MH - Cohort Studies MH - Female MH - *Genetic Variation MH - Genotype MH - Humans MH - Intracranial Arteriosclerosis/*diagnostic imaging/*genetics MH - Male MH - Middle Aged MH - Polymorphism, Genetic MH - Receptors, Cytokine/*genetics MH - Receptors, HIV/*genetics MH - Tunica Intima/*diagnostic imaging MH - Tunica Media/*diagnostic imaging MH - Ultrasonography EDAT- 2006/05/06 09:00 MHDA- 2006/06/22 09:00 CRDT- 2006/05/06 09:00 PHST- 2006/05/06 09:00 [pubmed] PHST- 2006/06/22 09:00 [medline] PHST- 2006/05/06 09:00 [entrez] AID - 01.STR.0000221803.16897.22 [pii] AID - 10.1161/01.STR.0000221803.16897.22 [doi] PST - ppublish SO - Stroke. 2006 Jun;37(6):1558-61. doi: 10.1161/01.STR.0000221803.16897.22. Epub 2006 May 4. PMID- 16775502 OWN - NLM STAT- MEDLINE DCOM- 20061106 LR - 20111117 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 47 IP - 5 DP - 2006 May TI - In human endothelial cells amino acids inhibit insulin-induced Akt and ERK1/2 phosphorylation by an mTOR-dependent mechanism. PG - 643-9 AB - In several cellular systems, amino acids synergize with insulin in promoting protein synthesis through the activation of the protein kinases p70/S6-K and PHAS-1. Such activations are mediated by the upstream kinase: mammalian target of rapamycin (mTor). In this work we have investigated the intracellular pathways involved in insulin-induced and amino acid-induced p70/S6-K activations in human endothelial cells. In human umbilical vein endothelial cells, insulin induces the phosphorylation of p70/S6-K at 5 minutes decreasing thereafter, whereas amino acids alone or associated with insulin phosphorylate p70/S6-K at all the time points analyzed (60 minutes). Insulin and amino acids phosphorylate p70/S6-K by mTor-dependent and phosphotidylinositol 3-kinase-dependent mechanisms, whereas the mitogen-activated protein kinase pathway is involved only when p70/S6-K is activated by insulin. Insulin induces the phosphorylation of Akt and extracellular signal-regulated protein kinase (ERK) 1/2, whereas amino acids did not. Moreover, amino acids suppress the phosphorylations induced by insulin. The inhibitory effects of amino acids are reverted by the mTor inhibitor rapamycin. Insulin-induced phosphorylation of Akt (at 15 and 30 minutes) is not accompanied by the phosphorylation of the downstream kinase p70/S6-K, indicating the existence of a negative feedback at this level. Our data demonstrate that at the level of human endothelial cells, amino acids synergize with insulin in the phosphorylation of the kinase that lies downstream mTor, as p70/S6-K, whereas they inhibit the upstream kinases Akt and extracellular signal-regulated protein kinase 1/2 when activated by insulin, by an mTor-dependent mechanism. FAU - Pellegatta, Fabio AU - Pellegatta F AD - Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, Milan, Italy. fabio.pellegatta@unimi.it FAU - Catapano, Alberico Luigi AU - Catapano AL FAU - Luzi, Livio AU - Luzi L FAU - Terruzzi, Ileana AU - Terruzzi I LA - eng PT - Journal Article PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Amino Acids) RN - 0 (Insulin) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Amino Acids/*pharmacology MH - Cells, Cultured MH - Endothelial Cells/*drug effects/metabolism MH - Humans MH - Insulin/*pharmacology MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Phosphorylation MH - Protein Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - TOR Serine-Threonine Kinases EDAT- 2006/06/16 09:00 MHDA- 2006/11/07 09:00 CRDT- 2006/06/16 09:00 PHST- 2006/06/16 09:00 [pubmed] PHST- 2006/11/07 09:00 [medline] PHST- 2006/06/16 09:00 [entrez] AID - 10.1097/01.fjc.0000211751.01326.fa [doi] AID - 00005344-200605000-00003 [pii] PST - ppublish SO - J Cardiovasc Pharmacol. 2006 May;47(5):643-9. doi: 10.1097/01.fjc.0000211751.01326.fa. PMID- 16516917 OWN - NLM STAT- MEDLINE DCOM- 20060613 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 40 IP - 4 DP - 2006 Apr TI - Triglyceride-rich lipoproteins from hypertriglyceridemic subjects induce a pro-inflammatory response in the endothelium: Molecular mechanisms and gene expression studies. PG - 484-94 AB - Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study we investigated the effects of TGRLs from type IV hyperlipidemic and normolipidemic subjects on endothelial activation focusing on the effects on intracellular pathways and gene expression. A total of 54 subjects, 30 hypertriglyceridemic (triglyceride (TG) levels 284+/-101 mg/dl) and 23 normotriglyceridemic (TG levels 109+/-40 mg/dl) were enrolled as lipoprotein donors. TGRLs were isolated from hypertriglyceridemic (H-TGRL) and normotriglyceridemic (N-TGRL) subjects. RNA from human endothelial cells incubated with N-TGRL or H-TGRL was prepared for cDNA microarray analyses. Western blotting was used to study intracellular signaling pathways. Regulated genes were further studied with real-time PCR, immunofluorescence and FACS. Furthermore, a protein/DNA array and chromatin-immunoprecipitation were used to identify transcription factors involved in the observed effects. Both N-TGRL and H-TGRL activated ERK1/2 and p38 MAPK. However, there were differences in the pattern of upregulated target genes between the two types of lipoproteins in HUVECs and/or HAECs: PAI-1, VCAM-1, ELAM-1 and MCP-1 were upregulated by both N-TGRL and H-TGRL, while PECAM-1, IL-6 and ADAMTs1 were selectively upregulated by H-TGRL. Chromatin immunoprecipitation analysis demonstrated the involvement of transcription factors NF-kB and CREB in the activation of these genes. These results support the possible involvement of hypertriglyceridemic TGRLs in endothelial dysfunction via induction of a pro-inflammatory and pro-thrombotic state. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. FAU - Grigore, L AU - Grigore L FAU - Raselli, S AU - Raselli S FAU - Seccomandi, P M AU - Seccomandi PM FAU - Hamsten, A AU - Hamsten A FAU - Maggi, F M AU - Maggi FM FAU - Eriksson, P AU - Eriksson P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060306 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Lipoproteins) RN - 0 (Triglycerides) SB - IM MH - Adult MH - Cells, Cultured MH - Endothelial Cells/*metabolism/pathology MH - Endothelium, Vascular/*metabolism/pathology MH - Gene Expression Profiling/methods MH - *Gene Expression Regulation/drug effects MH - Humans MH - Hyperuricemia/*metabolism/pathology MH - Lipoproteins/*metabolism/pharmacology MH - Male MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis/methods MH - Signal Transduction/drug effects MH - Triglycerides/*metabolism/pharmacology EDAT- 2006/03/07 09:00 MHDA- 2006/06/14 09:00 CRDT- 2006/03/07 09:00 PHST- 2005/04/26 00:00 [received] PHST- 2006/01/25 00:00 [revised] PHST- 2006/01/26 00:00 [accepted] PHST- 2006/03/07 09:00 [pubmed] PHST- 2006/06/14 09:00 [medline] PHST- 2006/03/07 09:00 [entrez] AID - S0022-2828(06)00033-2 [pii] AID - 10.1016/j.yjmcc.2006.01.022 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2006 Apr;40(4):484-94. doi: 10.1016/j.yjmcc.2006.01.022. Epub 2006 Mar 6. PMID- 16647293 OWN - NLM STAT- MEDLINE DCOM- 20060717 LR - 20171213 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1761 IP - 3 DP - 2006 Mar TI - 15-Lipoxygenase-mediated modification of high-density lipoproteins impairs SR-BI- and ABCA1-dependent cholesterol efflux from macrophages. PG - 292-300 AB - Elevated plasma levels of high-density lipoprotein cholesterol (HDL-C) are atheroprotective and HDL-dependent reverse cholesterol transport has been related to this effect. HDL particles may, however, undergo modifications that affect their biological activities. Lipoxygenases (LOs) belong to a family of lipid peroxidizing enzymes; among them, reticulocyte-type 15-lipoxygenase (15-LO-1) appears to play a pathophysiological role in atherosclerosis, as its expression is increased in atherosclerotic plaques and it has been shown to oxidize low-density lipoproteins to an atherogenic form. In this work we investigated the impact of in vitro 15-lipoxygenase-catalyzed modification of HDL3 on their ability to act as cholesterol acceptor and found that 15-LO-modified HDL3 were less effective in mediating cholesterol efflux from lipid-laden J774 cells. A reduced binding of 15-LO-modified HDL3 to scavenger receptor class B, type I (SR-BI), due to HDL apoproteins cross-linking, explained, at least in part, the observed reduction of cholesterol efflux. In addition, ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux was also reduced, as a consequence of pre-beta-particles loss after HDL3 modification. These results suggest that 15-lipoxygenase might induce structural alterations of HDL3 particles that impair their capability of triggering reverse cholesterol transport. FAU - Pirillo, Angela AU - Pirillo A AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. angela.pirillo@unimi.it FAU - Uboldi, Patrizia AU - Uboldi P FAU - Kuhn, Hartmut AU - Kuhn H FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060407 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (ABCA1 protein, human) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Lipoproteins, HDL) RN - 0 (Scarb1 protein, mouse) RN - 0 (Scavenger Receptors, Class B) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 66106-91-0 (cholesteryl oleyl ether) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) SB - IM MH - ATP Binding Cassette Transporter 1 MH - ATP-Binding Cassette Transporters/*metabolism MH - Animals MH - Arachidonate 15-Lipoxygenase/*metabolism MH - Cell Line MH - Cholesterol/analogs & derivatives/*metabolism MH - Humans MH - Lipoproteins, HDL/*metabolism MH - Macrophages/cytology/*metabolism MH - Mice MH - Rabbits MH - Scavenger Receptors, Class B/*metabolism MH - Thiobarbituric Acid Reactive Substances/metabolism EDAT- 2006/05/02 09:00 MHDA- 2006/07/18 09:00 CRDT- 2006/05/02 09:00 PHST- 2005/09/20 00:00 [received] PHST- 2006/03/14 00:00 [revised] PHST- 2006/03/14 00:00 [accepted] PHST- 2006/05/02 09:00 [pubmed] PHST- 2006/07/18 09:00 [medline] PHST- 2006/05/02 09:00 [entrez] AID - S1388-1981(06)00071-0 [pii] AID - 10.1016/j.bbalip.2006.03.009 [doi] PST - ppublish SO - Biochim Biophys Acta. 2006 Mar;1761(3):292-300. doi: 10.1016/j.bbalip.2006.03.009. Epub 2006 Apr 7. PMID- 16391816 OWN - NLM STAT- MEDLINE DCOM- 20060302 LR - 20061115 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 17 IP - 2 DP - 2006 Feb TI - In vitro isolation of circulating endothelial progenitor cells is related to the high density lipoprotein plasma levels. PG - 203-8 AB - Circulating endothelial progenitor cells (EPCs) play an important role in post natal neovascularization. High density lipoproteins (HDL) protect the vascular wall from atherosclerosis. The role exerted by HDL on EPCs physiology is unknown. In this study we investigated whether the levels of plasma HDL can modulate the number of EPCs. The number of EPCs was evaluated in 24 subjects as the number of endothelial colony-forming unit (e-CFU) growth in culture. The number of AC133 positive progenitor cells present in the gate of the CD34 bright positive lymphocytes was also evaluated. Plasma levels of HDL, triglycerides and total cholesterol/HDL cholesterol ratio correlated with the number of e-CFU (r=0.62, P=0.006; r=-0.54, P=0.019, and r=-0.61, P=0.007 respectively), but not with the number of CD34/AC133 positive progenitor cells. In vitro, the incubation of the mononuclear cellular fraction with HDL did not increase the number of e-CFU in culture, whereas LDL and VLDL reduced the number of e-CFU. Our results indicate that human HDL plasma levels directly relate to the number of circulating endothelial progenitor cells that can be isolated in vitro, as determined by the number of e-CFU. FAU - Pellegatta, Fabio AU - Pellegatta F AD - Department of Pharmacological Sciences, University of Milan, I-20132 Milan, Italy. FAU - Bragheri, Marta AU - Bragheri M FAU - Grigore, Liliana AU - Grigore L FAU - Raselli, Sara AU - Raselli S FAU - Maggi, Franco Maria AU - Maggi FM FAU - Brambilla, Claudia AU - Brambilla C FAU - Reduzzi, Alice AU - Reduzzi A FAU - Pirillo, Angela AU - Pirillo A FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Lipoproteins, HDL) SB - IM MH - Cell Movement MH - Cell Separation MH - Cells, Cultured MH - Endothelial Cells/*cytology/*metabolism MH - Humans MH - Lipoproteins, HDL/*blood MH - Middle Aged MH - Phenotype MH - Stem Cells/*cytology/*metabolism EDAT- 2006/01/05 09:00 MHDA- 2006/03/03 09:00 CRDT- 2006/01/05 09:00 PHST- 2006/01/05 09:00 [pubmed] PHST- 2006/03/03 09:00 [medline] PHST- 2006/01/05 09:00 [entrez] PST - ppublish SO - Int J Mol Med. 2006 Feb;17(2):203-8. PMID- 16317058 OWN - NLM STAT- MEDLINE DCOM- 20060314 LR - 20171116 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 91 IP - 2 DP - 2006 Feb TI - Dihydrotestosterone decreases tumor necrosis factor-alpha and lipopolysaccharide-induced inflammatory response in human endothelial cells. PG - 546-54 AB - CONTEXT: An increasing body of evidence suggests that testosterone may exert beneficial effects on the development of atherosclerosis. It was suggested that testosterone may act after conversion into estradiol and activation of the estrogen receptors; however, a direct role of androgens on the vascular wall has been proposed. OBJECTIVE: We investigated the effects of dihydrotestosterone on the proinflammatory response observed in human endothelial cells. DESIGN: Human endothelial cells isolated from umbilical cords were incubated with lipopolysaccharide or TNFalpha in the presence or absence of dihydrotestosterone (DHT). mRNA and cellular proteins were processed for gene expression studies, and transient transfection experiments were performed to investigate molecular mechanisms involved in the effects observed. SETTING: These studies took place at the Department of Pharmacological Sciences, University of Milan, Milan, Italy. RESULTS: Lipopolysaccharide and TNFalpha induced VCAM-1 and ICAM-1 mRNA and protein expression, as detected by real-time quantitative PCR, fluorescence-activated cell sorting, and confocal microscopy, but this effect was inhibited when cells were incubated with DHT. In addition, DHT inhibited mRNA expression of IL-6, MCP-1, CD40, TLR4, PAI-1, and Cox-2 and the release of cytokines and chemokines such as GRO, granulocyte-macrophage colony-stimulating factor, and TNF. The DHT effect was counteracted by bicalutamide, an antagonist of the androgen receptor. Furthermore, when cells were cotransfected with a Cox-2 promoter or a 3X-NF-kappaB luciferase reporter vector and a plasmid expressing the human androgen receptor, DHT treatment inhibited the increase of the luciferase activity observed with TNFalpha. CONCLUSION: DHT could positively regulate endothelial function through the control of the inflammatory response mediated by nuclear factor-kappaB in endothelial cells. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Italy, Via Balzaretti 9, 20133 Milan, Italy. Danilo.Norata@unimi.it FAU - Tibolla, Gianpaolo AU - Tibolla G FAU - Seccomandi, Paul Maria AU - Seccomandi PM FAU - Poletti, Angelo AU - Poletti A FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051129 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Androgen Antagonists) RN - 0 (Androgen Receptor Antagonists) RN - 0 (Anilides) RN - 0 (E-Selectin) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Nitriles) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Androgen) RN - 0 (Tosyl Compounds) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 08J2K08A3Y (Dihydrotestosterone) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - A0Z3NAU9DP (bicalutamide) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - AIM SB - IM MH - Androgen Antagonists/pharmacology MH - Androgen Receptor Antagonists MH - Anilides/pharmacology MH - Cell Line, Tumor MH - Cyclooxygenase 2/biosynthesis/genetics MH - Dihydrotestosterone/*pharmacology MH - Drug Interactions MH - E-Selectin/biosynthesis/genetics MH - Endothelial Cells/*drug effects/immunology/metabolism MH - Humans MH - Immunoblotting MH - Inflammation/drug therapy/metabolism MH - Intercellular Adhesion Molecule-1/biosynthesis/genetics MH - Lipopolysaccharides/*pharmacology MH - NF-kappa B/metabolism MH - Nitriles MH - Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis/genetics MH - RNA, Messenger/biosynthesis/genetics MH - Receptors, Androgen/immunology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tosyl Compounds MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Vascular Cell Adhesion Molecule-1/biosynthesis/genetics EDAT- 2005/12/01 09:00 MHDA- 2006/03/15 09:00 CRDT- 2005/12/01 09:00 PHST- 2005/12/01 09:00 [pubmed] PHST- 2006/03/15 09:00 [medline] PHST- 2005/12/01 09:00 [entrez] AID - jc.2005-1664 [pii] AID - 10.1210/jc.2005-1664 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2006 Feb;91(2):546-54. doi: 10.1210/jc.2005-1664. Epub 2005 Nov 29. PMID- 16755158 OWN - NLM STAT- MEDLINE DCOM- 20061103 LR - 20171116 IS - 0253-5068 (Print) IS - 0253-5068 (Linking) VI - 24 IP - 4 DP - 2006 TI - Role of vitamin E-coated membrane in reducing advanced glycation end products in hemodialysis patients: a pilot study. PG - 369-76 AB - INTRODUCTION: Advanced glycation end products (AGEs) are markers of oxidative stress. AIMS: To assess if a vitamin-E-coated dialyzer affects plasma AGE levels and endothelial function in hemodialysis patients. METHODS: 16 patients were dialyzed with a synthetic modified cellulose membrane (SMC, n = 8) or a vitamin E-coated dialyzer (n = 8), respectively. At week 32 endothelial function was determined as brachial artery flow-mediated dilatation (FMD). Total AGEs, free pentosidine (FP), protein-bound pentosidine (BP) and autoantibodies against oxidized LDL (ox-LDL-autoantibodies) were assessed at baseline (T0) and at 16, 32, 40 and 42 weeks (T16, T32, T40 and T42). RESULTS: At T16 and T32 FP and BP were lower in vitamin E than in SMC (T 16: 88.7 +/- 8.96 vs. 124.2 +/- 11.90 pmol/ml plasma; p = 0.04, and 22.9 +/- 2.99 vs. 32.8 +/- 2.98 pmol/mg proteins; p = 0.04. T32: 78.7 +/- 8.54 vs. 123.7 +/- 10.15 pmol/ml plasma; p = 0.007, and 19.9 +/- 2.0 vs. 33.67 +/- 2.41 pmol/mg proteins; p = 0.001). In vitamin E, AGEs were lower at T32, T40 and T42 (946.7 +/- 80.91 vs. 1,351.2 +/- 179.33 AU/ml, p = 0.05; 986.9 +/- 59.63 vs. 1,509.9 +/- 154.17 AU/ml, p = 0.013; 890.3 +/- 73.70 vs. 1,453.9 +/- 153.16 AU/ml, p = 0.009). At T32 AGEs, ox-LDL autoantibodies and FMD were inversely correlated (R = -0.70 p = 0.007 and R = -0.59, p = 0.04, respectively). CONCLUSIONS: Vit E-coated membrane reduces plasma AGEs levels and AGEs values are negatively correlated with FMD. CI - Copyright 2006 S. Karger AG, Basel. FAU - Baragetti, I AU - Baragetti I AD - Department of Medicine, Division of Nephrology and Dialysis, Cinisello Balsamo, University of Milan, Milan, Italy. i.baragetti@bassini.hsgerardo.org FAU - Furiani, S AU - Furiani S FAU - Vettoretti, S AU - Vettoretti S FAU - Raselli, S AU - Raselli S FAU - Maggi, F M AU - Maggi FM FAU - Galli, F AU - Galli F FAU - Catapano, A L AU - Catapano AL FAU - Buccianti, G AU - Buccianti G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060601 PL - Switzerland TA - Blood Purif JT - Blood purification JID - 8402040 RN - 0 (Antioxidants) RN - 0 (Glycation End Products, Advanced) RN - 0 (Lipoproteins, LDL) RN - 0 (Membranes, Artificial) RN - 0LVT1QZ0BA (Homocysteine) RN - 1406-18-4 (Vitamin E) RN - 94ZLA3W45F (Arginine) RN - BJ4I2X2CQJ (pentosidine) RN - K3Z4F929H6 (Lysine) SB - IM CIN - Blood Purif. 2006;24(4):367-8. PMID: 16755157 MH - Aged MH - Analysis of Variance MH - Antioxidants/*pharmacology MH - Arginine/analogs & derivatives/blood MH - Brachial Artery/drug effects/physiopathology MH - Endothelium, Vascular/drug effects/physiopathology MH - Female MH - Glycation End Products, Advanced/*blood MH - Homocysteine/drug effects MH - Humans MH - Linear Models MH - Lipoproteins, LDL/immunology MH - Lysine/analogs & derivatives/blood MH - Male MH - *Membranes, Artificial MH - Middle Aged MH - Oxidative Stress/drug effects MH - Pilot Projects MH - *Renal Dialysis MH - Vasodilation/drug effects/physiology MH - Vitamin E/*pharmacology EDAT- 2006/06/07 09:00 MHDA- 2006/11/04 09:00 CRDT- 2006/06/07 09:00 PHST- 2005/09/09 00:00 [received] PHST- 2006/02/24 00:00 [accepted] PHST- 2006/06/07 09:00 [pubmed] PHST- 2006/11/04 09:00 [medline] PHST- 2006/06/07 09:00 [entrez] AID - 93678 [pii] AID - 10.1159/000093678 [doi] PST - ppublish SO - Blood Purif. 2006;24(4):369-76. doi: 10.1159/000093678. Epub 2006 Jun 1. PMID- 16142410 OWN - NLM STAT- MEDLINE DCOM- 20051221 LR - 20181201 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 16 IP - 4 DP - 2005 Oct TI - Liver X receptor and retinoic X receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells. PG - 717-22 AB - The cooperation of liver X receptors (LXRs) alpha and beta, and retinoic X receptor (RXR) modulate the expression of several genes involved in lipid metabolism in hepatocyte and macrophages. Using cDNA microarray technology, we have shown previously that several of these genes are also expressed in endothelial cells. In the present study, we investigated whether the activation of LXR and RXR affects the expression of genes involved in lipid metabolism in human endothelial cells. Relative expression of ABCA-1, CETP, SR-B1, EL, LPL, PLTP, ApoE and LDLR was investigated in HUVECs, human fibroblasts (hFB) and HepG2 cells by quantitative real-time PCR. For CETP and EL mRNA expression, the results were HUVECs > hFB > HEPG2; for PLTP, LDLR and LPL: hFB > HUVECs > HEPG2; for SR-B1 and ApoE: HEPG2 > HUVECs > hFB; and for ABCA-1 HEPG2: > hFB > HUVECs. Incubation of HUVECs with LXR agonists as 22-(R)-hydroxycholesterol (22-(R)-HC) or T0901317-induced ABCA1 (20.1- and 17.8-fold), LPL (3.46- and 7.03-fold) and CETP (6.34- and 3.98-fold) expression; EL, LDLR and SR-B1 expression was induced only upon incubation with T0901317 (2.40-, 2.83- and 2.19-fold, respectively) while 22-(R)-HC had no effect on EL and SR-B1 expression (0.8- and 0.9-fold) and decreased LDLR expression (0.4-fold). No effect of either 22-(R)-HC or T0901317 on PLTP and ApoE expression was observed. The RXR agonist, 9-cis retinoic acid (9CRA) alone induced the expression of CETP, LPL and SR-B1 (2.8-, 8.2- and 2.4-fold). No effect of 9CRA on ABCA-1, EL, PLTP, ApoE, and LDLR expression was observed. Association of 9CRA with 22-(R)-HC or T0901317 increased the expression of CETP and LPL while no effect on ABCA-1 or LDLR was observed. Activation of LXRs and RXRs in endothelial cells represents a new target of LXR and RXR agonist in the arterial wall. Modulation of gene expression in the endothelium should be taken into account when studying the effects of LXR and RXR agonists on lipid metabolism in the arterial wall. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. FAU - Ongari, M AU - Ongari M FAU - Uboldi, P AU - Uboldi P FAU - Pellegatta, F AU - Pellegatta F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (ABCA1 protein, human) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (CETP protein, human) RN - 0 (Carrier Proteins) RN - 0 (Cholesterol Ester Transfer Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Glycoproteins) RN - 0 (Hydrocarbons, Fluorinated) RN - 0 (Hydroxycholesterols) RN - 0 (Liver X Receptors) RN - 0 (Orphan Nuclear Receptors) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Retinoid X Receptors) RN - 0 (SCARB1 protein, human) RN - 0 (Scavenger Receptors, Class B) RN - 0 (Sulfonamides) RN - 0 (TO-901317) RN - 17711-16-9 (22-hydroxycholesterol) RN - 1UA8E65KDZ (Alitretinoin) RN - 5688UTC01R (Tretinoin) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - ATP Binding Cassette Transporter 1 MH - ATP-Binding Cassette Transporters/genetics/metabolism MH - Alitretinoin MH - Blotting, Western MH - Carrier Proteins/genetics/metabolism MH - Cell Line MH - Cell Line, Tumor MH - Cells, Cultured MH - Cholesterol Ester Transfer Proteins MH - DNA-Binding Proteins/*agonists/metabolism MH - Endothelial Cells/cytology/*drug effects/metabolism MH - Gene Expression/*drug effects MH - Glycoproteins/genetics/metabolism MH - Humans MH - Hydrocarbons, Fluorinated MH - Hydroxycholesterols/pharmacology MH - *Lipid Metabolism MH - Lipoprotein Lipase/genetics/metabolism MH - Liver X Receptors MH - Orphan Nuclear Receptors MH - RNA, Messenger/genetics/metabolism MH - Receptors, Cytoplasmic and Nuclear/*agonists/metabolism MH - Retinoid X Receptors/*agonists/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Scavenger Receptors, Class B/genetics/metabolism MH - Sulfonamides/pharmacology MH - Tretinoin/pharmacology EDAT- 2005/09/06 09:00 MHDA- 2005/12/22 09:00 CRDT- 2005/09/06 09:00 PHST- 2005/09/06 09:00 [pubmed] PHST- 2005/12/22 09:00 [medline] PHST- 2005/09/06 09:00 [entrez] PST - ppublish SO - Int J Mol Med. 2005 Oct;16(4):717-22. PMID- 23361603 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20130131 LR - 20181113 IS - 1120-9879 (Print) IS - 1120-9879 (Linking) VI - 12 IP - 3 DP - 2005 Sep TI - Global cardiovascular risk : the role of plasma lipids. PG - 125-33 LID - 10.2165/00151642-200512030-00003 [doi] AB - Atherosclerosis is a multifactorial disease. This is supported by a large body of clinical and experimental data collected during the last 30 years, either in observational or in interventional clinical trials. During these years, a large number of risk factors and clinical conditions, closely related to the development of atherosclerosis, have been identified. The most relevant risk factors for cardiovascular disease are hyperlipidaemia, arterial hypertension, diabetes mellitus, cigarette smoking and family history.Cardiovascular risk factors interact with each other in a complex, and not fully elucidated fashion, contributing to the definition of a 'global cardiovascular risk profile'. Thus, the cardiovascular risk profile must be evaluated (through algorithms or risk charts) for each individual. Patients presenting with multiple cardiovascular risk factors have a higher risk of developing a major cardiovascular event, and in these patients a strict control of risk factors leads to an effective prevention of cardiovascular disease.In this latter regard, hypercholesterolemia deserves a 'dynamic' role. The most recent guidelines for the management of patients with hyperlipidaemia underscore the need for a more strict metabolic control in patients with prior cardiovascular events (secondary prevention), and also in patients with no evidence of cardiovascular disease (primary prevention), in which the concomitant presence of multiple risk factors or diabetes confers a high risk (e.g. patients with previous myocardial infarction or stroke). FAU - Catapano, Alberico L AU - Catapano AL AD - Department of Pharmacological Sciences, Director Center for the Study of Atherosclerosis, Marie Curie Training Centre for Cardiovascular Diseases, University of Milan, Via G. Balzaretti 9-20133, Milan, Italy, Alberico.Catapano@unimi.it. FAU - Catapano, Luca AU - Catapano L LA - eng PT - Journal Article PL - New Zealand TA - High Blood Press Cardiovasc Prev JT - High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension JID - 9421087 EDAT- 2005/09/01 00:00 MHDA- 2005/09/01 00:01 CRDT- 2013/01/31 06:00 PHST- 2013/01/31 06:00 [entrez] PHST- 2005/09/01 00:00 [pubmed] PHST- 2005/09/01 00:01 [medline] AID - 10.2165/00151642-200512030-00003 [doi] PST - ppublish SO - High Blood Press Cardiovasc Prev. 2005 Sep;12(3):125-33. doi: 10.2165/00151642-200512030-00003. PMID- 15953129 OWN - NLM STAT- MEDLINE DCOM- 20050719 LR - 20171116 IS - 0954-6820 (Print) IS - 0954-6820 (Linking) VI - 258 IP - 1 DP - 2005 Jul TI - Effect of the Toll-like receptor 4 (TLR-4) variants on intima-media thickness and monocyte-derived macrophage response to LPS. PG - 21-7 AB - OBJECTIVES: Toll-like receptor 4 (TLR-4) is believed to contribute to the initiation and progression of atherosclerosis. The association of the D299G polymorphism of the TLR-4 gene with the progression of coronary and carotid atherosclerosis, risk of cardiovascular events and myocardial infarction is controversial. We have investigated whether the presence of the D299G polymorphism and the co-segregated T399I polymorphism affects the intima-media thickness (IMT) in the general population. SUBJECTS: The PLIC study population (n = 1256) was genotyped for the D299G and the T399I polymorphisms. RESULTS: The presence of both the D299G and T399I alleles was observed in the 13.0% of the population, carriers of the T399I alone were 1.8% and of the D299G alone were 0.9%. No difference in IMT was detected within the carriers of the D299G and T399I alleles and the wild-type subjects in the PLIC population. Furthermore, we investigated whether monocyte from D299G to T399I subjects present a defective response to CD40, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, cyclo-oxygenase (COX)-2 and PTX3 expression induced by lipopolysaccharide (LPS). When the monocyte-derived macrophages of these subjects were challenged with LPS (1 mug mL(-1)), no impact of the polymorphisms on the induction of CD40, MCP-1 and PTX3 was observed. Only IL-6 and COX-2 induction by LPS resulted reduced in the D299G/T399I carriers. CONCLUSION: The presence of the D299G and T399I polymorphisms of the TLR-4 gene does not play a major role on the progression of carotid atherosclerosis. Macrophages from the subjects carrying the polymorphisms show an impaired response to LPS limited only to a IL-6 and COX-2. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Garlaschelli, K AU - Garlaschelli K FAU - Ongari, M AU - Ongari M FAU - Raselli, S AU - Raselli S FAU - Grigore, L AU - Grigore L FAU - Benvenuto, F AU - Benvenuto F FAU - Maggi, F M AU - Maggi FM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 RN - 0 (CCL2 protein, human) RN - 0 (CD40 Antigens) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Serum Amyloid P-Component) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptors) RN - 148591-49-5 (PTX3 protein) RN - 9007-41-4 (C-Reactive Protein) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) SB - IM MH - Alleles MH - C-Reactive Protein/analysis MH - CD40 Antigens/analysis MH - Carotid Artery, Common/*diagnostic imaging MH - Carotid Stenosis/*diagnostic imaging/genetics/immunology MH - Chemokine CCL2/analysis MH - Cyclooxygenase 2 MH - Female MH - Gene Expression MH - Genotype MH - Humans MH - Interleukin-6/analysis MH - Lipopolysaccharides/immunology MH - Macrophages/*immunology MH - Male MH - Membrane Glycoproteins/analysis/*genetics MH - Membrane Proteins MH - Middle Aged MH - Monocytes/*immunology MH - Polymorphism, Genetic/*genetics MH - Prospective Studies MH - Prostaglandin-Endoperoxide Synthases/analysis MH - Receptors, Cell Surface/analysis/*genetics MH - Serum Amyloid P-Component/analysis MH - Toll-Like Receptor 4 MH - Toll-Like Receptors MH - Ultrasonography EDAT- 2005/06/15 09:00 MHDA- 2005/07/20 09:00 CRDT- 2005/06/15 09:00 PHST- 2005/06/15 09:00 [pubmed] PHST- 2005/07/20 09:00 [medline] PHST- 2005/06/15 09:00 [entrez] AID - JIM1509 [pii] AID - 10.1111/j.1365-2796.2005.01509.x [doi] PST - ppublish SO - J Intern Med. 2005 Jul;258(1):21-7. doi: 10.1111/j.1365-2796.2005.01509.x. PMID- 15911702 OWN - NLM STAT- MEDLINE DCOM- 20060124 LR - 20101118 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 111 IP - 21 DP - 2005 May 31 TI - High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells. PG - 2805-11 AB - BACKGROUND: HDL is endowed with cardiovascular protective activities. In addition to its role in reverse cholesterol transport, HDL influences different functions of endothelial cells. In the present study, we investigated in endothelial cells the genes involved in inflammation modulated by HDL. METHODS AND RESULTS: Through cDNA array analysis, transforming growth factor (TGF)-beta2 appeared to be a gene responsive to HDL treatment in endothelial cells. Quantitative real-time polymerase chain reaction confirmed that HDL subfraction 3 selectively induces TGF-beta2 mRNA expression and protein release, whereas TGF-beta1 and TGF-beta3 were not affected. This effect was mainly PI3K/Akt dependent. Lysosphingolipids present in HDL such as sphingosine 1 phosphate and sphingosylphosphorylcholine mimicked the effects of the whole HDL. These results were confirmed in vivo in transgenic mice overexpressing human apolipoprotein (apo) A-I. Compared with apoA-I-knockout mice, phospho-Akt, phospho-ERK1/2, and TGF-beta2 expression was increased in the aorta of transgenic mice overexpressing human apoA-I. In addition, the expression of phospho-Smad2/3, the transcription factor activated by TGF-beta, is increased in transgenic mice compared with knockout mice. CONCLUSIONS: Because TGF-beta possesses antiinflammatory properties and stabilizes the plaque, the results of the present work suggest a novel target for the antiatherosclerotic effect of HDL. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. Danilo.Norata@unimi.it FAU - Callegari, Elisa AU - Callegari E FAU - Marchesi, Marta AU - Marchesi M FAU - Chiesa, Giulia AU - Chiesa G FAU - Eriksson, Per AU - Eriksson P FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050523 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Apolipoproteins E) RN - 0 (Lipoproteins, HDL) RN - 0 (Sphingolipids) RN - 0 (TGFB2 protein, human) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta2) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Oncogene Protein v-akt) SB - AIM SB - IM MH - Animals MH - Apolipoproteins E/genetics MH - Endothelial Cells/*metabolism MH - Endothelium, Vascular/*cytology MH - Gene Expression Profiling MH - Gene Expression Regulation/*drug effects MH - Humans MH - Inflammation/genetics MH - Lipoproteins, HDL/*pharmacology MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Oligonucleotide Array Sequence Analysis MH - Oncogene Protein v-akt/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Sphingolipids/pharmacology MH - Transforming Growth Factor beta/*genetics MH - Transforming Growth Factor beta2 EDAT- 2005/05/25 09:00 MHDA- 2006/01/25 09:00 CRDT- 2005/05/25 09:00 PHST- 2005/05/25 09:00 [pubmed] PHST- 2006/01/25 09:00 [medline] PHST- 2005/05/25 09:00 [entrez] AID - CIRCULATIONAHA.104.472886 [pii] AID - 10.1161/CIRCULATIONAHA.104.472886 [doi] PST - ppublish SO - Circulation. 2005 May 31;111(21):2805-11. doi: 10.1161/CIRCULATIONAHA.104.472886. Epub 2005 May 23. PMID- 15785302 OWN - NLM STAT- MEDLINE DCOM- 20050804 LR - 20190319 IS - 1741-8267 (Print) IS - 1741-8267 (Linking) VI - 12 IP - 2 DP - 2005 Apr TI - Cholesterol control in stroke prevention in Italy: a cross-sectional study in family practice. PG - 159-63 AB - BACKGROUND: Stroke represents worldwide the second and seventh cause of death and invalidity, respectively. Patients with ischaemic stroke or transitory ischaemic attack (TIA) are at high risk of recurrence, therefore requiring intensive treatment. Hypercholesterolaemia is a modifiable risk factor for stroke. The general practitioners attitude towards detection and treatment of dyslipidaemia among patients with stroke or TIA in Italy is unknown; we therefore aimed to address this issue taking advantage of the database of The Italian College of General Practitioners. METHODS: Prevalence of the monitored factors (lipid levels, statin prescription, and lipid level control with hypolipidaemic agents prescription) were analysed on a patient population of 465 061. RESULTS: A total of 2555 (49% women and 51% men) patients with a diagnosis of stroke and 2755 patients (52% women and 48% men) with a diagnosis of TIA were included in the study. Total plasma cholesterol (TC) was reported in more than 60% of the patients and low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) in less than half. Total plasma cholesterol and LDLc were controlled in 70.3 and 72.8% of the patients, respectively. The percentage of controlled patients decreased to 64% when both LDLc and TC were considered. Statins and fibrates were prescribed in a small proportion of patients (16.9 and 3.5%, respectively). An acceptable control of blood lipids was achieved in a majority of those patients (60.2%). However a relatively large number of patients (646) with high plasma lipids remained untreated. CONCLUSIONS: Monitoring and intervention strategies on plasma lipid levels in patients with a diagnosis of stroke or TIA need to be improved. FAU - Filippi, Alessandro AU - Filippi A AD - Italian College of General Practitioners, Florence, Italy. FAU - Tragni, Elena AU - Tragni E FAU - Bignamini, Angelo A AU - Bignamini AA FAU - Sessa, Emiliano AU - Sessa E FAU - Merlini, Giovanni AU - Merlini G FAU - Brignoli, Ovidio AU - Brignoli O FAU - Mazzaglia, Giampiero AU - Mazzaglia G FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Eur J Cardiovasc Prev Rehabil JT - European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology JID - 101192000 RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Age Distribution MH - Aged MH - Aged, 80 and over MH - Analysis of Variance MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Cross-Sectional Studies MH - Family Practice MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypercholesterolemia/drug therapy/*prevention & control MH - Incidence MH - Ischemic Attack, Transient/*epidemiology/*prevention & control MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Probability MH - Registries MH - Risk Assessment MH - Sex Distribution MH - Stroke/*epidemiology/*prevention & control MH - Survival Analysis EDAT- 2005/03/24 09:00 MHDA- 2005/08/05 09:00 CRDT- 2005/03/24 09:00 PHST- 2005/03/24 09:00 [pubmed] PHST- 2005/08/05 09:00 [medline] PHST- 2005/03/24 09:00 [entrez] AID - 00149831-200504000-00011 [pii] AID - 10.1097/01.hjr.0000161444.96302.cc [doi] PST - ppublish SO - Eur J Cardiovasc Prev Rehabil. 2005 Apr;12(2):159-63. doi: 10.1097/01.hjr.0000161444.96302.cc. PMID- 15902929 OWN - NLM STAT- MEDLINE DCOM- 20050804 LR - 20061115 IS - 1129-471X (Print) IS - 1129-471X (Linking) VI - 6 IP - 4 DP - 2005 Apr TI - The database of Italian general practitioners allows a reliable determination of the prevalence of myocardial infarction. PG - 311-4 AB - BACKGROUND: To plan preventive intervention after myocardial infarction (MI) the disease prevalence and the age and time from acute event of the index population should be known. METHODS: We identified all the living patients with MI coded diagnosis in the database of the Italian College of General Practitioners (Health Search Database-HSD). The years from the first acute MI were also determined. RESULTS: 3588 subjects with MI diagnosis were identified (2698 males and 888 females, for 2 gender not recorded). Based on the distribution of our population and on that reported by the Italian Institute of Statistics, stratified by gender and age (segments of 10 years), the estimated number of subjects with MI in Italy (age-standardized rates x 10000) was 309284 for men and 102343 for women. CONCLUSIONS: The prevalence of MI diagnosis in the HSD is very close to that obtained by other epidemiological methods. Querying the database can provide a simple and inexpensive way to estimate and monitor the prevalence of MI in Italy. FAU - Filippi, Alessandro AU - Filippi A AD - Italian College of General Practitioners, Florence, Italy. FAU - Vanuzzo, Diego AU - Vanuzzo D FAU - Bignamini, Angelo A AU - Bignamini AA FAU - Mazzaglia, Giampiero AU - Mazzaglia G FAU - Cricelli, Claudio AU - Cricelli C FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PL - Italy TA - Ital Heart J JT - Italian heart journal : official journal of the Italian Federation of Cardiology JID - 100909716 SB - IM MH - Adult MH - Age Distribution MH - Aged MH - *Databases, Factual MH - Family Practice/*standards/trends MH - Female MH - Humans MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Myocardial Infarction/diagnosis/*epidemiology MH - Physicians, Family MH - Prevalence MH - Registries MH - Reproducibility of Results MH - Risk Assessment MH - Sex Distribution MH - Survival Analysis EDAT- 2005/05/21 09:00 MHDA- 2005/08/05 09:00 CRDT- 2005/05/21 09:00 PHST- 2005/05/21 09:00 [pubmed] PHST- 2005/08/05 09:00 [medline] PHST- 2005/05/21 09:00 [entrez] PST - ppublish SO - Ital Heart J. 2005 Apr;6(4):311-4. PMID- 17315398 OWN - NLM STAT- MEDLINE DCOM- 20070316 LR - 20181113 IS - 1176-6344 (Print) IS - 1176-6344 (Linking) VI - 1 IP - 2 DP - 2005 TI - Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. PG - 119-29 AB - In addition to their role in reverse cholesterol transport, high-density lipoproteins (HDL) exert several beneficial effects, including the prevention and correction of endothelial dysfunction. HDL promote endothelium proliferation and diminish endothelial apoptosis; they play a key role in vasorelaxation by increasing the release of nitric oxide and prostacyclin through the induction of the expression and the activity of endothelial nitric oxide synthase and the coupling of cyclooxygenase 2 and prostacyclin synthase. In addition, HDL affect coagulation, fibrinolysis, platelet adhesion, adhesion molecules, and protease expression, and they exert antioxidant activity. These effects are achieved at the gene expression level and are dependent on the activation of several intracellular signaling pathways, including PI3K/Akt, ERK1/2, PKC, and p38MAPK. The complexity of the signaling pathways modulated by HDL reflects the different effects of the components of this class of lipoproteins such as apolipoproteins or lipids on endothelial cell gene expression and the subsequent modulation of endothelial function observed. The in vivo relevance of these findings to endothelial recovery during physiological or pathological conditions remains to be addressed; nevertheless, the results of clinical studies with synthetic HDL, ApoA-I mimetics, and drugs that are becoming available that selectively affect HDL plasma levels and biological functions support the importance of the correction of endothelial function by HDL. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Italy. danilo.norata@unimi.it FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - New Zealand TA - Vasc Health Risk Manag JT - Vascular health and risk management JID - 101273479 RN - 0 (Lipoproteins, HDL) SB - IM MH - Animals MH - Blood Coagulation MH - Cardiovascular Diseases/blood/*metabolism/physiopathology MH - Cell Movement MH - Cell Proliferation MH - Endothelium, Vascular/*metabolism/physiopathology MH - Fibrinolysis MH - Humans MH - Inflammation/blood/*metabolism/physiopathology MH - Lipoproteins, HDL/*metabolism MH - Neovascularization, Pathologic/metabolism MH - Platelet Adhesiveness MH - Signal Transduction MH - Vasodilation RF - 98 PMC - PMC1993938 EDAT- 2007/02/24 09:00 MHDA- 2007/03/17 09:00 CRDT- 2007/02/24 09:00 PHST- 2007/02/24 09:00 [pubmed] PHST- 2007/03/17 09:00 [medline] PHST- 2007/02/24 09:00 [entrez] PST - ppublish SO - Vasc Health Risk Manag. 2005;1(2):119-29. PMID- 15384983 OWN - NLM STAT- MEDLINE DCOM- 20041124 LR - 20091119 IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 127 IP - 1 DP - 2004 Oct TI - Oxidised-HDL3 induces the expression of PAI-1 in human endothelial cells. Role of p38MAPK activation and mRNA stabilization. PG - 97-104 AB - Modified lipoproteins have been suggested to modulate endothelial expression of plasminogen activator inhibitor-1 (PAI-1). As oxidized high-density lipoprotein (Ox-HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of Ox-HDL3 on the expression of PAI-1. Ox-HDL3 but not native HDL3, increased PAI-1 mRNA expression in endothelial cells. Furthermore, PAI-1 antigen expression and activity increased in the supernatant of cells incubated with Ox-HDL3. The intracellular pathways involved in this effect were investigated. Ox-HDL3 activated both extracellular signal-regulated kinases (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). Moreover, incubation with specific inhibitors of these kinases showed that p38MAPK was mainly involved in the Ox-HDL3-dependent PAI-1 induction. Transient transfection experiments suggested that none of the response elements in the proximal promoter (-804 to 17) were involved in Ox-HDL3-mediated PAI-1 expression. mRNA stability experiments showed that Ox-HDL3 increased the PAI-1 mRNA half-life. In summary, Ox-HDL3 induced PAI-1 mRNA expression and antigen release through a molecular mechanism involving MAPK activation and mRNA stabilization. Thus, oxidative modification converts HDL to a prothrombotic lipoprotein species. CI - Copyright 2004 Blackwell Publishing Ltd FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. danilo.norata@unimi.it FAU - Banfi, Cristina AU - Banfi C FAU - Pirillo, Angela AU - Pirillo A FAU - Tremoli, Elena AU - Tremoli E FAU - Hamsten, Anders AU - Hamsten A FAU - Catapano, Alberico L AU - Catapano AL FAU - Eriksson, Per AU - Eriksson P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 0 (RNA, Messenger) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Endothelial Cells/*drug effects/metabolism MH - Endothelium, Vascular/drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Lipoproteins, HDL/*pharmacology MH - Lipoproteins, HDL3 MH - Oxidation-Reduction MH - Plasminogen Activator Inhibitor 1/*biosynthesis/genetics MH - Polymerase Chain Reaction/methods MH - RNA, Messenger/genetics MH - p38 Mitogen-Activated Protein Kinases/*physiology EDAT- 2004/09/24 05:00 MHDA- 2004/12/16 09:00 CRDT- 2004/09/24 05:00 PHST- 2004/09/24 05:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/09/24 05:00 [entrez] AID - 10.1111/j.1365-2141.2004.05163.x [doi] AID - BJH5163 [pii] PST - ppublish SO - Br J Haematol. 2004 Oct;127(1):97-104. doi: 10.1111/j.1365-2141.2004.05163.x. PMID- 15615349 OWN - NLM STAT- MEDLINE DCOM- 20050131 LR - 20131121 IS - 1129-4728 (Print) IS - 1129-4728 (Linking) VI - 5 IP - 10 DP - 2004 Oct TI - [Intestinal cholesterol absorption: a pharmacological target for lowering of plasma cholesterol]. PG - 779-84 AB - A number of clinical studies clearly demonstrate the efficacy of hypocholesterolemic treatment in reducing incident cardiovascular events. The benefit appears to be proportional to the reduction of LDL cholesterol. Recent guidelines suggest an even more stringent target of 70 mg/dl for LDL cholesterol in high-risk subjects. Statins represent a very effective treatment of hypercholesterolemia, and the co-administration of drugs with complementary mechanisms of action, may represent an additional pharmacological tool in clinical practice to achieve the suggested targets for LDL lowering. In this short review we address the most recent discoveries in the physiological pathways of cholesterol absorption and identify the concept of dual inhibition as a therapeutic paradigm that may help in reaching the LDL cholesterol targets in clinical practice. FAU - Catapano, Alberico L AU - Catapano AL AD - Dipartimento di Scienze Farmacologiche, Centro per lo Studio dell'Aterosclerosi, Universita degli Studi, Milano. alberico.catapano@unimi.it FAU - Catapano, Luca AU - Catapano L FAU - Fellin, Renato AU - Fellin R LA - ita PT - Comparative Study PT - English Abstract PT - Journal Article PT - Review TT - L'assorbimento intestinale del colesterolo: un bersaglio farmacologico per il controllo dei livelli di colesterolo plasmatici. PL - Italy TA - Ital Heart J Suppl JT - Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology JID - 101223651 RN - 0 (Cholesterol, LDL) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoproteins) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cardiovascular Diseases/etiology MH - Cholesterol/biosynthesis/*metabolism MH - Cholesterol, LDL/*blood MH - Diet MH - Humans MH - Hypercholesterolemia/complications/*drug therapy/physiopathology MH - Hypolipidemic Agents/*therapeutic use MH - *Intestinal Absorption MH - Lipoproteins/metabolism MH - Practice Guidelines as Topic MH - Randomized Controlled Trials as Topic MH - Risk Factors RF - 23 EDAT- 2004/12/24 09:00 MHDA- 2005/02/03 09:00 CRDT- 2004/12/24 09:00 PHST- 2004/12/24 09:00 [pubmed] PHST- 2005/02/03 09:00 [medline] PHST- 2004/12/24 09:00 [entrez] PST - ppublish SO - Ital Heart J Suppl. 2004 Oct;5(10):779-84. PMID- 15289885 OWN - NLM STAT- MEDLINE DCOM- 20050309 LR - 20180815 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 14 IP - 3 DP - 2004 Sep TI - Native LDL and oxidized LDL modulate cyclooxygenase-2 expression in HUVECs through a p38-MAPK, NF-kappaB, CRE dependent pathway and affect PGE2 synthesis. PG - 353-9 AB - Native low density lipoproteins (n-LDL) and oxidized low density lipoproteins (Ox-LDL) play a central role in atherogenesis and possess a wide variety of biological properties. We investigated whether n-LDL or Ox-LDL modulate cyclooxygenase-1 and -2 (Cox-1 and Cox-2) expression and prostaglandins release in human endothelial cells via an MAPK-dependent pathway. HUVECs were incubated in the presence of n-LDL or Ox-LDL (30 micro g/ml for both) for 2-15 h. Real-time PCR, western blotting and immunocytochemistry were used to investigate Cox-1 and Cox-2 expression. N-LDL and Ox-LDL induced Cox-2 expression in a time- and dose-dependent manner. The Cox-2 protein was strongly induced 2 h after exposure to n-LDL or Ox-LDL, the induction was maximal after 4 h and sustained for at least 8 h. The effect was specific for Cox-2, as Cox-1 expression was not modulated either by n-LDL or by Ox-LDL. The induction of Cox-2 expression was mainly dependent on the activation of p38 MAPK. Transient transfection analysis using a Cox-2 promoter showed that n-LDL and Ox-LDL exert their effects at the transcriptional level via NF-kappaB and CREB activation. N-LDL and Ox-LDL increased PGE2 release in a Cox-2-dependent manner while TXA2 and PGI2 release were not affected either by n-LDL or Ox-LDL. The finding that n-LDL and Ox-LDL induces Cox-2 in human endothelial cells through a p38 MAPK, NF-kappaB, CREB dependent pathway thus modulating PGE2 release, suggests a new mechanism by which these lipoproteins induce endothelial dysfunction, sustaining inflammatory processes in the arterial wall. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Italy. alberico.catapano@unimi.it FAU - Pirillo, A AU - Pirillo A FAU - Pellegatta, F AU - Pellegatta F FAU - Inoue, H AU - Inoue H FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 0 (Cyclooxygenase Inhibitors) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Imidazoles) RN - 0 (Lipoproteins, LDL) RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 0 (Pyridines) RN - 57576-52-0 (Thromboxane A2) RN - DCR9Z582X0 (Epoprostenol) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - K7Q1JQR04M (Dinoprostone) RN - OU13V1EYWQ (SB 203580) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) RN - XXE1CET956 (Indomethacin) SB - IM MH - Cells, Cultured MH - Cyclooxygenase 2 MH - Cyclooxygenase 2 Inhibitors MH - Cyclooxygenase Inhibitors/pharmacology MH - Dinoprostone/*biosynthesis MH - Dose-Response Relationship, Drug MH - Enzyme Induction MH - Enzyme Inhibitors/pharmacology MH - Epoprostenol/biosynthesis MH - Flavonoids/pharmacology MH - Gene Expression Regulation, Enzymologic/*drug effects MH - Humans MH - Imidazoles/pharmacology MH - Immunoassay MH - Immunoblotting MH - Immunohistochemistry MH - Indomethacin/pharmacology MH - Lipoproteins, LDL/*pharmacology MH - Membrane Proteins MH - NF-kappa B/*metabolism MH - Oxidation-Reduction MH - Prostaglandin-Endoperoxide Synthases/*metabolism MH - Pyridines/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Thromboxane A2/biosynthesis MH - Time Factors MH - Umbilical Veins/cytology MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism EDAT- 2004/08/04 05:00 MHDA- 2005/03/10 09:00 CRDT- 2004/08/04 05:00 PHST- 2004/08/04 05:00 [pubmed] PHST- 2005/03/10 09:00 [medline] PHST- 2004/08/04 05:00 [entrez] PST - ppublish SO - Int J Mol Med. 2004 Sep;14(3):353-9. PMID- 15181082 OWN - NLM STAT- MEDLINE DCOM- 20040719 LR - 20061115 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 89 IP - 6 DP - 2004 Jun TI - Lipoprotein remnants and endothelial dysfunction in the postprandial phase. PG - 2946-50 AB - The objective of this work was to study whether changes in remnant lipoprotein (RLP) plasma levels during the postprandial phase relate to alterations of the endothelial function. Fasted patients (15 moderately dyslipidemic men) were given an oral fat load (OFL), and blood samples were collected before the OFL ingestion (T0) and 2, 4, 6, and 8 h (T2, T4, T6, T8) thereafter. Endothelial function, determined as flow-mediated dilatation (FMD) of the brachial artery, was assessed at the same time points. Triglyceridemia peaked between T4 (5.48 +/- 0.64 mmol/liter) and T6 (5.34 +/- 0.89 mmol/liter) and decreased at 8 h (4.36 +/- 0.87 mmol/liter) after the OFL. FMD decreased significantly 6 h after the OFL consumption (from 16.03 +/- 1.32% to 11.53 +/- 1.42%, P < 0.01). Cholesterol in RLPs increased steadily up to 6 h and decreased at 8 h (T0 0.53 +/- 0.10, T6 0.81 +/- 0.11, T8 0.73 +/- 0.13 mmol/liter). Fasting levels of triglycerides and cholesterol-RLPs (C-RLPs) correlated significantly with FMD at baseline. The decrease in endothelial function at 6 h also significantly correlated with the area under the curve of triglycerides (R = 0.53, P = 0.04). Postprandial C-RLPs (area under the curve), however, showed the best correlation with the decrease of FMD (R = 0.63, P = 0.012). The correlation persisted in a multivariate analysis. We concluded that C-RLPs contribute significantly to the endothelial dysfunction occurring during the postprandial lipemia. FAU - Maggi, Franco Maria AU - Maggi FM AD - Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy. FAU - Raselli, Sara AU - Raselli S FAU - Grigore, Liliana AU - Grigore L FAU - Redaelli, Laura AU - Redaelli L FAU - Fantappie, Simona AU - Fantappie S FAU - Catapano, Alberico Luigi AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Dietary Fats) RN - 0 (Lipoproteins) RN - 0 (Triglycerides) SB - AIM SB - IM MH - Adult MH - Aged MH - Arteriosclerosis/metabolism MH - Dietary Fats/pharmacokinetics MH - Endothelium, Vascular/*metabolism MH - Fasting MH - Humans MH - Hyperlipidemias/*metabolism MH - Lipoproteins/*blood MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Postprandial Period MH - Triglycerides/blood EDAT- 2004/06/08 05:00 MHDA- 2004/07/20 05:00 CRDT- 2004/06/08 05:00 PHST- 2004/06/08 05:00 [pubmed] PHST- 2004/07/20 05:00 [medline] PHST- 2004/06/08 05:00 [entrez] AID - 10.1210/jc.2003-031977 [doi] AID - 89/6/2946 [pii] PST - ppublish SO - J Clin Endocrinol Metab. 2004 Jun;89(6):2946-50. doi: 10.1210/jc.2003-031977. PMID- 15001457 OWN - NLM STAT- MEDLINE DCOM- 20041014 LR - 20181130 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 24 IP - 5 DP - 2004 May TI - HDL3 induces cyclooxygenase-2 expression and prostacyclin release in human endothelial cells via a p38 MAPK/CRE-dependent pathway: effects on COX-2/PGI-synthase coupling. PG - 871-7 AB - OBJECTIVE: In endothelial cells, cyclooxygenase-1 (COX-1) and COX-2 both contribute to prostacyclin production. Recent findings suggest that COX-2 contributes significantly to systemic prostacyclin synthesis in humans; whether COX-2 inhibition is related to an increased cardiovascular risk is undergoing debate. HDLs have been shown to increase prostacyclin synthesis, thus in the present study we investigated the molecular mechanisms involved in this effect in endothelial cells. METHODS AND RESULTS: HDL3 (30 microg/mL) induced COX-2 expression in a time- and dose-dependent manner. COX-2 was found mainly in the perinuclear area where it co-localizes with PGI synthase. Transient transfection experiments showed that CRE is required for HDL-induced COX-2 transcription, and we demonstrated that p38 MAPK activation by HDL3 is involved in COX-2 mRNA transcription and stabilization. As a consequence of COX-2-induction by HDL3 prostacyclin production increased, incubation with a COX-2 selective inhibitor blocked this effect. Moreover, HDL3 increased caveolin-1 phosphorylation, thus promoting PGI-synthase shuttling from the membrane to the perinuclear area. CONCLUSIONS: We conclude that in endothelial cells, HDL modulates COX-2/PGI-S activity via both p38 MAPK-dependent COX-2 mRNA stability and transcription and both caveolin-1-dependent PGI-synthase shuttling and COX-2 coupling. The understanding of these mechanisms may provide new insights into the antiatherogenic role of HDL. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Italy. FAU - Callegari, E AU - Callegari E FAU - Inoue, H AU - Inoue H FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article DEP - 20040304 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (CAV1 protein, human) RN - 0 (CREB1 protein, human) RN - 0 (Caveolin 1) RN - 0 (Caveolins) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (I-kappa B Proteins) RN - 0 (Isoenzymes) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 0 (Membrane Proteins) RN - 0 (NFKBIA protein, human) RN - 0 (Prostaglandins I) RN - 0 (Transcription Factors) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - EC 5.3.99.4 (prostacyclin synthetase) SB - IM MH - Caveolin 1 MH - Caveolins/physiology MH - Cells, Cultured/enzymology/metabolism MH - Cyclic AMP Response Element-Binding Protein/physiology MH - Cyclooxygenase 2 MH - Cytochrome P-450 Enzyme System/metabolism MH - Endothelial Cells/*enzymology/metabolism MH - Endothelium, Vascular/*cytology MH - Enzyme Induction MH - Humans MH - I-kappa B Proteins/physiology MH - Image Processing, Computer-Assisted MH - Intramolecular Oxidoreductases/metabolism MH - Isoenzymes/*biosynthesis/genetics MH - Lipoproteins, HDL/*physiology MH - Lipoproteins, HDL3 MH - MAP Kinase Signaling System MH - Membrane Proteins MH - NF-KappaB Inhibitor alpha MH - Phosphorylation MH - Prostaglandin-Endoperoxide Synthases/*biosynthesis/genetics MH - Prostaglandins I/*metabolism MH - Protein Processing, Post-Translational MH - Reverse Transcriptase Polymerase Chain Reaction MH - Subcellular Fractions/chemistry MH - Transcription Factors/physiology MH - Transfection MH - Umbilical Veins/cytology EDAT- 2004/03/06 05:00 MHDA- 2004/10/16 09:00 CRDT- 2004/03/06 05:00 PHST- 2004/03/06 05:00 [pubmed] PHST- 2004/10/16 09:00 [medline] PHST- 2004/03/06 05:00 [entrez] AID - 10.1161/01.ATV.zhq0504.1403 [doi] AID - 01.ATV.zhq0504.1403 [pii] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2004 May;24(5):871-7. doi: 10.1161/01.ATV.zhq0504.1403. Epub 2004 Mar 4. PMID- 15053163 OWN - NLM STAT- MEDLINE DCOM- 20040629 LR - 20180529 IS - 0939-4753 (Print) IS - 0939-4753 (Linking) VI - 14 IP - 1 DP - 2004 Feb TI - Lipid lowering activity of drugs affecting cholesterol absorption. PG - 42-51 AB - AIM: Dietary cholesterol absorption, endogenous cholesterol synthesis and biliary cholesterol excretion regulate whole body cholesterol balance as a result of biotransformation into bile acids or direct cholesterol excretion. Recent studies have significantly advanced our understanding of intestinal sterol absorption at molecular level. This review concentrates on two major issues: the mechanisms of sterol absorption, and the currently available or experimental drugs that affect this pathway. DATA SYNTHESIS: Nuclear hormone receptors, such as the liver X, farnesoid X and retinoid X receptors, regulate the absorption of dietary sterols by modulating the transcription of several genes involved in cholesterol metabolism, The ABC proteins transport dietary cholesterol from enterocytes back to the intestinal lumen, thus limiting the amount of absorbed cholesterol. By means of the same mechanism, ABC transporters also provide an efficient barrier against the absorption of plant sterols. Phytosterols, bile acid sequestrants, ezetimibe and ACAT inhibitors are possible means of affecting these pathways. CONCLUSION: In addition to providing an insight into the molecular mechanisms of sterol absorption, these recent findings may lead to new therapeutic options for the treatment of hypercholesterolemia. This is particularly true in the case of patients at high risk of coronary artery disease requiring aggressive lipid-lowering therapy combining a statin with drugs affecting cholesterol absorption in order to ensure the optimal management of dyslipidemia. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milano, Milano, Italy. FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Anticholesteremic Agents) RN - 0 (Azetidines) RN - 0 (Cholesterol, Dietary) RN - 0 (Sterols) RN - 97C5T2UQ7J (Cholesterol) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Anticholesteremic Agents/pharmacology/*therapeutic use MH - Azetidines/pharmacology/therapeutic use MH - Cholesterol/biosynthesis/*metabolism MH - Cholesterol, Dietary/*pharmacokinetics MH - Ezetimibe MH - Humans MH - Hypercholesterolemia/*prevention & control MH - Intestinal Absorption/*drug effects MH - Molecular Biology MH - Sterols/*pharmacokinetics RF - 54 EDAT- 2004/04/01 05:00 MHDA- 2004/06/30 05:00 CRDT- 2004/04/01 05:00 PHST- 2004/04/01 05:00 [pubmed] PHST- 2004/06/30 05:00 [medline] PHST- 2004/04/01 05:00 [entrez] AID - S0939-4753(04)80046-2 [pii] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2004 Feb;14(1):42-51. PMID- 14996435 OWN - NLM STAT- MEDLINE DCOM- 20041025 LR - 20161124 IS - 0945-053X (Print) IS - 0945-053X (Linking) VI - 22 IP - 7 DP - 2004 Jan TI - High-density lipoprotein subfraction 3 decreases ADAMTS-1 expression induced by lipopolysaccharide and tumor necrosis factor-alpha in human endothelial cells. PG - 557-60 AB - Endothelial expression of matrix metalloproteinases has been implicated in angiogenesis and endothelial cell proliferation. Recently, it has been shown that high-density lipoproteins (HDLs) promote angiogenesis. In the present study, we investigated the effects of native HDLs on the expression of several proteases and their inhibitors in human umbilical vein endothelial cells. We show that ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif) was potently induced by incubation with lipopolysaccharide or tumor necrosis factor-alpha and that the expression was significantly reduced in the presence of HDL subfraction 3. Since ADAMTS-1 has recently been shown to inhibit endothelial cell proliferation, the result of the present work may represent a new mechanism by which HDL could have a positive effect on endothelial cell and vascular wall function. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Bjork, Hanna AU - Bjork H FAU - Hamsten, Anders AU - Hamsten A FAU - Catapano, Alberico L AU - Catapano AL FAU - Eriksson, Per AU - Eriksson P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Matrix Biol JT - Matrix biology : journal of the International Society for Matrix Biology JID - 9432592 RN - 0 (Disintegrins) RN - 0 (Lipopolysaccharides) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.- (Metalloproteases) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.- (ADAMTS1 Protein) RN - EC 3.4.24.- (ADAMTS1 protein, human) RN - EC 3.4.24.- (Metalloendopeptidases) SB - IM MH - ADAM Proteins MH - ADAMTS1 Protein MH - Cells, Cultured MH - Disintegrins/*antagonists & inhibitors/genetics MH - Endothelial Cells/*metabolism MH - Gene Expression/drug effects MH - Humans MH - Lipopolysaccharides/*pharmacology MH - Lipoproteins, HDL/pharmacology/*physiology MH - Lipoproteins, HDL3 MH - Metalloendopeptidases/*antagonists & inhibitors/genetics MH - Metalloproteases/metabolism MH - RNA, Messenger/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2004/03/05 05:00 MHDA- 2004/10/27 09:00 CRDT- 2004/03/05 05:00 PHST- 2003/09/04 00:00 [received] PHST- 2003/11/04 00:00 [revised] PHST- 2003/11/11 00:00 [accepted] PHST- 2004/03/05 05:00 [pubmed] PHST- 2004/10/27 09:00 [medline] PHST- 2004/03/05 05:00 [entrez] AID - 10.1016/j.matbio.2003.11.003 [doi] AID - S0945053X03001069 [pii] PST - ppublish SO - Matrix Biol. 2004 Jan;22(7):557-60. doi: 10.1016/j.matbio.2003.11.003. PMID- 14983746 OWN - NLM STAT- MEDLINE DCOM- 20040520 LR - 20061115 IS - 1129-471X (Print) IS - 1129-471X (Linking) VI - 4 Suppl 7 DP - 2003 Dec TI - [Achievement of the therapeutic goals for dyslipidemia in clinical practice: results of a survey among general practice physicians from Lombardy]. PG - 47S-57S AB - BACKGROUND: Currently available guidelines suggest that hypolipidemic drugs should be used in subjects at high risk for coronary heart disease (CHD). Very often, however, physicians fail to comply with the targets (total or LDL cholesterol) that are proposed by the Consensus Panels. The aim of this survey was to evaluate the efficacy of a hypocholesterolemic treatment in achieving the therapeutic target according to Adult Treatment Panel II guidelines in a sample of general practitioners from Lombardy, a region of northern Italy. METHODS: Eighty-five general practitioners reported in a standardized manner data on the presence of major and minor coronary risk factors from at least 15 patients from their database for a total of 1275 patients. Treatment targets for LDL cholesterol were 100 mg/dl in patients with existing cardiovascular disease (class I), 130 mg/dl for patients with > or = 2 CHD risk factors (class II), and 160 mg/dl for the others (class III). Results on the efficacy of the therapy were divided into the following categories: 1) to target, 2) failure to reach the target by < or = 30 mg/dl, 3) failure to reach the target by > 30 mg/dl. Data were analyzed by means of the CSS statistical software. RESULTS: Overall 58.2% of the patients were males and the average age of the population was 59.2 +/- 10.1 years; 20.4% were diabetics, 34.5% smokers, 48.8% hypertensives, 16.9% had a previous myocardial infarction, 14.9% were suffering of stable angina, and 8.1% had undergone coronary artery bypass grafting and/or coronary angioplasty. Moreover 33.9% had a positive family history for CHD. Class I patients were 31.7% of the population, class II 52.9%, and class III 15.4%. Plasma lipid levels before treatment were on average 294 +/- 37 mg/dl for total cholesterol, 211 +/- 37 mg/dl for LDL cholesterol, 45 +/- 16 mg/dl for HDL cholesterol, and 195 +/- 104 mg/dl for plasma triglycerides. Of the patients 78.8% received dietary counseling, while 94.7% received hypolipidemic treatment (89.9% were only on statins). The average post-treatment value for total cholesterol was 225 +/- 33 mg/dl (-23%), LDL cholesterol 145 +/- 34 mg/dl (-31%), HDL cholesterol 50 +/- 15 (+15%), and plasma triglycerides 151 +/- 55 (-17%). When patients were stratified according to their LDL cholesterol target, 29.9% were on target, 34.0% missed it by < or = 30 mg/dl, and 36.1% by > 30 mg/dl. In class I only 14.9% achieved the target, in class II 31.2%, in class III 61.8%. CONCLUSIONS: These data show that general practitioners do not aim at an aggressive lipid lowering in patients at high risk, perhaps because of the limited knowledge of the need for modulating treatment according to the global CHD risk. FAU - Tragni, Elena AU - Tragni E AD - Servizio di Epidemiologia e Farmacologia Preventiva (SEFAP), Dipartimento di Scienze Farmacologiche, Universita degli Studi, Via Balzaretti, 9 20133 Milano. elena.tragni@unimi.it FAU - Catapano, Alberico L AU - Catapano AL FAU - Bertelli, Alessandra AU - Bertelli A FAU - Poli, Andrea AU - Poli A LA - ita PT - English Abstract PT - Journal Article TT - Raggiungimento degli obiettivi terapeutici per le dislipidemie nella pratica clinica: risultati di un'indagine tra i medici di medicina generale della Lombardia. PL - Italy TA - Ital Heart J JT - Italian heart journal : official journal of the Italian Federation of Cardiology JID - 100909716 SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Family Practice MH - Female MH - Humans MH - Hypercholesterolemia/*drug therapy MH - Italy MH - Male MH - Middle Aged EDAT- 2004/02/27 05:00 MHDA- 2004/05/21 05:00 CRDT- 2004/02/27 05:00 PHST- 2004/02/27 05:00 [pubmed] PHST- 2004/05/21 05:00 [medline] PHST- 2004/02/27 05:00 [entrez] PST - ppublish SO - Ital Heart J. 2003 Dec;4 Suppl 7:47S-57S. PMID- 14983744 OWN - NLM STAT- MEDLINE DCOM- 20040520 LR - 20151119 IS - 1129-471X (Print) IS - 1129-471X (Linking) VI - 4 Suppl 7 DP - 2003 Dec TI - [Rosuvastatin: pharmacologic features]. PG - 22S-32S AB - The development of more active and safe new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) will increase the armamentarium of therapeutic tools available to the physicians for antiatherosclerotic therapies. Rosuvastatin presents a promising pharmacological profile: high affinity for the enzyme, a relative high hydrophilicity, selective hepatic uptake and activity, minimal cytochrome P450-mediated metabolism. Clinically the drug displays the highest lipid-lowering efficacy in the class with a safety profile similar to the other statins. Drug interaction potential is reduced. Rosuvastatin effectively decreases triglycerides, triglyceride-rich lipoproteins, non-HDL cholesterol, and increases HDL cholesterol. All together these properties will favor the achievement of therapeutic goals in the treated patients. FAU - Bernini, Franco AU - Bernini F AD - Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Universita degli Studi, Campus Universiario, 43100 Parma. fbernini@unipr.it FAU - Catapano, Alberico L AU - Catapano AL LA - ita PT - English Abstract PT - Journal Article PT - Review TT - La rosuvastatina: aspetti farmacologici. PL - Italy TA - Ital Heart J JT - Italian heart journal : official journal of the Italian Federation of Cardiology JID - 100909716 RN - 0 (Fluorobenzenes) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Hypolipidemic Agents) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 0 (Triglycerides) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Arteriosclerosis/blood/prevention & control MH - Biotransformation MH - Cholesterol/blood MH - Drug Interactions MH - Fluorobenzenes/chemistry/*pharmacology/therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry/*pharmacology/therapeutic use MH - Hypercholesterolemia/prevention & control MH - Hyperlipidemias/blood/prevention & control MH - Hypolipidemic Agents/pharmacology MH - Inflammation/prevention & control MH - Pyrimidines/chemistry/*pharmacology/therapeutic use MH - Rosuvastatin Calcium MH - Sulfonamides/chemistry/*pharmacology/therapeutic use MH - Triglycerides/blood RF - 33 EDAT- 2004/02/27 05:00 MHDA- 2004/05/21 05:00 CRDT- 2004/02/27 05:00 PHST- 2004/02/27 05:00 [pubmed] PHST- 2004/05/21 05:00 [medline] PHST- 2004/02/27 05:00 [entrez] PST - ppublish SO - Ital Heart J. 2003 Dec;4 Suppl 7:22S-32S. PMID- 12829188 OWN - NLM STAT- MEDLINE DCOM- 20031014 LR - 20091119 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 59 IP - 1 DP - 2003 Jul 1 TI - Gene expression and intracellular pathways involved in endothelial dysfunction induced by VLDL and oxidised VLDL. PG - 169-80 AB - OBJECTIVES: The molecular mechanisms underlying the relationship between elevated plasma concentrations of triglyceride-rich lipoproteins and coronary artery disease remain uncertain. In the present work, we investigated the gene expression pattern and intracellular pathways in human endothelial cells incubated with very low density lipoproteins (VLDL). Moreover, as VLDL can enter the arterial wall and undergo oxidative modification, we compared the VLDL-induced expression pattern with the one of oxidised VLDL (Ox-VLDL). METHODS: Total RNA from endothelial cells incubated with 75 microg/ml VLDL or Ox-VLDL and total RNA from endothelial cells under basal conditions were hybridised to identical microarrays containing 8411 genes. Seven clusters of expression profiles were identified. This pattern was validated by quantitative real-time PCR of selected genes. The intracellular pathway involved in VLDL or Ox-VLDL mediated endothelial responses were also investigated. RESULTS AND CONCLUSION: VLDL predominantly activated the ERK1/2 pathway while P38 MAPK was the main target of Ox-VLDL. CREB and NF-kappa B were activated by both VLDL and Ox-VLDL. Real-time PCR demonstrated that VLDL induced matrix metalloproteinase-2 (5.47+/-1.74 fold), CD38 (2.38+/-0.23) and transforming growth factor-alpha (2.51+/-0.30) expression. Ox-VLDL was found to induce interleukin-15 (2.10+/-0.48) and macrophage migration inhibitory factor (3.19+/-0.07) expression. In addition, several genes implicated in endothelial cell activation and damage/proliferation were identified by the array analysis. Ox-VLDL was found to promote the generation of reactive oxygen species and exert a cytotoxic effect, while VLDL lacks these effects. These findings confirm the involvement of VLDL and Ox-VLDL in endothelial dysfunction and suggest new genes and molecular mechanisms involved in these actions. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Pirillo, A AU - Pirillo A FAU - Callegari, E AU - Callegari E FAU - Hamsten, A AU - Hamsten A FAU - Catapano, A L AU - Catapano AL FAU - Eriksson, P AU - Eriksson P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Interleukin-15) RN - 0 (Lipoproteins, VLDL) RN - 0 (Macrophage Migration-Inhibitory Factors) RN - 0 (NF-kappa B) RN - 0 (oxidized very low density lipoprotein) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cell Death MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Endothelium, Vascular/*metabolism MH - Enzyme Activation MH - *Gene Expression Profiling MH - Humans MH - Interleukin-15/genetics MH - Lipoproteins, VLDL/metabolism/*pharmacology MH - Macrophage Migration-Inhibitory Factors/genetics MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - *Oligonucleotide Array Sequence Analysis MH - Oxidation-Reduction MH - Oxidative Stress MH - Reverse Transcriptase Polymerase Chain Reaction MH - p38 Mitogen-Activated Protein Kinases EDAT- 2003/06/28 05:00 MHDA- 2003/10/15 05:00 CRDT- 2003/06/28 05:00 PHST- 2003/06/28 05:00 [pubmed] PHST- 2003/10/15 05:00 [medline] PHST- 2003/06/28 05:00 [entrez] AID - S0008636303003353 [pii] PST - ppublish SO - Cardiovasc Res. 2003 Jul 1;59(1):169-80. PMID- 12792812 OWN - NLM STAT- MEDLINE DCOM- 20040204 LR - 20061115 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 12 IP - 1 DP - 2003 Jul TI - Effects of HDL3 on the expression of matrix-degrading proteases in human endothelial cells. PG - 73-8 AB - Modified lipoproteins have been suggested to modulate the expression of matrix-degrading proteases in the vascular wall. Since oxidized high density lipoprotein (HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the role of native and oxidized HDL3 on the expression of 35 proteases and their inhibitors in human endothelial cells using microarray analysis. Matrix metalloproteinase (MMP)-1, -2, -10, -13 and -14, tissue inhibitor of MMP (TIMP)-1, -2 and -3, cathepsin B and D, and cystatin C were expressed under basal conditions, of which MMP-10 and cystatin C expression have not been described before in endothelial cells. Native HDL3 increased MMP-1 and MMP-14 expression and decreased MMP-13 expression, whereas oxidized HDL3 increased PAI-1 and MMP-1 expression. The expression pattern was confirmed by quantitative real-time PCR. In summary, a large repertoire of matrix-degrading proteases is expressed in endothelial cells, an expression that can be modulated by native and oxidized HDL3. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, Milan, Italy. FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Hamsten, Anders AU - Hamsten A FAU - Catapano, Alberico L AU - Catapano AL FAU - Eriksson, Per AU - Eriksson P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - EC 3.4.- (Endopeptidases) SB - IM MH - Endopeptidases/biosynthesis/*genetics MH - Endothelium, Vascular/*metabolism MH - Extracellular Matrix/*metabolism MH - Humans MH - Lipoproteins, HDL/*metabolism MH - Lipoproteins, HDL3 MH - Oligonucleotide Array Sequence Analysis MH - Polymerase Chain Reaction EDAT- 2003/06/07 05:00 MHDA- 2004/02/05 05:00 CRDT- 2003/06/07 05:00 PHST- 2003/06/07 05:00 [pubmed] PHST- 2004/02/05 05:00 [medline] PHST- 2003/06/07 05:00 [entrez] PST - ppublish SO - Int J Mol Med. 2003 Jul;12(1):73-8. PMID- 12783430 OWN - NLM STAT- MEDLINE DCOM- 20030709 LR - 20081121 IS - 0364-5134 (Print) IS - 0364-5134 (Linking) VI - 53 IP - 6 DP - 2003 Jun TI - Apolipoprotein C-II deficiency presenting as a lipid encephalopathy in infancy. PG - 807-10 AB - An infant presented with massive hyperchylomicronemia and a severe encephalopathy. MRI showed marked lipid deposition throughout the brain. Despite the normalization of the biochemistry, there was little clinical improvement, and at 18 months of age she has severe developmental delay, a strikingly abnormal MRI. Apolipoprotein C-II, the lipoprotein on chylomicrons responsible for the activation of lipoprotein lipase, was not detectable in blood. Analysis of the APO C-II gene revealed a novel homozygous point mutation, 1118C-->A. Subsequently, another sibling has been born with the same homozygous mutation and similar biochemistry but, perhaps because of early treatment, a normal neurological outcome. FAU - Wilson, Callum J AU - Wilson CJ AD - Metabolic Service, Starship Children's Hospital, Auckland, New Zealand. callumw@adhb.govt.nz FAU - Priore Oliva, Claudio AU - Priore Oliva C FAU - Maggi, Franco AU - Maggi F FAU - Catapano, Alberico L AU - Catapano AL FAU - Calandra, Sebastiano AU - Calandra S LA - eng PT - Case Reports PT - Journal Article PL - United States TA - Ann Neurol JT - Annals of neurology JID - 7707449 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoproteins C) SB - IM MH - Apolipoprotein C-II MH - Apolipoproteins C/*deficiency/*genetics MH - Brain/*metabolism/*pathology MH - DNA Mutational Analysis MH - Diagnosis, Differential MH - Female MH - Humans MH - Hyperlipoproteinemia Type I/*diagnosis/*genetics MH - Infant MH - Infant, Newborn MH - Magnetic Resonance Imaging MH - Point Mutation/genetics MH - Promoter Regions, Genetic/genetics EDAT- 2003/06/05 05:00 MHDA- 2003/07/10 05:00 CRDT- 2003/06/05 05:00 PHST- 2003/06/05 05:00 [pubmed] PHST- 2003/07/10 05:00 [medline] PHST- 2003/06/05 05:00 [entrez] AID - 10.1002/ana.10598 [doi] PST - ppublish SO - Ann Neurol. 2003 Jun;53(6):807-10. doi: 10.1002/ana.10598. PMID- 12775950 OWN - NLM STAT- MEDLINE DCOM- 20031205 LR - 20141120 IS - 1350-6277 (Print) IS - 1350-6277 (Linking) VI - 10 IP - 3 DP - 2003 Jun TI - Statins and oxidative stress during atherogenesis. PG - 181-9 AB - Oxidised low-density lipoprotein (LDL) is believed to be the most atherogenic form of LDL. However, while a number of experimental data support this concept, the protective role of antioxidants that may prevent LDL oxidation in atherosclerosis is only partially confirmed by studies in man. Observational and epidemiological data as well as randomised trials failed to provide clear-cut indications, because of mixed results on the protective role of antioxidants against cardiovascular diseases. In spite of the lack of a general consensus, recent data reinforce the concept that a regular intake of antioxidants present in food blocks the progression of atherosclerosis and that the reduced ability of LDL to oxidise may represent a good marker to follow the action of antioxidants. Among their properties statins also possess antioxidant activities and the aim of this paper is to review the scientific evidence for such an effect and its possible clinical relevance. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milan, and Centro per lo Studio e la Prevenzione delle Vasculopatie Periferiche, Ospedale Bassini, Italy. FAU - Pirillo, Angelo AU - Pirillo A FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - England TA - J Cardiovasc Risk JT - Journal of cardiovascular risk JID - 9436980 RN - 0 (Antioxidants) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) SB - IM MH - Antioxidants/*pharmacology/*therapeutic use MH - Arteriosclerosis/etiology/*physiopathology/*prevention & control MH - Cholesterol, LDL/adverse effects/drug effects/physiology MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology/*therapeutic use MH - In Vitro Techniques MH - Oxidative Stress/*drug effects/*physiology RF - 131 EDAT- 2003/05/31 05:00 MHDA- 2003/12/06 05:00 CRDT- 2003/05/31 05:00 PHST- 2003/05/31 05:00 [pubmed] PHST- 2003/12/06 05:00 [medline] PHST- 2003/05/31 05:00 [entrez] AID - 10.1097/01.hjr.0000071772.88247.14 [doi] PST - ppublish SO - J Cardiovasc Risk. 2003 Jun;10(3):181-9. doi: 10.1097/01.hjr.0000071772.88247.14. PMID- 12690929 OWN - NLM STAT- MEDLINE DCOM- 20030428 LR - 20131121 IS - 1129-4728 (Print) IS - 1129-4728 (Linking) VI - 4 IP - 1 DP - 2003 Jan TI - [Peroxisome proliferator activated receptors and cardiovascular disorders]. PG - 8-18 AB - Peroxisome proliferator activated receptors (PPARs) are transcription factors only recently discovered. Nevertheless, the interest surrounding their study has involved and involves a continuously growing number of researchers. This is due to the role that PPARs play in the understanding of the pathophysiology of clinical conditions such as obesity, diabetes, atherosclerosis, and angiogenesis. Lipid and glucidic metabolism, synthesis of cytokines, adhesion molecules, coagulation factors, fibrinolysis, are only few of the several processes controlled by PPARs. In this review the more recent acquisitions on PPAR mechanisms of action will be described. The clinical implications that their activation/deactivation induce will be also evaluate. Particular emphasis will be placed on their role in the control of the physiology of lipid and glucidic metabolism, as well as in the pathophysiology of inflammatory and atherosclerotic processes. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Laboratorio del Metabolismo Lipoproteico, Centro per lo Studio dell'Aterosclerosi, Dipartimento di Scienze Farmacologiche, Universita degli Studi, Via Balzaretti, 9 20133 Milano. FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Catapano, Alberico Luigi AU - Catapano AL LA - ita PT - English Abstract PT - Journal Article PT - Review TT - "Peroxisome proliferator activated receptors" e patologie cardiovascolari. PL - Italy TA - Ital Heart J Suppl JT - Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology JID - 101223651 RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Transcription Factors) RN - 0 (Triglycerides) RN - Y9449Q51XH (Bezafibrate) SB - IM MH - Bezafibrate/administration & dosage MH - Cardiovascular Diseases/*drug therapy/*metabolism/physiopathology MH - Clinical Trials as Topic MH - Humans MH - Hypolipidemic Agents/*therapeutic use MH - *Lipid Metabolism MH - Lipoproteins, HDL/metabolism MH - Lipoproteins, LDL/metabolism MH - Receptors, Cytoplasmic and Nuclear/*agonists/*metabolism MH - Transcription Factors/*agonists/*metabolism MH - Treatment Outcome MH - Triglycerides/metabolism RF - 73 EDAT- 2003/04/15 05:00 MHDA- 2003/04/29 05:00 CRDT- 2003/04/15 05:00 PHST- 2003/04/15 05:00 [pubmed] PHST- 2003/04/29 05:00 [medline] PHST- 2003/04/15 05:00 [entrez] PST - ppublish SO - Ital Heart J Suppl. 2003 Jan;4(1):8-18. PMID- 12616810 OWN - NLM STAT- MEDLINE DCOM- 20030610 LR - 20071115 IS - 0939-4753 (Print) IS - 0939-4753 (Linking) VI - 12 IP - 5 DP - 2002 Oct TI - Apoptosis and proliferation of endothelial cells in early atherosclerotic lesions: possible role of oxidised LDL. PG - 297-305 AB - BACKGROUND AND AIM: Evidence for apoptosis has been found in advanced atherosclerotic lesions, but the factors triggering it are poorly understood. Oxidised low-density lipoproteins (LDLs) are cytotoxic to a variety of cells and induce the apoptosis of smooth muscle cells (SMC), fibroblast, macrophages and endothelial cells in vitro. The aim of this study was to investigate apoptotic cell death in the early phases of aortic atherosclerosis in rabbits, and whether oxidised LDLs colocalize ex vivo with apoptotic cells in atherosclerotic lesions in cholesterol-fed rabbits. METHODS AND RESULTS: Male albino New Zealand rabbits were fed a standard diet or a diet containing 1.2% cholesterol for 60 days. The aortic arch of each animal was sectioned and stained with antibodies against SMC, endothelial cells, macrophages and oxidised LDLs or for proteins involved in apoptotic pathways such as Fas, Bax, Bcl2, and caspase 3. The nuclei in adjacent sections were stained with Hoechst 33258, TUNEL and for the proliferating cell nuclear antigen (PCNA). Early atherosclerotic lesions were characterised by intimal thickening and the presence of SMC and macrophages. The percentage of apoptotic cells, calculated as the ratio of TUNEL-positive nuclei to total nuclei was 32.6 +/- 3.73% in the lesions and 55.9 +/- 2.36% in the endothelium. As it has been reported that nuclei undergoing active gene transcription can be TUNEL positive, we evaluated the percentage of PCNA-positive cells, which proved to be 45.2 +/- 4.68% along the endothelium and 22.3 +/- 2.7% in the intima. The true percentage of apoptotic cells was therefore about 10% in both cases. Fas, Bax and caspase3 signals were mainly located in the endothelium and SMC proximal to the lumen, whereas Bcl2 colocalized with macrophages and SMC deeper in the lesions. Abundant oxidised LDL epitopes were detected in areas of lipid accumulation and along the endothelium, mainly in the areas in which TUNEL and PCNA-positive cells were localised. CONCLUSIONS: Our findings may be taken as ex vivo indications of an apoptotic and proliferating role of oxidised LDLs as previously shown in vitro, and may at least partially account for the endothelial dysfunction that can be rapidly induced by hypercholesterolemia. FAU - Norata, G D AU - Norata GD AD - Department of Pharmacological Sciences, University of Milano, Italy. FAU - Tonti, L AU - Tonti L FAU - Roma, P AU - Roma P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Antibodies, Monoclonal) RN - 0 (Cholesterol, Dietary) RN - 0 (Lipoproteins, LDL) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - *Apoptosis MH - Cholesterol, Dietary/*administration & dosage MH - Coronary Artery Disease/*metabolism/pathology MH - Endothelium, Vascular/*cytology/immunology/pathology MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Lipoproteins, LDL/metabolism/*physiology MH - Macrophages/immunology/pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Muscle, Smooth, Vascular/cytology/immunology/pathology MH - Oxidation-Reduction MH - Rabbits EDAT- 2003/03/06 04:00 MHDA- 2003/06/11 05:00 CRDT- 2003/03/06 04:00 PHST- 2003/03/06 04:00 [pubmed] PHST- 2003/06/11 05:00 [medline] PHST- 2003/03/06 04:00 [entrez] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2002 Oct;12(5):297-305. PMID- 12374904 OWN - NLM STAT- MEDLINE DCOM- 20030714 LR - 20161020 IS - 0920-3206 (Print) IS - 0920-3206 (Linking) VI - 16 IP - 3 DP - 2002 May TI - Novel statins: pharmacological and clinical results. PG - 251-7 AB - Rosuvastatin (ZD4522) and pitavastatin (NK-104) are novel HMG-CoA reductase inhibitors with a peculiar pharmacological profile. In particular, they show a high potency in decreasing LDL-C and their catabolism is not mediated by the cytochrome P-450 3A4, thus reducing the potential for drug-drug interaction and improving the management of blood cholesterol. As the magnitude of LDL-C reduction is directly associated with the decrease in the incidence of myocardial infarction and mortality for CAD, statins with increased LDL-C lowering potency may ensure the achievement of target LDL-C levels and offer a more aggressive cholesterol control, further improving CAD morbidity and mortality. FAU - Bolego, Chiara AU - Bolego C AD - Nutrition Foundation of Italy, Via S Pietro all'Orto 17, 20121 Milan, Italy. FAU - Poli, Andrea AU - Poli A FAU - Cignarella, Andrea AU - Cignarella A FAU - Catapano, Alberico L AU - Catapano AL FAU - Paoletti, Rodolfo AU - Paoletti R LA - eng PT - Journal Article PT - Review PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 0 (Cholesterol, LDL) RN - 0 (Fluorobenzenes) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (LFA703) RN - 0 (Naphthalenes) RN - 0 (Pyrimidines) RN - 0 (Quinolines) RN - 0 (Sulfonamides) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - M5681Q5F9P (pitavastatin) SB - IM MH - Animals MH - Cholesterol, LDL/blood MH - Clinical Trials as Topic MH - Coronary Disease/blood/etiology/prevention & control MH - Fluorobenzenes/pharmacokinetics/pharmacology/therapeutic use MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology MH - Hypercholesterolemia/complications/drug therapy MH - Naphthalenes/pharmacokinetics/pharmacology/therapeutic use MH - *Pyrimidines MH - Quinolines/pharmacokinetics/pharmacology/therapeutic use MH - Rosuvastatin Calcium MH - *Sulfonamides RF - 53 EDAT- 2002/10/11 04:00 MHDA- 2003/07/15 05:00 CRDT- 2002/10/11 04:00 PHST- 2002/10/11 04:00 [pubmed] PHST- 2003/07/15 05:00 [medline] PHST- 2002/10/11 04:00 [entrez] AID - 5100191 [pii] PST - ppublish SO - Cardiovasc Drugs Ther. 2002 May;16(3):251-7. PMID- 11981074 OWN - NLM STAT- MEDLINE DCOM- 20021008 LR - 20161124 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 17 IP - 5 DP - 2002 May TI - 5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis. PG - 857-64 AB - BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. METHODS: We examined the effect of the active metabolite of folic acid, 5-methyltetrahydrofolate (5-MTHF), 45 mg/week i.v. for 10 weeks, combined during the last 2 weeks with vitamin B12, 500 microg s.c. twice weekly, on homocysteinaemia and endothelial function in 15 patients undergoing convective haemodialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after administration of isosorbide dinitrate. Finally, the presence of the thermolabile variant of methyltetrahydrofolate reductase (t-MTHFR) was assessed by genotype analysis. RESULTS: Plasma homocysteine concentrations fell by 47% after treatment with 5-MTHF alone and by a further 13.6% after the addition of vitamin B12. The reduction was more marked in homo- and heterozygous patients than in normal genotypes for t-MTHFR. Flow-mediated endothelial vasodilation, measured by ultrasonography of the brachial artery, improved after administration of 5-MTHF (12.52+/- 2.47% vs. 7.03+/-1.65%; P<0.05), but there were no further changes following the addition of vitamin B12. CONCLUSIONS: Our study demonstrated that 5-MTHF administration not only reduced plasma homocysteine but also improved endothelial function in uraemic patients undergoing convective haemodialysis. FAU - Buccianti, Gherardo AU - Buccianti G AD - Department of Internal Medicine, Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy. ghbucci@hotmail.com FAU - Raselli, Sara AU - Raselli S FAU - Baragetti, Ivano AU - Baragetti I FAU - Bamonti, Fabrizia AU - Bamonti F FAU - Corghi, Enzo AU - Corghi E FAU - Novembrino, Cristina AU - Novembrino C FAU - Patrosso, Cristina AU - Patrosso C FAU - Maggi, Franco M AU - Maggi FM FAU - Catapano, Alberico L AU - Catapano AL LA - eng PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Tetrahydrofolates) RN - 0LVT1QZ0BA (Homocysteine) RN - P6YC3EG204 (Vitamin B 12) RN - TYK22LML8F (5-methyltetrahydrofolate) SB - IM MH - Drug Therapy, Combination MH - Endothelium, Vascular/diagnostic imaging/*drug effects/*physiopathology MH - Female MH - Genotype MH - Heterozygote MH - Homocysteine/blood MH - Homozygote MH - Humans MH - Injections, Intravenous MH - Injections, Subcutaneous MH - Male MH - Middle Aged MH - *Renal Dialysis MH - Tetrahydrofolates/administration & dosage/*therapeutic use MH - Ultrasonography MH - Uremia/genetics/*physiopathology/*therapy MH - Vasodilation/drug effects MH - Vitamin B 12/administration & dosage/therapeutic use EDAT- 2002/05/01 10:00 MHDA- 2002/10/09 04:00 CRDT- 2002/05/01 10:00 PHST- 2002/05/01 10:00 [pubmed] PHST- 2002/10/09 04:00 [medline] PHST- 2002/05/01 10:00 [entrez] PST - ppublish SO - Nephrol Dial Transplant. 2002 May;17(5):857-64. PMID- 11679276 OWN - NLM STAT- MEDLINE DCOM- 20020225 LR - 20141120 IS - 0956-5663 (Print) IS - 0956-5663 (Linking) VI - 16 IP - 9-12 DP - 2001 Dec TI - Epitope mapping analysis of apolipoprotein B-100 using a surface plasmon resonance-based biosensor. PG - 963-9 AB - Using a surface plasmon resonance (SPR)-based biosensor (BIA-technology), we have studied the interaction of ten different murine monoclonal antibodies (mAbs, all IgG(1)), raised against the main protein constituent of human low density lipoprotein (LDL), i.e. the apolipoprotein B-100 (apoB-100). These mAbs identify distinct domains on apoB-100, relevant to LDL-receptor interaction: epitopes in the amino-terminal region (mAbs L7, L9, L10 and L11: aa 1-1297) and in the middle region (mAb 6B: aa 1480-1693; mAbs 2A, 3B: aa 2152-2377; mAbs 9A, L2 and L4: aa 2657-3248) of native apoB-100. A multisite binding analysis was performed to further characterize the epitopes recognized by all these mAbs. A rabbit anti-mouse IgG(1)-Fc antibody (RAM.Fc) was first coupled to the gold surface in order to capture one anti-human apoB-100 mAb. ApoB-100 protein was subsequently injected and allowed to react with this immobilized, oriented antibody. Multisite binding assays were then performed, by sequentially flowing other mAbs, in different orders, over the sensing surface. The capacity of each mAb to interact with the entrapped apoB-100 in a multimolecular complex was monitored in real time by SPR. The results achieved were comparable to those obtained by western immunoblotting using the same reagents. However, SPR ensures a more detailed epitope identification, demonstrating that BIA-technology can be successfully used for mapping distinct epitopes on apoB-100 protein in solution dispensing with labels and secondary tracers; moreover, compared with conventional immunoassays, it is significantly time saving (CNR-P.F. MADESS 2). FAU - Laricchia Robbio, L AU - Laricchia Robbio L AD - Institute of Mutagenesis and Differentiation, CNR, Area della Ricerca San Cataldo, 56100 Via Moruzzi, Ghezzano-Pisa, Italy. lel@imd.pi.cnr.it FAU - Uboldi, P AU - Uboldi P FAU - Marcovina, S AU - Marcovina S FAU - Revoltella, R P AU - Revoltella RP FAU - Catapano, A L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Biosens Bioelectron JT - Biosensors & bioelectronics JID - 9001289 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoproteins B) RN - 0 (Ligands) RN - 0 (Receptors, LDL) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - Apolipoprotein B-100 MH - Apolipoproteins B/*analysis/*immunology/metabolism MH - Epitope Mapping/*methods MH - Humans MH - Immunoassay/methods MH - In Vitro Techniques MH - Ligands MH - Mice MH - Receptors, LDL/metabolism MH - Surface Plasmon Resonance/*methods EDAT- 2001/10/27 10:00 MHDA- 2002/02/28 10:01 CRDT- 2001/10/27 10:00 PHST- 2001/10/27 10:00 [pubmed] PHST- 2002/02/28 10:01 [medline] PHST- 2001/10/27 10:00 [entrez] AID - S0956566301002445 [pii] PST - ppublish SO - Biosens Bioelectron. 2001 Dec;16(9-12):963-9. PMID- 11231913 OWN - NLM STAT- MEDLINE DCOM- 20010517 LR - 20131121 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 21 IP - 3 DP - 2001 Mar TI - Overexpression of inducible heat shock protein 70 in Cos-1 cells fails to protect from cytotoxicity of oxidized ldls. PG - 348-54 AB - Oxidized low density lipoproteins (OxLDLs) are believed to play a central role in atherogenesis and to possess a wide variety of biological properties; among them, OxLDLs are cytotoxic to cultured vascular cells in that they induce necrosis and apoptosis. Moreover, OxLDLs are known to induce the expression of heat shock protein 70 (Hsp70), a protein that protects cells from several cytotoxic stimuli. To determine whether Hsp70 can protect cells against OxLDL-induced cytotoxicity, COS-1 cells were transfected with a construct containing human Hsp70. A number of cell lines permanently expressing Hsp70 were obtained, 1 of which (cos-Hsp70/10, with high Hsp70 expression) was selected for further studies. Hsp70 overexpression protected cells from toxic stimuli, such as H(2)O(2), UV irradiation, and heat shock, suggesting that the overexpressed protein was functional. When incubated with OxLDLs, however, the clone overexpressing Hsp70 showed a significant decrease in viability, as determined by the [(3)H]adenine release assay (319.8+/-3.16% of control for transfected cells versus 217.6+/-6.08% for control cells exposed to 100 microgram protein/mL of OxLDL), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (12.5+/-0.9% versus 28.9+/-1.99% of control, respectively), and LDH release (48.4+/-0.04% versus 15.2+/-0.06% of control cells). The increased expression of BAX and the decreased expression of Bcl-2 (a proapoptotic and an antiapoptotic protein, respectively) in cos-Hsp70/10 cells and in control cells on incubation with OxLDLs suggested that overexpression of Hsp70 did not confer protection against apoptosis induced by OxLDLs. The analysis of nucleosome content and the nuclear staining with Hoechst 33258 confirmed this finding. These data suggest that overexpression of Hsp70 not only fails to protect COS-1 cells against OxLDL-induced apoptosis but rather confers a higher sensitivity to the cytotoxic action of these lipoproteins. Thus, the Hsp70 response, although induced by OxLDLs, cannot protect cells from lipoprotein toxicity. FAU - Pirillo, A AU - Pirillo A AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Norata, G D AU - Norata GD FAU - Zanelli, T AU - Zanelli T FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Lipoproteins, LDL) RN - 0 (Nucleosomes) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-2-Associated X Protein) RN - 0 (oxidized low density lipoprotein) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Animals MH - COS Cells MH - Cell Nucleus/drug effects MH - Cell Size/drug effects MH - Cell Survival/*drug effects/radiation effects MH - Gene Expression Regulation MH - HSP70 Heat-Shock Proteins/genetics/*metabolism MH - Hydrogen Peroxide/pharmacology MH - Lipoproteins, LDL/*toxicity MH - Nucleosomes/drug effects/metabolism MH - Plasmids/genetics MH - Proto-Oncogene Proteins/drug effects/metabolism MH - Proto-Oncogene Proteins c-bcl-2/drug effects/metabolism MH - Transfection MH - Ultraviolet Rays MH - bcl-2-Associated X Protein EDAT- 2001/03/07 10:00 MHDA- 2001/05/22 10:01 CRDT- 2001/03/07 10:00 PHST- 2001/03/07 10:00 [pubmed] PHST- 2001/05/22 10:01 [medline] PHST- 2001/03/07 10:00 [entrez] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2001 Mar;21(3):348-54. PMID- 11110410 OWN - NLM STAT- MEDLINE DCOM- 20001222 LR - 20181130 IS - 0969-7128 (Print) IS - 0969-7128 (Linking) VI - 7 IP - 21 DP - 2000 Nov TI - Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA. PG - 1795-801 AB - We report on systemic delivery and long-term biological effects of apolipoprotein E (apoE) obtained by intramuscular (i.m.) plasmid DNA injection. ApoE plays an important role in lipoprotein catabolism and apoE knock-out mice develop severe hypercholesterolemia and diffuse atherosclerosis. We have injected apoE-deficient mice with 80 microg of a plasmid vector (pCMV-E3) encoding the human apoE3 cDNA under the control of the CMV promoter-enhancer in both posterior legs. Local expression of the transgene was demonstrated throughout 16 weeks. Human apoE3 recombinant protein reached 0.6 ng/ml serum level. After i.m. injection of pCMV-E3 expression vector the mean serum cholesterol concentrations decreased from 439 +/- 57 mg/dl to 253 +/- 99 mg/dl (P < 0.05) 2 weeks after injection and persisted at a significantly reduced level throughout the 16 weeks observation period (P < 0.005). Serum cholesterol was unaffected and reached an absolute level of 636 +/- 67 mg/dl in control groups. Finally, injection of pCMV-E3 into apoE-deficient mice resulted in a redistribution of cholesterol content between lipoprotein fractions, with a marked decrease in VLDL, IDL and LDL cholesterol content and an increase in HDL cholesterol. These results demonstrate that severe hypercholesterolemia in apoE-deficient mice can be effectively reversed by i.m. DNA injection, and indicate that this approach could represent a useful tool to correct several hyperlipidemic conditions resulting in atherosclerosis. FAU - Rinaldi, M AU - Rinaldi M AD - Laboratory for Molecular Medicine and Biotechnology, School of Medicine, Institute of Experimental Medicine, CNR, Rome, Italy. FAU - Catapano, A L AU - Catapano AL FAU - Parrella, P AU - Parrella P FAU - Ciafre, S A AU - Ciafre SA FAU - Signori, E AU - Signori E FAU - Seripa, D AU - Seripa D FAU - Uboldi, P AU - Uboldi P FAU - Antonini, R AU - Antonini R FAU - Ricci, G AU - Ricci G FAU - Farace, M G AU - Farace MG FAU - Fazio, V M AU - Fazio VM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Gene Ther JT - Gene therapy JID - 9421525 RN - 0 (Apolipoproteins E) RN - 0 (DNA, Complementary) RN - 0 (Lipoproteins) RN - 0 (RNA, Messenger) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Analysis of Variance MH - Animals MH - Apolipoproteins E/*deficiency/*genetics/metabolism MH - Cholesterol/blood MH - Cytomegalovirus/genetics MH - DNA, Complementary/*administration & dosage MH - Enzyme-Linked Immunosorbent Assay/methods MH - Gene Expression MH - Genetic Therapy/*methods MH - Genetic Vectors/*administration & dosage MH - Injections, Intramuscular MH - Lipoproteins/blood MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Skeletal/chemistry/metabolism MH - Promoter Regions, Genetic MH - RNA, Messenger/analysis MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2000/12/08 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/12/08 11:00 PHST- 2000/12/08 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/12/08 11:00 [entrez] AID - 10.1038/sj.gt.3301310 [doi] PST - ppublish SO - Gene Ther. 2000 Nov;7(21):1795-801. doi: 10.1038/sj.gt.3301310. PMID- 11128189 OWN - NLM STAT- MEDLINE DCOM- 20010125 LR - 20071115 IS - 0268-4705 (Print) IS - 0268-4705 (Linking) VI - 15 IP - 5 DP - 2000 Sep TI - Low density lipoprotein oxidation, antioxidants, and atherosclerosis. PG - 355-63 AB - Oxidized low density lipoproteins (LDLs) are believed to be the most atherogenic form of LDL. However, although a number of experimental data support this concept, the protective role of antioxidants that may prevent LDL oxidation in atherosclerosis is only partially confirmed by studies in humans. Observational and epidemiologic data as well as randomized trials failed to provide clear-cut indications because of mixed results on the protective role of antioxidants against cardiovascular diseases. In spite of the lack of a general consensus, recent data reinforce the concept that a regular intake of antioxidants present in food blocks the progression of atherosclerosis and that the reduced oxidisability of LDL may represent a good marker to follow the action of antioxidants. When it becomes possible to monitor the efficacy of any antioxidant therapy with validated markers of oxidation, the potential influence of vitamins and antioxidants on coronary artery disease will eventually be resolved. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milan, Italy. alberico.catapano@unimi.it FAU - Maggi, F M AU - Maggi FM FAU - Tragni, E AU - Tragni E LA - eng PT - Journal Article PT - Review PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - 0 (Antioxidants) RN - 0 (Lipoproteins, LDL) SB - IM CIN - Curr Opin Cardiol. 2000 Sep;15(5):343-7. PMID: 11128187 MH - Antioxidants/*therapeutic use MH - Arteriosclerosis/*metabolism/*prevention & control MH - Humans MH - Lipoproteins, LDL/*metabolism MH - Male MH - Oxidation-Reduction MH - Randomized Controlled Trials as Topic RF - 100 EDAT- 2000/12/29 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/12/29 11:00 PHST- 2000/12/29 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/12/29 11:00 [entrez] PST - ppublish SO - Curr Opin Cardiol. 2000 Sep;15(5):355-63. PMID- 10828090 OWN - NLM STAT- MEDLINE DCOM- 20000802 LR - 20131121 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 41 IP - 6 DP - 2000 Jun TI - Identification of domains in apoA-I susceptible to proteolysis by mast cell chymase. Implications for HDL function. PG - 975-84 AB - When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Mabs) against functional domains of apoA-I. Size exclusion chromatography of HDL(3) revealed that proteolysis for up to 24 h did not alter the integrity of the alpha-migrating HDL, whereas a minor peak containing particles of smaller size with prebeta mobility disappeared after as little as 15 min of incubation. At the same time, generation of a large (26 kDa) polypeptide containing the N-terminus of apoA-I was detected. This large fragment and other medium-sized fragments of apoA-I produced after prolonged treatment with chymase were found to be associated with the alphaHDL; meanwhile, small lipid-free peptides were rapidly produced. Incubation of HDL(3) with chymase inhibited binding of Mab A-I-9 (specific for prebeta(1)HDL) most rapidly (within 15 min) of the eight studied Mabs. This rapid loss of binding was paralleled by a similar reduction in the ability of HDL(3) to induce high-affinity efflux of cholesterol from macrophage foam cells, indicating that proteolysis had destroyed an epitope that is critical for this function. In sharp contrast, prolonged degradation of HDL(3) by chymase failed to reduce the ability of HDL(3) to activate LCAT, even though it led to modification of three epitopes in the central region of apoA-I that are involved in lecithin cholesterol acyltransferase (LCAT) activation. This differential sensitivity of the two key functions of HDL(3) to the proteolytic action of mast cell chymase is compatible with the notion that, in reverse cholesterol transport, intactness of apoA-I is essential for prebeta(1)HDL to promote the high-affinity efflux of cellular cholesterol, but not for the alpha-migrating HDL particles to activate LCAT. FAU - Lee, M AU - Lee M AD - Wihuri Research Institute, Kalliolinnantie 4, Helsinki 00140, Finland. FAU - Uboldi, P AU - Uboldi P FAU - Giudice, D AU - Giudice D FAU - Catapano, A L AU - Catapano AL FAU - Kovanen, P T AU - Kovanen PT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein A-I) RN - 0 (Lipoproteins, HDL) RN - 97C5T2UQ7J (Cholesterol) RN - EC 2.3.1.43 (Phosphatidylcholine-Sterol O-Acyltransferase) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.39 (Chymases) SB - IM MH - Animals MH - Antibodies, Monoclonal/immunology MH - Apolipoprotein A-I/immunology/*metabolism MH - Cholesterol/metabolism MH - Chymases MH - Enzyme Activation MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Foam Cells/metabolism MH - Hydrolysis MH - Lipoproteins, HDL/*metabolism MH - Male MH - Mast Cells/*enzymology MH - Mice MH - Phosphatidylcholine-Sterol O-Acyltransferase/isolation & purification/metabolism MH - Rats MH - Rats, Wistar MH - Serine Endopeptidases/*metabolism EDAT- 2000/05/29 09:00 MHDA- 2000/08/06 11:00 CRDT- 2000/05/29 09:00 PHST- 2000/05/29 09:00 [pubmed] PHST- 2000/08/06 11:00 [medline] PHST- 2000/05/29 09:00 [entrez] PST - ppublish SO - J Lipid Res. 2000 Jun;41(6):975-84. PMID- 10834403 OWN - NLM STAT- MEDLINE DCOM- 20000918 LR - 20161018 IS - 1434-6621 (Print) IS - 1434-6621 (Linking) VI - 38 IP - 2 DP - 2000 Feb TI - Oxidized lipoproteins and endothelium. PG - 155-60 AB - Endothelium is an early target of pro-atherosclerotic events, which may result in functional and morphological perturbations. Oxidized low density lipoproteins, an atherogenic factor with strong cytotoxicity, may potentially contribute to altered endothelial function through the activation of a stress response, which would rescue cells to full vitality, or, conversely, by leading to cell death. Evidence is presented here for the ability of chemically oxidized low density lipoproteins to induce the synthesis of the inducible form of heat shock protein 70 in cultured human endothelial cells, and for the association of epitopes of these modified lipoproteins with apoptotic endothelial cells in aortic sections from hypercholesterolemic rabbits. FAU - Pirillo, A AU - Pirillo A AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Zhu, W AU - Zhu W FAU - Norata, G D AU - Norata GD FAU - Zanelli, T AU - Zanelli T FAU - Barberi, L AU - Barberi L FAU - Roma, P AU - Roma P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Clin Chem Lab Med JT - Clinical chemistry and laboratory medicine JID - 9806306 RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Lipoproteins, LDL) RN - 0 (oxidized low density lipoprotein) RN - AGG2FN16EV (Simvastatin) SB - IM MH - Animals MH - Apoptosis MH - Arteriosclerosis/etiology/metabolism/pathology MH - Cells, Cultured MH - Endothelium, Vascular/drug effects/*metabolism/pathology MH - HSP70 Heat-Shock Proteins/biosynthesis MH - Humans MH - Hypercholesterolemia/metabolism/pathology MH - In Vitro Techniques MH - Lipoproteins, LDL/*metabolism/pharmacology MH - Male MH - Oxidation-Reduction MH - Rabbits MH - Simvastatin/pharmacology EDAT- 2000/06/02 09:00 MHDA- 2000/09/23 11:01 CRDT- 2000/06/02 09:00 PHST- 2000/06/02 09:00 [pubmed] PHST- 2000/09/23 11:01 [medline] PHST- 2000/06/02 09:00 [entrez] AID - 10.1515/CCLM.2000.023 [doi] PST - ppublish SO - Clin Chem Lab Med. 2000 Feb;38(2):155-60. doi: 10.1515/CCLM.2000.023. PMID- 12497838 OWN - NLM STAT- MEDLINE DCOM- 20030312 LR - 20141120 IS - 0393-1978 (Print) IS - 0393-1978 (Linking) VI - 44 Suppl 1 IP - Pt 2 DP - 1999 Dec TI - [Relationship between hypercholesterolemia and coronary disease: Italian data and international data]. PG - 869-73 FAU - Catapano, A L AU - Catapano AL AD - Istituto di Scienze Farmacologiche, Centro Studi Aterosclerosi Universita degli Studi Via Balzaretti, 9, 20133 Milano. FAU - Poli, A AU - Poli A FAU - Tragni, E AU - Tragni E LA - ita PT - Journal Article TT - Relazione tra ipercolesterolemia e malattia coronarica: dati italiani e dati internazionali. PL - Italy TA - Cardiologia JT - Cardiologia (Rome, Italy) JID - 8506637 SB - IM MH - Coronary Disease/epidemiology/*etiology MH - Global Health MH - Humans MH - Hypercholesterolemia/*complications MH - Italy EDAT- 2002/12/25 04:00 MHDA- 2003/03/13 04:00 CRDT- 2002/12/25 04:00 PHST- 2002/12/25 04:00 [pubmed] PHST- 2003/03/13 04:00 [medline] PHST- 2002/12/25 04:00 [entrez] PST - ppublish SO - Cardiologia. 1999 Dec;44 Suppl 1(Pt 2):869-73. PMID- 10580102 OWN - NLM STAT- MEDLINE DCOM- 20000113 LR - 20141120 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 462 IP - 1-2 DP - 1999 Nov 26 TI - Oxysterols from oxidized LDL are cytotoxic but fail to induce hsp70 expression in endothelial cells. PG - 113-6 AB - Oxidized low density lipoprotein (OxLDL) possesses several proatherogenic characteristics, among which a marked cytotoxicity. In vitro, cytotoxicity of OxLDL to endothelial cells is associated with an increase in the expression of the inducible form of heat shock protein 70 (hsp70), generally regarded as a cytoprotective protein. Oxidized derivatives of cholesterol which form upon LDL oxidation are cytotoxic. Moreover, most of the OxLDL cytotoxicity is due to its lipid moiety, in particular to oxysterols. In this report we demonstrate that although oxysterols identified in OxLDL are cytotoxic, they cannot trigger the increase in hsp70 expression observed with intact oxidized lipoproteins. We speculate therefore that oxysterols may represent the most toxic form of oxidized lipids in LDL because they cannot activate a rescue mechanism (i.e. the hsp response) and may contribute significantly to cell death within atherosclerotic plaques. FAU - Pirillo, A AU - Pirillo A AD - Institute of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133, Milano, Italy. FAU - Zhu, W AU - Zhu W FAU - Roma, P AU - Roma P FAU - Galli, G AU - Galli G FAU - Caruso, D AU - Caruso D FAU - Pellegatta, F AU - Pellegatta F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Hydroxycholesterols) RN - 0 (Ketocholesterols) RN - 0 (Lipoproteins, LDL) RN - 0 (oxidized low density lipoprotein) RN - O7676FE78M (7-ketocholesterol) SB - IM MH - Apoptosis MH - Endothelium, Vascular/*metabolism/pathology MH - Gene Expression MH - HSP70 Heat-Shock Proteins/*biosynthesis MH - Humans MH - Hydroxycholesterols/metabolism MH - In Vitro Techniques MH - Ketocholesterols/metabolism MH - Lipoproteins, LDL/*metabolism MH - Oxidation-Reduction EDAT- 1999/12/02 00:00 MHDA- 1999/12/02 00:01 CRDT- 1999/12/02 00:00 PHST- 1999/12/02 00:00 [pubmed] PHST- 1999/12/02 00:01 [medline] PHST- 1999/12/02 00:00 [entrez] AID - S0014-5793(99)01497-0 [pii] PST - ppublish SO - FEBS Lett. 1999 Nov 26;462(1-2):113-6. PMID- 11122714 OWN - NLM STAT- MEDLINE DCOM- 20010712 LR - 20181113 IS - 1523-3804 (Print) IS - 1523-3804 (Linking) VI - 1 IP - 3 DP - 1999 Nov TI - Antioxidants and coronary artery disease. PG - 221-9 AB - The protective role of antioxidants in experimental models of atherosclerosis is only partially confirmed by studies in man. Observational and epidemiologic data, as well as randomized trials failed to provide clear cut indications, because of mixed results on the protective role of antioxidants against cardiovascular diseases. In spite of the lack of a general consensus, recent data reinforce the concept that a regular intake of antioxidants present in food limits the progression of atherosclerosis. When it will be possible to monitor the efficacy of any antioxidant therapy with validated markers of oxidation, the potential influence of vitamins and antioxidants on coronary artery disease may eventually be resolved. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, I-20133 Milan, Italy. FAU - Tragni, E AU - Tragni E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Antioxidants) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Coronary Disease/etiology/*prevention & control MH - Diet MH - Disease Models, Animal MH - Disease Progression MH - Humans MH - Randomized Controlled Trials as Topic RF - 80 EDAT- 2000/12/21 11:00 MHDA- 2001/07/13 10:01 CRDT- 2000/12/21 11:00 PHST- 2000/12/21 11:00 [pubmed] PHST- 2001/07/13 10:01 [medline] PHST- 2000/12/21 11:00 [entrez] PST - ppublish SO - Curr Atheroscler Rep. 1999 Nov;1(3):221-9. PMID- 10551656 OWN - NLM STAT- MEDLINE DCOM- 19991116 LR - 20131121 IS - 0041-1337 (Print) IS - 0041-1337 (Linking) VI - 68 IP - 8 DP - 1999 Oct 27 TI - Trimetazidine counteracts tacrolimus nephrotoxicity in a hypertensive liver transplant patient. PG - 1211 FAU - Zoppo, A AU - Zoppo A FAU - Faggiotto, A AU - Faggiotto A FAU - Redaelli, L AU - Redaelli L FAU - Campi, S AU - Campi S FAU - Catapano, A L AU - Catapano AL LA - eng PT - Case Reports PT - Letter PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Immunosuppressive Agents) RN - 0 (Vasodilator Agents) RN - N9A0A0R9S8 (Trimetazidine) RN - WM0HAQ4WNM (Tacrolimus) SB - IM MH - Humans MH - Hypertension/*complications MH - Immunosuppressive Agents/*adverse effects/antagonists & inhibitors MH - Kidney Diseases/*chemically induced/drug therapy MH - Liver Cirrhosis/complications/*surgery MH - *Liver Transplantation MH - Tacrolimus/*adverse effects/antagonists & inhibitors MH - Trimetazidine/*therapeutic use MH - Vasodilator Agents/*therapeutic use EDAT- 1999/11/07 00:00 MHDA- 1999/11/07 00:01 CRDT- 1999/11/07 00:00 PHST- 1999/11/07 00:00 [pubmed] PHST- 1999/11/07 00:01 [medline] PHST- 1999/11/07 00:00 [entrez] PST - ppublish SO - Transplantation. 1999 Oct 27;68(8):1211. PMID- 10487482 OWN - NLM STAT- MEDLINE DCOM- 19991028 LR - 20061115 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 146 IP - 1 DP - 1999 Sep TI - A successful dietary treatment fails to normalize plasma triglyceride postprandial response in type IV patients. PG - 19-23 AB - The role of plasma triglycerides as a risk factor for cardiovascular disease is still under scrutiny. While recent studies have shown that postprandial triglyceridemia is an independent risk factor, normalization of fasting plasma triglycerides through modification of nutritional habits remains the primary approach in the treatment of hypertriglyceridemia. To address the issue of whether a satisfactory dietary regimen results in the control of postprandial lipemia, 53 type IV hypertriglyceridemic patients underwent an hypolipidemic diet for 3 months. All patients had a reduction of fasting lipid parameters (average TG: from 516+/-208 to 229+/-99 mg/dl; total cholesterol (Chol): from 261+/-42 to 213+/-40 mg/dl and HDL Chol: from 33+/-9 to 38+/-8 mg/dl). Taking plasma TG < or =200 mg/dl as the target for dietary intervention 26 patients were classified as 'responders' while the remaining 27 were 'non responders'. Even if fasting total TG, total Chol, HDL and LDL Chol were normal, both responders and non responders (P<0.0001) showed an exaggerated postprandial response to an oral fat load as compared to controls (20 normolipidemic subjects). Also when 10 responders and 10 controls, all male, were matched for plasma TG (129+/-43 versus 121+/-41 mg/dl) and other lipid parameters, a statistically significant difference between the two groups was observed at the time of each of the postprandial tests (P<0.0001) and for the area under the curve. The fact that the post prandial response is poorly modified by a dietary regimen, that effectively reduces plasma fasting TG, suggests that commonly used dietary regimens fail to restore a normal postprandial metabolism. Whether the cardiovascular risk for these patients is reduced after diet remains, therefore, to be addressed. FAU - Zoppo, A AU - Zoppo A AD - Centro per lo Studio dell'Aterosclerosi, University of Milan, Italy. FAU - Maggi, F M AU - Maggi FM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Clinical Trial PT - Comparative Study PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Triglycerides) SB - IM MH - Adult MH - Analysis of Variance MH - Diet, Atherogenic MH - Female MH - Humans MH - Hyperlipoproteinemia Type IV/diagnosis/*diet therapy/metabolism MH - Male MH - Middle Aged MH - Postprandial Period MH - Treatment Failure MH - Triglycerides/*blood/metabolism EDAT- 1999/09/16 00:00 MHDA- 1999/09/16 00:01 CRDT- 1999/09/16 00:00 PHST- 1999/09/16 00:00 [pubmed] PHST- 1999/09/16 00:01 [medline] PHST- 1999/09/16 00:00 [entrez] AID - S0021-9150(99)00121-5 [pii] PST - ppublish SO - Atherosclerosis. 1999 Sep;146(1):19-23. PMID- 10428299 OWN - NLM STAT- MEDLINE DCOM- 19990908 LR - 20181201 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 145 IP - 1 DP - 1999 Jul TI - NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, decreases apolipoprotein B-100 secretion from Hep G2 cells. PG - 87-95 AB - Intracellular cholesterol biosynthesis may play a key role in supplying cholesterol (as cholesteryl ester) for the neutral core of very low density lipoprotein (VLDL), thus modulating the secretion of apolipoprotein B-100 (apo B-100) from hepatocytes. The effect of compound NK-104 was studied, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA-reductase), on apo B-100 synthesis and secretion from the human hepatoma cell line Hep G2. Cells were preincubated with NK-104 (0.01-5 microM) in the presence or absence of oleate (0.8 mM). Apo B-100 in the medium was determined by an enzyme-linked immunosorbent assay (ELISA). Incubation of Hep G2 with NK-104 resulted in a marked inhibition of cholesterogenesis (up to 95%), determined as incorporation of [14C]acetate into sterols, and decreased in a dose-dependent manner apo B-100 secretion, both in basal conditions (from 110 to 82 ng/mg cell protein, P < 0.01) and after incubation with oleate (from 227 to 165 ng/mg cell protein, P < 0.01). Density gradient for distribution of apo B-100 secreted, showed that this decrease was essentially due to a reduction of apo B-100 associated with lipoproteins in the density range of low density lipoproteins (LDL). Pulse chase experiment demonstrated that NK-104 did not affect the synthetic rate of apo B-100 but increased intracellular degradation of newly synthesized protein. The compound had only marginal effect on the mass of intracellular triglyceride but significantly decreased intracellular mass of free cholesterol and cholesteryl ester (P < 0.01). It is speculated that the ability of compound NK-104 to decrease apo B-100 secretion from Hep G2 cells is due to a decreased intracellular cholesterol availability. FAU - Ooyen, C AU - Ooyen C AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Zecca, A AU - Zecca A FAU - Bersino, A M AU - Bersino AM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoproteins B) RN - 0 (Enzyme Inhibitors) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Quinolines) RN - 97C5T2UQ7J (Cholesterol) RN - M5681Q5F9P (pitavastatin) SB - IM MH - Apolipoprotein B-100 MH - Apolipoproteins B/drug effects/*metabolism MH - Cholesterol/metabolism MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/*pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology MH - In Vitro Techniques MH - Lipid Metabolism MH - Liver/*metabolism MH - Quinolines/*pharmacology MH - Tumor Cells, Cultured/metabolism EDAT- 1999/07/31 00:00 MHDA- 1999/07/31 00:01 CRDT- 1999/07/31 00:00 PHST- 1999/07/31 00:00 [pubmed] PHST- 1999/07/31 00:01 [medline] PHST- 1999/07/31 00:00 [entrez] AID - S0021-9150(99)00018-0 [pii] PST - ppublish SO - Atherosclerosis. 1999 Jul;145(1):87-95. PMID- 9884075 OWN - NLM STAT- MEDLINE DCOM- 19990401 LR - 20121115 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 125 IP - 7 DP - 1998 Dec TI - Effect of lercanidipine and its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits. PG - 1471-6 AB - The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two different types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. Lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) as well as its (R)-enantiomer at 3 mg kg(-1) week(-1) were given by subcutaneous injection for 10 weeks to White New Zealand rabbits, with cholesterol feeding beginning at week 2. The hyperplastic lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty streak lesions were induced by cholesterol feeding. In untreated animals (n=5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries without collar showed a intima/media (I/M) ratio of 0.03+/-0.02, whereas in carotids with a collar the ratio was 2+/-0.42. In lercanidipine-treated animals a significant and dose-dependent effect on intimal hyperplasia was observed. I/M ratios were 0.73+/-0.4, 0.42+/-0.1, 0.32+/-0.1 for 0.3, 1, and 3 mg kg(-1) week(-1), respectively (P<0.05). The lercanidipine enantiomer (3 mg kg(-1) week(-1)) was as effective as the racemate (0.41+/-0.11). Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) and its (R)-enantiomer, respectively. The area of fatty-streaks in the aorta (n = 11-15) was significantly reduced by lercanidipine (3 mg kg(-1) week(-1), 16% vs 27%, P<0.05), a trend was observed also with lower doses. When different segments of the aorta were considered (arch, thoracic, abdominal) a significant and dose-dependent effect in the thoracic and abdominal aorta was observed also at lower doses. The (R)-enantiomer was as effective as lercanidipine. These results suggest a direct antiatherosclerotic effect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity. FAU - Soma, M R AU - Soma MR AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Natali, M AU - Natali M FAU - Donetti, E AU - Donetti E FAU - Baetta, R AU - Baetta R FAU - Farina, P AU - Farina P FAU - Leonardi, A AU - Leonardi A FAU - Comparato, C AU - Comparato C FAU - Barberi, L AU - Barberi L FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Calcium Channel Blockers) RN - 0 (Cholesterol, Dietary) RN - 0 (Dihydropyridines) RN - V7XTJ4R0BH (lercanidipine) SB - IM MH - Animals MH - Arteries/metabolism MH - Arteriosclerosis/*drug therapy/etiology MH - Calcium Channel Blockers/chemistry/*therapeutic use MH - Cholesterol, Dietary/adverse effects MH - Dihydropyridines/chemistry/*therapeutic use MH - Disease Models, Animal MH - Hypercholesterolemia/complications/*drug therapy MH - Hyperplasia/drug therapy MH - Macrophages/metabolism MH - Male MH - Rabbits PMC - PMC1565732 EDAT- 1999/01/12 00:00 MHDA- 1999/01/12 00:01 CRDT- 1999/01/12 00:00 PHST- 1999/01/12 00:00 [pubmed] PHST- 1999/01/12 00:01 [medline] PHST- 1999/01/12 00:00 [entrez] AID - 10.1038/sj.bjp.0702221 [doi] PST - ppublish SO - Br J Pharmacol. 1998 Dec;125(7):1471-6. doi: 10.1038/sj.bjp.0702221. PMID- 9868589 OWN - NLM STAT- MEDLINE DCOM- 19990310 LR - 20051116 IS - 0957-9672 (Print) IS - 0957-9672 (Linking) VI - 9 IP - 6 DP - 1998 Dec TI - Antioxidants and coronary artery disease. PG - 541-9 AB - Data on the protective role of antioxidants in models of atherosclerosis are only partially confirmed in man. Observational and epidemiological data, as well as randomized trials, provide no clear cut indications, because of positive and disappointing results on the use of antioxidants in cardiovascular protection. Despite the lack of a general consensus, recent data reinforce the concept that the regular intake of antioxidants present in food limits the progression of atherosclerosis. When it is possible to monitor the efficacy of any antioxidant therapy with validated markers of oxidation, the potential influence of vitamins and antioxidants on coronary artery disease may eventually be resolved. FAU - Faggiotto, A AU - Faggiotto A AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Poli, A AU - Poli A FAU - Catapano, A L AU - Catapano AL LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PT - Review PL - England TA - Curr Opin Lipidol JT - Current opinion in lipidology JID - 9010000 RN - 0 (Antioxidants) RN - 0 (Minerals) SB - IM MH - Adult MH - Aged MH - Antioxidants/*therapeutic use MH - Coronary Disease/*drug therapy MH - Female MH - Food MH - Humans MH - Male MH - Middle Aged MH - Minerals/administration & dosage RF - 74 EDAT- 1998/12/30 00:00 MHDA- 1998/12/30 00:01 CRDT- 1998/12/30 00:00 PHST- 1998/12/30 00:00 [pubmed] PHST- 1998/12/30 00:01 [medline] PHST- 1998/12/30 00:00 [entrez] PST - ppublish SO - Curr Opin Lipidol. 1998 Dec;9(6):541-9. PMID- 9863537 OWN - NLM STAT- MEDLINE DCOM- 19990225 LR - 20181201 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 141 IP - 1 DP - 1998 Nov TI - Dual effects of the antioxidant agents probucol and carvedilol on proliferative and fatty lesions in hypercholesterolemic rabbits. PG - 45-51 AB - The in vivo direct antiatherogenic activity of the antioxidant probucol (200 mg/kg per day) or the beta-blocker with antioxidant properties carvedilol (10 and 20 mg/kg per day) was tested in the same animal in two different types of atherosclerotic lesion (proliferative and fatty lesions) induced in cholesterol-fed rabbits (1%). Drugs were given daily mixed with standard diet for 8 weeks; body weight and plasma lipid profile were not different among groups throughout the study. Aortic fatty lesions were induced by cholesterol feeding (n = 25 in each group) and their extent expressed as % of aorta inner surface covered by plaques was significantly reduced by both drugs (28.2+/-9.6%, P <0.05, 19.9+/-6.2%, P <0.01 for low- and high-dose carvedilol, respectively; 22.3+/-7.6%, P <0.01 for probucol, versus 41.6+/-10.7% in control rabbits). Proliferative lesions were obtained by positioning a hollow silastic collar around one carotid artery 6 weeks after dietary and drug treatments started (n = 5 in each group). The neointimal formation, mostly composed by myocytes, was determined by measuring cross-sectional thickness ratio of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals, collared arteries resulted in a significant neointimal cell accumulation compared to the sham (1.10+/-0.14 versus 0.02+/-0.01) without change in medial thickness. I/M ratio was reduced by about 50% in animals treated with probucol (0.51+/-0.1) and carvedilol (0.66+/-0.21 and 0.52+/-0.1 in the low- and high-dose group, respectively). Total plasma TBARS were more than 50% lower in both probucol- and high-dose carvedilol-treated rabbits. Results show that pharmacological pretreatment with antioxidants directly inhibits early atherogenic processes, representing a potentially useful approach in the prevention of atherosclerosis. FAU - Donetti, E AU - Donetti E AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Soma, M R AU - Soma MR FAU - Barberi, L AU - Barberi L FAU - Paoletti, R AU - Paoletti R FAU - Fumagalli, R AU - Fumagalli R FAU - Roma, P AU - Roma P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Anticholesteremic Agents) RN - 0 (Antihypertensive Agents) RN - 0 (Antioxidants) RN - 0 (Carbazoles) RN - 0 (Propanolamines) RN - 0K47UL67F2 (Carvedilol) RN - P3CTH044XJ (Probucol) SB - IM MH - Adrenergic beta-Antagonists/*pharmacology MH - Animals MH - Anticholesteremic Agents/*pharmacology MH - Antihypertensive Agents/pharmacology MH - Antioxidants/*pharmacology MH - Aorta/pathology MH - Arteries/*pathology MH - Arteriosclerosis/complications/*pathology/prevention & control MH - Carbazoles/*pharmacology MH - Carotid Arteries/pathology MH - Carvedilol MH - Cell Division MH - Hypercholesterolemia/complications/*pathology MH - Male MH - Probucol/*pharmacology MH - Propanolamines/*pharmacology MH - Rabbits MH - Tunica Intima/pathology MH - Tunica Media/pathology EDAT- 1998/12/24 00:00 MHDA- 1998/12/24 00:01 CRDT- 1998/12/24 00:00 PHST- 1998/12/24 00:00 [pubmed] PHST- 1998/12/24 00:01 [medline] PHST- 1998/12/24 00:00 [entrez] AID - S0021-9150(98)00146-4 [pii] PST - ppublish SO - Atherosclerosis. 1998 Nov;141(1):45-51. PMID- 9568744 OWN - NLM STAT- MEDLINE DCOM- 19980611 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 137 IP - 1 DP - 1998 Mar TI - Hypobetalipoproteinemia associated with apo B-48.4, a truncated protein only 14 amino acids longer than apo B-48. PG - 125-31 AB - Familial hypobetalipoproteinemia is an autosomal codominant trait that can be caused by mutations in the apo B gene. Here we report a novel apo B gene mutation causing hypobetalipoproteinemia, that is associated with the synthesis of a truncated apo B protein in a young healthy male subject and his mother. The mutation is an A deletion at position 6627 of the apo B cDNA leading to a truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the lipoprotein deficient plasma fraction. Affected family members present with elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles. Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein in the proband showed a normal response to an oral fat load compared to a group of eight matched healthy controls. In summary this novel mutation is associated with hypobetalipoproteinemia with a normal fat absorption as expected for a protein with a length similar to that of apo B-48. FAU - Ruotolo, G AU - Ruotolo G AD - Laboratory of Lipoprotein Metabolism and Atherosclerosis, Istituto Scientifico H San Raffaele, Milan, Italy. giacomo@instmed.ks.se FAU - Zanelli, T AU - Zanelli T FAU - Tettamanti, C AU - Tettamanti C FAU - Ragogna, F AU - Ragogna F FAU - Parlavecchia, M AU - Parlavecchia M FAU - Vigano, F AU - Vigano F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoprotein A-II) RN - 0 (Apolipoprotein B-48) RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoprotein C-III) RN - 0 (Apolipoproteins B) RN - 0 (Apolipoproteins C) RN - 0 (Apolipoproteins E) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Cholesterol, VLDL) RN - 0 (DNA, Complementary) RN - 0 (Oligopeptides) RN - 0 (Triglycerides) RN - 368GB5141J (Sodium Dodecyl Sulfate) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adult MH - Aged MH - Apolipoprotein A-I/blood MH - Apolipoprotein A-II/blood MH - Apolipoprotein B-48 MH - Apolipoprotein C-II MH - Apolipoprotein C-III MH - Apolipoproteins B/analysis/blood/chemistry/*genetics MH - Apolipoproteins C/blood MH - Apolipoproteins E/blood/genetics MH - Base Sequence MH - Cholesterol/blood MH - Cholesterol, HDL/blood/genetics MH - Cholesterol, LDL/blood/genetics MH - Cholesterol, VLDL/blood/genetics MH - DNA Mutational Analysis MH - DNA, Complementary/analysis/genetics MH - Electrophoresis, Polyacrylamide Gel MH - Family Health MH - Female MH - Gene Deletion MH - Humans MH - Hypobetalipoproteinemias/*genetics MH - Immunochemistry MH - Male MH - Middle Aged MH - Mothers MH - Oligopeptides/chemistry/*genetics MH - Pedigree MH - Phenotype MH - Point Mutation/genetics/physiology MH - Sodium Dodecyl Sulfate MH - Triglycerides/blood EDAT- 1998/05/06 00:00 MHDA- 1998/05/06 00:01 CRDT- 1998/05/06 00:00 PHST- 1998/05/06 00:00 [pubmed] PHST- 1998/05/06 00:01 [medline] PHST- 1998/05/06 00:00 [entrez] AID - S0021-9150(97)00262-1 [pii] PST - ppublish SO - Atherosclerosis. 1998 Mar;137(1):125-31. PMID- 9568738 OWN - NLM STAT- MEDLINE DCOM- 19980611 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 137 IP - 1 DP - 1998 Mar TI - Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits. PG - 71-6 AB - The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/-2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels from hypercholesterolemic animals (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus 48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated animals). An antioxidant mechanism is unlikely to explain this data, since Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases. FAU - Hernandez, A AU - Hernandez A AD - Institute of Pharmacological Sciences, Center for Cardiopulmonary Pharmacology, University of Milan, Italy. FAU - Barberi, L AU - Barberi L FAU - Ballerio, R AU - Ballerio R FAU - Testini, A AU - Testini A FAU - Ferioli, R AU - Ferioli R FAU - Bolla, M AU - Bolla M FAU - Natali, M AU - Natali M FAU - Folco, G AU - Folco G FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Cholesterol, Dietary) RN - 0 (Cholesterol, HDL) RN - 0 (Indans) RN - 0 (Triglycerides) RN - 0 (Vasoconstrictor Agents) RN - 0 (Vasodilator Agents) RN - 31C4KY9ESH (Nitric Oxide) RN - 97C5T2UQ7J (Cholesterol) RN - 9G64RSX1XD (Captopril) RN - G59M7S0WS3 (Nitroglycerin) RN - W77UAL9THI (delapril) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Angiotensin-Converting Enzyme Inhibitors/administration & dosage/*pharmacology/therapeutic use MH - Animals MH - Aorta, Abdominal/drug effects/pathology MH - Aorta, Thoracic/drug effects/pathology MH - Arteriosclerosis/chemically induced/*drug therapy/pathology MH - Body Weight/drug effects MH - Captopril/administration & dosage/pharmacology MH - Cholesterol/blood MH - Cholesterol, Dietary/administration & dosage MH - Cholesterol, HDL/blood/drug effects MH - Data Interpretation, Statistical MH - Diet, Atherogenic MH - Disease Models, Animal MH - Disease Progression MH - Dose-Response Relationship, Drug MH - Endothelium, Vascular/*drug effects/physiopathology MH - Hypercholesterolemia/chemically induced/drug therapy/pathology MH - Indans/administration & dosage/*pharmacology/therapeutic use MH - Male MH - Nitric Oxide/metabolism MH - Nitroglycerin/administration & dosage/pharmacology MH - Norepinephrine/administration & dosage/pharmacology MH - Rabbits MH - Triglycerides/blood MH - Vasoconstrictor Agents/administration & dosage/pharmacology MH - Vasodilation/drug effects MH - Vasodilator Agents/administration & dosage/pharmacology EDAT- 1998/05/06 00:00 MHDA- 1998/05/06 00:01 CRDT- 1998/05/06 00:00 PHST- 1998/05/06 00:00 [pubmed] PHST- 1998/05/06 00:01 [medline] PHST- 1998/05/06 00:00 [entrez] AID - S0021-9150(97)00254-2 [pii] PST - ppublish SO - Atherosclerosis. 1998 Mar;137(1):71-6. PMID- 9850438 OWN - NLM STAT- MEDLINE DCOM- 19990303 LR - 20141120 IS - 0803-8023 (Print) IS - 0803-8023 (Linking) VI - 2 DP - 1998 TI - The new calcium antagonist lercanidipine and its enantiomers affect major processes of atherogenesis in vitro: is calcium entry involved? PG - 18-22 AB - Atherosclerosis results from multiple factors and involves several mechanisms, including endothelial monocyte and smooth muscle cell (SMC) changes, cholesterol accumulation, plaque rupture and thromboembolism. Calcium ions play a role in the initial and chronic development of atherosclerotic lesions. Several studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. In this study the antiatherogenic activity of lercanidipine, a new lipophilic, second-generation calcium antagonist, was investigated. Lercanidipine and its enantiomers inhibited the replication and migration of arterial myocytes in concentrations ranging from 10 to 50 microM. The antiproliferative effect of lercanidipine was dose dependent, with a potency similar to that of lacidipine and nifedipine, and was unrelated to the stereoselectivity of enantiomers to bind L-type calcium channels. Lercanidipine and its enantiomers (25 microM) decreased the serum-induced elevation of [Ca2+]i in SMC, with the (S)-enantiomer (69% inhibition) being 2.4-fold more active than the (R)-counterpart (29% inhibition). The studies performed with enantiomers of lercanidipine suggest that the observed effects are not related to the blockade of voltage-dependent Ca2+ channels and confirm, at least in vitro, the pharmacological potential of the compound to influence negatively the process of atherogenesis. FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Accomazzo, M R AU - Accomazzo MR FAU - Canavesi, M AU - Canavesi M FAU - Sartani, A AU - Sartani A FAU - Testa, R AU - Testa R FAU - Catapano, A L AU - Catapano AL FAU - Fumagalli, R AU - Fumagalli R FAU - Paoletti, R AU - Paoletti R FAU - Bernini, F AU - Bernini F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Sweden TA - Blood Press Suppl JT - Blood pressure. Supplement JID - 9300787 RN - 0 (Antihypertensive Agents) RN - 0 (Calcium Channel Blockers) RN - 0 (Dihydropyridines) RN - 9B627AW319 (Nitrendipine) RN - V7XTJ4R0BH (lercanidipine) SB - IM MH - Animals MH - Antihypertensive Agents/chemistry/*pharmacology MH - Arteriosclerosis/metabolism/*prevention & control MH - Brain/drug effects/metabolism MH - Calcium Channel Blockers/chemistry/*pharmacology MH - Cell Division/drug effects MH - Dihydropyridines/chemistry/*pharmacology MH - In Vitro Techniques MH - Male MH - Membranes/drug effects/metabolism MH - Muscle, Smooth, Vascular/drug effects/pathology MH - Nitrendipine/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Stereoisomerism EDAT- 1998/12/16 00:00 MHDA- 1998/12/16 00:01 CRDT- 1998/12/16 00:00 PHST- 1998/12/16 00:00 [pubmed] PHST- 1998/12/16 00:01 [medline] PHST- 1998/12/16 00:00 [entrez] PST - ppublish SO - Blood Press Suppl. 1998;2:18-22. PMID- 9267705 OWN - NLM STAT- MEDLINE DCOM- 19970929 LR - 20061115 IS - 0009-8981 (Print) IS - 0009-8981 (Linking) VI - 264 IP - 1 DP - 1997 Aug 8 TI - A new fluorometric method for measuring the action of C apolipoproteins on milk lipoprotein lipase. PG - 75-90 AB - Monolayer vesicles containing pyrene-labelled nonanoyltriglyceride (1-2 ditetradecyl 3-pyrene nonanoyl glyceride) were used as a substrate to measure bovine milk lipoprotein lipase activity. The activation of lipoprotein lipase by synthetic fragments of apolipoprotein C II and apo C III was measured. Fragments 30-78 and 43-78 had actions similar to that of the entire apo C II. Fragments 50-78 and 55-78 were 50% active, fragment 60-78 was 10% active and fragment 66-78 was inactive. Thus the activating capacity depended on the length of the carboxyterminal fragment. Replacing tyrosine 62 in apo C II by glycine removed all lipoprotein lipase activating capacity, while making Tyr 62 less accessible for binding to lipids and enzyme decreased apo C II activating capacity. Apo C III1 inhibited both basal lipoprotein lipase activity (no apo C II) and lipoprotein lipase activated by apo C II. Apo C III, fragment A (1-40) which did not bind lipids, had no inhibitory effect, while fragment B(41-79) had the same effect as whole apo C III,. Apo AI, AII and C I also inhibited lipoprotein lipase. The fluorometric assay is easy to perform, and suitable for metabolic studies such as fatty-acid exchanges between lipoproteins, as it produces no alteration in the reaction products. It also avoids the use of a radio-labelled substrate. FAU - Lambert, D A AU - Lambert DA AD - I.N.S.E.RM. U. 308, Faculte de Medecine, Vandoeuvre, France. FAU - Catapano, A L AU - Catapano AL FAU - Smith, L C AU - Smith LC FAU - Sparrow, J T AU - Sparrow JT FAU - Gotto, A M Jr AU - Gotto AM Jr LA - eng PT - Journal Article PL - Netherlands TA - Clin Chim Acta JT - Clinica chimica acta; international journal of clinical chemistry JID - 1302422 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoprotein C-III) RN - 0 (Apolipoproteins C) RN - 0 (Milk Proteins) RN - 0 (Peptides) RN - 0 (Pyrenes) RN - 0 (Triglycerides) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Animals MH - Apolipoprotein C-II MH - Apolipoprotein C-III MH - Apolipoproteins C/metabolism/*pharmacology MH - Cattle MH - Enzyme Activation/drug effects MH - Fluorometry/*methods MH - Hydrolysis/drug effects MH - Lipoprotein Lipase/antagonists & inhibitors/isolation & purification/*metabolism MH - Milk Proteins/antagonists & inhibitors/isolation & purification/*metabolism MH - Peptides/pharmacology MH - Pyrenes MH - Triglycerides/metabolism EDAT- 1997/08/08 00:00 MHDA- 2001/03/28 10:01 CRDT- 1997/08/08 00:00 PHST- 1997/08/08 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1997/08/08 00:00 [entrez] AID - S0009898197000752 [pii] PST - ppublish SO - Clin Chim Acta. 1997 Aug 8;264(1):75-90. PMID- 9126658 OWN - NLM STAT- MEDLINE DCOM- 19970709 LR - 20181130 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 130 IP - 1-2 DP - 1997 Apr TI - Decreased intracellular degradation and increased secretion of apo B-100 in Hep G2 cells after inhibition of cholesteryl ester synthesis. PG - 143-52 AB - Control of apolipoprotein B (apo B) secretion in hepatocytes occurs partly at the post-translational level. The key step in this process appears to be intracellular degradation of newly synthesized apo B. The aim of this paper was to investigate the mechanisms that regulate apo B secretion by Hep G2 cells, in response to the inhibition of Acyl-CoA Acyltransferase (ACAT) by the compound Sandoz 58035 (S-58035). S-58035 (20 microM) reduced cholesteryl ester synthesis from [14C]oleate by 95%, and increased significantly, in a dose-dependent manner, (2-100 microM) apo B secretion, either in control conditions (from 78 +/- 4.3 to 126 +/- 6.1 ng apo B-100/mg cell protein/4 h) or upon stimulation of apo B secretion by oleate (from 134 +/- 4.23 to 177 +/- 4.3 ng apo B/mg cell protein/4 h). This increased secretion of newly synthesized apo B-100 was confirmed by pulse experiments and by gradient ultracentrifugation of the media. Moreover pulse-chase experiments showed that the addition of S-58035 reduced intracellular degradation of apo B-100, both in control conditions and in the presence of oleate. S-58035 (20 microM) did not affect total cellular cholesterol content, but free cholesterol increased with a concomitant decrease of cholesteryl ester (-20%). S-58035 increased cellular triglyceride mass, which was observed in basal conditions (from 12.8 +/- 1.09 to 22.7 +/- 2.7 micrograms TG/mg cellular protein) and also in presence of oleate (from 48 +/- 0.53 to 59 +/- 6.3 micrograms TG/mg cellular protein). This effect is due to a stimulation of triglyceride synthesis, as determined by incorporation of [3H]glycerol into cellular triglycerides. From these data we conclude that, under our experimental conditions, triglyceride synthesis and/or availability is likely to control intracellular degradation of apo B. FAU - Ooyen, C AU - Ooyen C AD - Institute of Pharmacological Sciences, Milano, Italy. FAU - Zecca, A AU - Zecca A FAU - Zanelli, T AU - Zanelli T FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Amides) RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoproteins B) RN - 0 (Cholesterol Esters) RN - 0 (Enzyme Inhibitors) RN - 0 (Organosilicon Compounds) RN - 0 (Triglycerides) RN - 2UMI9U37CP (Oleic Acid) RN - 78934-83-5 (SAN 58035) RN - EC 2.3.1.26 (Sterol O-Acyltransferase) SB - IM MH - Amides/pharmacology MH - Apolipoprotein B-100 MH - Apolipoproteins B/*metabolism MH - Cholesterol Esters/*antagonists & inhibitors/*biosynthesis MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Lipid Metabolism MH - Liver/*metabolism MH - Oleic Acid/pharmacology MH - *Organosilicon Compounds MH - Sterol O-Acyltransferase/antagonists & inhibitors MH - Triglycerides/biosynthesis MH - Tumor Cells, Cultured EDAT- 1997/04/01 00:00 MHDA- 1997/04/01 00:01 CRDT- 1997/04/01 00:00 PHST- 1997/04/01 00:00 [pubmed] PHST- 1997/04/01 00:01 [medline] PHST- 1997/04/01 00:00 [entrez] AID - S0021-9150(96)06060-1 [pii] PST - ppublish SO - Atherosclerosis. 1997 Apr;130(1-2):143-52. PMID- 9070296 OWN - NLM STAT- MEDLINE DCOM- 19970417 LR - 20171116 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 231 IP - 2 DP - 1997 Feb 13 TI - Simvastatin modulates the heat shock response and cytotoxicity mediated by oxidized LDL in cultured human endothelial smooth muscle cells. PG - 437-41 AB - Oxidized low density lipoproteins (OxLDL) are toxic to cells of the arterial wall and trigger the expression of the inducible form of hsp 70 in cultured endothelial cells (EAhy-926) and smooth muscle cells (HUVSMC). The latter response is believed to protect cells from toxicity since heat shock protein 70 (hsp70) is synthesized by cells under stress condition to protect proteins from irreversible denaturation. Simvastatin (10(-8) M to 10(-5) M), a competitive inhibitor of hydroxy methyl glutaryl coenzyme A reductase (HMG-CoA reductase), a key enzyme in cholesterol biosynthesis, enhanced the toxicity of OxLDL (300 micrograms/mL) to endothelial cells and smooth muscle cells in a dose-dependent manner, as detected by 3H-adenine release and the MTT test. In EAhy, 3H-adenine release with OxLDL was 0.419 +/- 0.048 (ratio of radioactivity released in the medium to total radioactivity) versus 0.337 +/- 0.008 of control; in the presence of simvastatin and OxLDL this value increased from 0.49 +/- 0.01 at 10(-8) M to 0.918 +/- 0.001 at 10(-5) M with simvastatin alone (10(-5) M) this value was 0.463 +/- 0.025. Furthermore simvastatin reduced in a dose-dependent manner the expression of hsp 70 triggered by OxLDL, as detected by immunoblotting. To address whether this finding was due to the effect of simvastatin on the cholesterol pathway, mevalonate (100 microM) was used to bypass the HMG-CoA reductase block. This compound completely prevented the enhancement of OxLDL toxicity by simvastatin and restored the expression of hsp70. To verify whether cholesterol synthesis was required for the induction of hsp70 by OxLDL, squalestatin I (25 nM to 100 nM), an inhibitor of squalene synthase, another key enzyme of the cholesterol pathway, was used: OxLDL toxicity and hsp70 expression were not affected by this compound. These results indicate that simvastatin increases OxLDL cytotoxicity in vitro with a concomitant decrease of hsp70 expression triggered by OxLDL and that the key step in the cholesterol synthesis responsible for these effects must be between mevalonate and squalene formation. FAU - Pirillo, A AU - Pirillo A AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Jacoviello, C AU - Jacoviello C FAU - Longoni, C AU - Longoni C FAU - Radaelli, A AU - Radaelli A FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Enzyme Inhibitors) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipoproteins, LDL) RN - 0 (Tricarboxylic Acids) RN - 0 (oxidized low density lipoprotein) RN - 1117HVX02L (squalestatin 1) RN - 9LHU78OQFD (Lovastatin) RN - AGG2FN16EV (Simvastatin) RN - EC 2.5.1.21 (Farnesyl-Diphosphate Farnesyltransferase) SB - IM MH - Bridged Bicyclo Compounds, Heterocyclic/pharmacology MH - Cell Survival/drug effects MH - Cells, Cultured MH - Endothelium, Vascular/cytology/drug effects/metabolism MH - Enzyme Inhibitors/*pharmacology MH - Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors MH - HSP70 Heat-Shock Proteins/*biosynthesis MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors MH - Lipoproteins, LDL/*metabolism MH - Lovastatin/*analogs & derivatives/pharmacology MH - Muscle, Smooth, Vascular/cytology/*drug effects/metabolism MH - Simvastatin MH - Tricarboxylic Acids/pharmacology EDAT- 1997/02/13 00:00 MHDA- 1997/02/13 00:01 CRDT- 1997/02/13 00:00 PHST- 1997/02/13 00:00 [pubmed] PHST- 1997/02/13 00:01 [medline] PHST- 1997/02/13 00:00 [entrez] AID - S0006-291X(97)96117-9 [pii] AID - 10.1006/bbrc.1997.6117 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1997 Feb 13;231(2):437-41. doi: 10.1006/bbrc.1997.6117. PMID- 8995342 OWN - NLM STAT- MEDLINE DCOM- 19970205 LR - 20170214 IS - 0003-3197 (Print) IS - 0003-3197 (Linking) VI - 48 IP - 1 DP - 1997 Jan TI - Antioxidant effect of flavonoids. PG - 39-44 AB - Our body generates hydroxyl radicals under a number of conditions. This radical is very unstable and, therefore, very reactive. After attack of radicals on membranes and lipoproteins, lipid peroxidation starts, and may lead to the development of vascular lesions. The human body has developed antioxidant defenses to protect against free radicals such as superoxide dismutases, glutathione peroxidases, plasma iron binding proteins, or alpha tocopherol. Oxidized LDL are believed to play a key role in vascular damage and can modulate several endothelial properties including NO production and expression of adhesion molecules. Antioxidants, such as flavonoids, inhibit "in vitro" oxidation of LDL and their cytotoxicity; in humans consumption of flavonoids appears to be related to a reduction of the risk of cardiovascular diseases. The biochemical mechanisms responsible for this effect remain to be addressed. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences and Centro per lo Studio, la Prevenzione e la Terapia delle Vasculopatie Aterosclerotiche, University of Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Angiology JT - Angiology JID - 0203706 RN - 0 (Antioxidants) RN - 0 (Flavonoids) RN - 0 (Lipoproteins, LDL) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase) SB - IM MH - Antioxidants/*pharmacology MH - Arachidonate 15-Lipoxygenase/physiology MH - Arteriosclerosis/physiopathology MH - Endothelium, Vascular/physiology MH - Flavonoids/*pharmacology MH - Humans MH - Lipoproteins, LDL/*metabolism MH - Nitric Oxide/biosynthesis MH - Oxidation-Reduction RF - 42 EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] AID - 10.1177/000331979704800107 [doi] PST - ppublish SO - Angiology. 1997 Jan;48(1):39-44. doi: 10.1177/000331979704800107. PMID- 9049542 OWN - NLM STAT- MEDLINE DCOM- 19970522 LR - 20131121 IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 18 Suppl A DP - 1997 Jan TI - Calcium antagonists and atherosclerosis. Experimental evidence. PG - A80-6 AB - Accumulation of cholesterol and calcium is the hallmark of atherosclerosis. Ca2+ antagonists lessen the severity of experimentally induced atherosclerosis in a variety of animal models, including hypercholesterolaemic animals. They also reduce cholesterol accumulation in the arterial wall, but without affecting plasma lipids. This review briefly discusses in vitro and in vivo experimental studies on the anti-atherosclerotic properties of Ca2+ antagonists and outlines mechanisms by which these compounds affect cellular lipid metabolism. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Calcium Channel Blockers) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Arteriosclerosis/*drug therapy/metabolism/pathology MH - Blood Vessels/drug effects/metabolism/pathology MH - Calcium Channel Blockers/*pharmacology MH - Cholesterol/metabolism MH - Humans RF - 73 EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] PST - ppublish SO - Eur Heart J. 1997 Jan;18 Suppl A:A80-6. PMID- 9125310 OWN - NLM STAT- MEDLINE DCOM- 19970421 LR - 20141120 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 127 IP - 2 DP - 1996 Dec 20 TI - Effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified milk lipoprotein lipase to hydrolyse triglycerides in monolayer vesicles. PG - 205-12 AB - The effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified bovine milk lipoprotein lipase to hydrolyse triglycerides was measured in a controlled model of pyrene-labeled nonanoyltriglycerides (1-2 ditetradecyl 3-pyrene nonanoyl glyceride) monolayer vesicles. Monolayer was composed of triglycerides, a non-hydrolysable phospholipid ether and cholesterol, a model system where the quality of the interface can be controlled. LPL released fatty acids from pyrene-triglycerides which were transferred from the lipoprotein structure to albumin. This transfer induces a decrease in the excimer production and in the excimer fluorescence intensity. Apolipoprotein C-II and C-III0 and C-III1 were purified from apolipoprotein VLDL. The 2 fragments, C-III1 A (peptide 1-40) and C-III1 B (peptide 41-79), were obtained after thrombin cleavage. Apolipoproteins C-III0 and C-III1 had a similar inhibitory effect on LPL. Inhibition with apo C-III0 or apo C-III1 was 85% of full LPL activity without inhibitor: Apo C-III1 B inhibited 62% of basal activity. It was 27% less effective than apo C-III1. Fragment C-III1 A did not inhibit LPL. The effect of change in both apo C-II (0-0.6 microM) and apo C-III1 (0-1.0 microM) on triglyceride hydrolysis shows the importance of the apo C-II/C-III1 ratio for the release of free fatty acids from triglycerides by LPL. The activating effect of apo C-II in the absence of the apo C-III inhibitor was maximal at 0.06 microM. No further activation was obtained between 0.06 and 0.30 microM. Higher concentrations decreased LPL activity. Apo C-III1 (0.1 microM) decreased the maximum activation by apo C-II from 0.0196 to 0.063 nmol/min/nmol LPL. Higher concentrations of apo C-III1 (0.1-0.5 microM) required higher apo C-II concentrations (0.30 microM instead of 0.06 microM) for maximal activation than when apo C-III1 was absent. The activity of the enzyme without apo C-II was decreased by 65% by 0.12 microM apo C-III1. Increasing the apo C-II/apo C-III1 ratio from 0.1 to 1, increased the activation of the enzyme by a given apo C-II concentration. Moreover, for a given apo C-II/C-III1 ratio, the LPL activation increased with the apo C-II concentration (between 0 and 0.010 microM), until a plateau was reached. This is important, as the change in the C-II/C-III1 ratio is not the only factor affecting LPL activity, and inhibition by apo C-III1 also depends on the overall quantity of apolipoproteins. Extrapolation of these results suggests that hyperlipoproteinemia seems to be more likely due to overproduction of VLDL, than to a decrease in lipoprotein lipase activity. FAU - Lambert, D A AU - Lambert DA AD - INSERM U. 308, Faculte de Medecine, BP 184, Vandoeuvre, France. FAU - Catapano, A L AU - Catapano AL FAU - Smith, L C AU - Smith LC FAU - Sparrow, J T AU - Sparrow JT FAU - Gotto, A M Jr AU - Gotto AM Jr LA - eng PT - Journal Article PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoprotein C-III) RN - 0 (Apolipoproteins C) RN - 0 (Chylomicrons) RN - 0 (Milk Proteins) RN - 0 (Triglycerides) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Animals MH - Apolipoprotein C-II MH - Apolipoprotein C-III MH - Apolipoproteins C/*pharmacology MH - Biological Transport MH - Cattle MH - Chylomicrons/drug effects/*physiology MH - Hydrolysis/drug effects MH - In Vitro Techniques MH - Lipoprotein Lipase/drug effects/*metabolism MH - Milk Proteins/metabolism MH - Triglycerides/*metabolism EDAT- 1996/12/20 00:00 MHDA- 2001/03/28 10:01 CRDT- 1996/12/20 00:00 PHST- 1996/12/20 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1996/12/20 00:00 [entrez] AID - S0021-9150(96)05955-2 [pii] PST - ppublish SO - Atherosclerosis. 1996 Dec 20;127(2):205-12. PMID- 9125304 OWN - NLM STAT- MEDLINE DCOM- 19970421 LR - 20061115 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 127 IP - 2 DP - 1996 Dec 20 TI - Stress proteins and atherosclerosis. PG - 147-54 AB - Several cytotoxic stimuli of a different nature are involved in the complex etiology of atherosclerosis. Cells of the vasculature may potentially cope with the presence of these stressors through the increased synthesis of stress proteins (or heat shock proteins, hsps), an ubiquitous and conserved defense response. Evidence exists that the expression of two stress proteins of intermediate molecular weight, hsp60 and hsp70, is higher at sites of atherosclerotic lesions than it is in normal tissue. The role of hsps in atherosclerosis is controversial. While hsp70 is likely to be involved in cytoprotection, hsp60 is probably acting as an autoantigen, and may trigger both cell-mediated and antibody-mediated immune responses. FAU - Roma, P AU - Roma P AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Chaperonin 60) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Heat-Shock Proteins) SB - IM MH - Animals MH - *Arteriosclerosis/etiology/immunology/metabolism MH - Chaperonin 60/physiology MH - HSP70 Heat-Shock Proteins/physiology MH - Heat-Shock Proteins/*physiology MH - Humans MH - Risk Factors RF - 97 EDAT- 1996/12/20 00:00 MHDA- 1996/12/20 00:01 CRDT- 1996/12/20 00:00 PHST- 1996/12/20 00:00 [pubmed] PHST- 1996/12/20 00:01 [medline] PHST- 1996/12/20 00:00 [entrez] AID - S0021-9150(96)05952-7 [pii] PST - ppublish SO - Atherosclerosis. 1996 Dec 20;127(2):147-54. PMID- 9017508 OWN - NLM STAT- MEDLINE DCOM- 19970902 LR - 20061115 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 37 IP - 12 DP - 1996 Dec TI - Localization of apolipoprotein A-I epitopes involved in the activation of lecithin:cholesterol acyltransferase. PG - 2557-68 AB - Eight murine monoclonal antibodies (Mab) to apolipoprotein A-I were characterized for their epitopes and for their ability to interfere with lecithin:cholesterol acyltransferase (LCAT) activation mediated by apo apoA-I using a synthetic substrate. Using overlapping synthetic peptides we have identified six continuous epitopes that span amino acids 1-10 (Mab A-I-19), 96-101 (Mab A-I-15), 133-141 (Mab A-I-5), 140-145 (Mab A-I-9), 144-148 (Mab A-I-8), and 167-174 (Mab A-I-57). Furthermore, antibodies A-I-11 and A-I-16 recognized discontinuous epitopes, namely amino acids 124-128 and 144-148. When antibodies were tested for their ability to inhibit LCAT activation, an inhibitory effect was observed with those whose epitopes covered the area of apoA-I encompassing amino acids 96-174. From these data we conclude that several areas of apoA-I spanning the middle region of the apolipoprotein act in concert to stimulate LCAT activity, possibly by cooperative interaction with the enzyme. FAU - Uboldi, P AU - Uboldi P AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Spoladore, M AU - Spoladore M FAU - Fantappie, S AU - Fantappie S FAU - Marcovina, S AU - Marcovina S FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Apolipoprotein A-I) RN - 0 (Epitopes) RN - EC 2.3.1.43 (Phosphatidylcholine-Sterol O-Acyltransferase) SB - IM MH - Animals MH - Apolipoprotein A-I/*immunology/metabolism MH - Binding Sites/immunology MH - Enzyme Activation/immunology MH - Epitope Mapping MH - Epitopes/*immunology MH - Humans MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Phosphatidylcholine-Sterol O-Acyltransferase/*metabolism EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1996 Dec;37(12):2557-68. PMID- 8792763 OWN - NLM STAT- MEDLINE DCOM- 19961024 LR - 20061115 IS - 1079-5642 (Print) IS - 1079-5642 (Linking) VI - 16 IP - 9 DP - 1996 Sep TI - Human endothelial cells exposed to oxidized LDL express hsp70 only when proliferating. PG - 1104-11 AB - Oxidized LDL (OxLDL), a causal factor in atherosclerosis, is cytotoxic and triggers the expression of various heat shock proteins (hsps), among which is hsp70, in cultured animal and human cells. hsps constitutively act as molecular chaperones and in situations of stress protect other cellular proteins from potential denaturation caused by cytotoxic stimuli. The sensitivity of endothelial cells to OxLDL toxicity and accordingly the level of hsp70 expression depend on cell density. While confluent cells were relatively resistant to OxLDL toxicity and were not induced to express hsp70 when challenged with the lipoprotein (up to 800 micrograms/mL), sparse cells exhibited a concentration- and time-dependent expression of inducible hsp70, which increased up to fivefold to sixfold in unchallenged cells. Neither the activity of receptors recognizing OxLDL nor potentially protective cell products affected the stress response. Rather, we demonstrated that cell proliferation, which is high for sparse cultures and wound-healing monolayers, is responsible for these observations. We also demonstrated that the lipid moiety of OxLDL essentially accounts for the hsp-inducing effect of the lipoprotein. OxLDL has been detected in atherosclerotic lesions, which also show an increase of immunoreactive hsp72/73. We speculate that, in vivo, rapidly growing cells, such as those of lesion-prone areas, are more sensitive to the toxicity of OxLDL than are quiescent cells and that an increased expression of hsp70 may allow proliferating cells an increased chance of survival. FAU - Zhu, W AU - Zhu W AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Roma, P AU - Roma P FAU - Pirillo, A AU - Pirillo A FAU - Pellegatta, F AU - Pellegatta F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Lipoproteins, LDL) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Cell Division/drug effects MH - Cells, Cultured MH - Endothelium, Vascular/*metabolism MH - HSP70 Heat-Shock Proteins/*biosynthesis MH - Humans MH - Lipid Peroxidation MH - Lipoproteins, LDL/metabolism/*pharmacology EDAT- 1996/09/01 00:00 MHDA- 1996/09/01 00:01 CRDT- 1996/09/01 00:00 PHST- 1996/09/01 00:00 [pubmed] PHST- 1996/09/01 00:01 [medline] PHST- 1996/09/01 00:00 [entrez] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 1996 Sep;16(9):1104-11. PMID- 8735617 OWN - NLM STAT- MEDLINE DCOM- 19961016 LR - 20181113 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 118 IP - 2 DP - 1996 May TI - Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits. PG - 215-9 AB - 1. The in vivo antiatherogenic activity of the calcium antagonist, lacidipine, was investigated in two different types of atherosclerotic lesions (proliferative and fatty lesions) induced in rabbits. 2. The proliferative lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty lesions were induced by cholesterol feeding. Cholesterol (1%) and lacidipine (1, 3, and 10 mg kg-1) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative lesion) was induced 6 weeks after dietary and drug treatment started. 3. The neointimal formation was determined by measuring cross sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals (n = 5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries with no collar (sham) showed an I/M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.62 +/- 0.12. In lacidipine-treated animals a significant and dose-dependent effect on proliferative lesions at all three doses tested, was observed. I/M ratios were 0.47 +/- 0.02, 0.40 +/- 0.09, 0.32 +/- 0.02 for doses 1, 3, and 10 mg kg-1 day-1, respectively (P < 0.05). 4. The fatty lesion extent was significantly reduced by lacidipine at the 10 mg kg-1 day-1 dose, although a trend was also observed with lower dosage. 5. These results suggest a direct antiatherosclerotic effect of lacidipine, independent of modulation of risk factors such as hypercholesterolaemia and/or hypertension. Furthermore, the proliferative lesions are apparently more sensitive to lacidipine than are lipid-rich lesions. FAU - Soma, M R AU - Soma MR AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Donetti, E AU - Donetti E FAU - Seregni, R AU - Seregni R FAU - Barberi, L AU - Barberi L FAU - Fumagalli, R AU - Fumagalli R FAU - Paoletti, R AU - Paoletti R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Calcium Channel Blockers) RN - 0 (Dihydropyridines) RN - 0 (Lipids) RN - 260080034N (lacidipine) SB - IM MH - Animals MH - Aorta/drug effects/pathology MH - Arteriosclerosis/*prevention & control MH - Calcium Channel Blockers/pharmacology/*therapeutic use MH - Dihydropyridines/pharmacology/*therapeutic use MH - Hypercholesterolemia/blood/*drug therapy MH - Hyperplasia MH - Lipids/blood MH - Male MH - Rabbits PMC - PMC1909615 EDAT- 1996/05/01 00:00 MHDA- 1996/05/01 00:01 CRDT- 1996/05/01 00:00 PHST- 1996/05/01 00:00 [pubmed] PHST- 1996/05/01 00:01 [medline] PHST- 1996/05/01 00:00 [entrez] PST - ppublish SO - Br J Pharmacol. 1996 May;118(2):215-9. PMID- 7556627 OWN - NLM STAT- MEDLINE DCOM- 19951106 LR - 20131121 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 372 IP - 1 DP - 1995 Sep 18 TI - Oxidized LDL induce hsp70 expression in human smooth muscle cells. PG - 1-5 AB - Heat shock protein 70 (hsp70) has been detected in atherosclerotic lesions, in which endothelial cells and smooth muscle cells are involved. In a previous report we showed that Ox-LDL, a causal factor in atherosclerosis, could induce hsp70 expression in cultured human endothelial cells [Zhu et al. B.B.R.C. 1994, 200:389]. Here, with immunofluorescence and immunoblotting techniques, we show that Ox-LDL are capable of inducing hsp70 expression also in human smooth muscle cells, and that this induction is dependent on cell density and on the concentration of Ox-LDL. The induced expression of hsp70 was higher in human umbilical vein smooth muscle cells than in a human smooth muscle cell line. Conversely, Ox-LDL was cytotoxic to both types of cells, more so to the human smooth muscle cell line. These observations indicate that Ox-LDL may be a stress responsible for hsp70 expression in atherosclerotic plaques and the presence of hsp70 in plaques may be a useful marker for continuous oxidative damage in the arterial wall. FAU - Zhu, W M AU - Zhu WM AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Roma, P AU - Roma P FAU - Pirillo, A AU - Pirillo A FAU - Pellegatta, F AU - Pellegatta F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (Actins) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Lipoproteins, LDL) RN - 0 (acetyl-LDL) RN - 98600C0908 (Cycloheximide) SB - IM MH - Actins/analysis MH - Cell Count MH - Cell Division MH - Cell Line MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cycloheximide/pharmacology MH - Female MH - Fluorescent Antibody Technique MH - HSP70 Heat-Shock Proteins/*biosynthesis MH - Humans MH - Immunoblotting MH - Lipoproteins, LDL/*pharmacology MH - Muscle, Smooth, Vascular/cytology/drug effects/*metabolism MH - Oxidation-Reduction MH - Umbilical Veins EDAT- 1995/09/18 00:00 MHDA- 1995/09/18 00:01 CRDT- 1995/09/18 00:00 PHST- 1995/09/18 00:00 [pubmed] PHST- 1995/09/18 00:01 [medline] PHST- 1995/09/18 00:00 [entrez] AID - 0014-5793(95)00834-V [pii] PST - ppublish SO - FEBS Lett. 1995 Sep 18;372(1):1-5. PMID- 7784310 OWN - NLM STAT- MEDLINE DCOM- 19950714 LR - 20150831 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 31 IP - 1 DP - 1995 Jan TI - Pharmacology of competitive inhibitors of HMG-CoA reductase. PG - 9-27 FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Maggi, F M AU - Maggi FM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anticholesteremic Agents) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 97C5T2UQ7J (Cholesterol) RN - 9LHU78OQFD (Lovastatin) RN - AGG2FN16EV (Simvastatin) RN - S5UOB36OCZ (Mevalonic Acid) SB - IM MH - Animals MH - Anticholesteremic Agents/*pharmacology MH - Arteriosclerosis/metabolism/prevention & control MH - Cattle MH - Cells, Cultured/drug effects MH - Chick Embryo MH - Cholesterol/*biosynthesis/blood MH - Cricetinae MH - Dogs MH - Guinea Pigs MH - Humans MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors MH - Lipid Metabolism MH - Lipids/blood MH - Lipoproteins/drug effects MH - Lovastatin/analogs & derivatives/pharmacology MH - Mevalonic Acid/metabolism MH - Mice MH - Organ Specificity MH - Rabbits MH - Rats MH - Simvastatin RF - 211 EDAT- 1995/01/01 00:00 MHDA- 1995/01/01 00:01 CRDT- 1995/01/01 00:00 PHST- 1995/01/01 00:00 [pubmed] PHST- 1995/01/01 00:01 [medline] PHST- 1995/01/01 00:00 [entrez] AID - 1043-6618(95)80042-5 [pii] PST - ppublish SO - Pharmacol Res. 1995 Jan;31(1):9-27. PMID- 7515687 OWN - NLM STAT- MEDLINE DCOM- 19940708 LR - 20131121 IS - 0006-2960 (Print) IS - 0006-2960 (Linking) VI - 33 IP - 22 DP - 1994 Jun 7 TI - Unique epitope of apolipoprotein A-I expressed in pre-beta-1 high-density lipoprotein and its role in the catalyzed efflux of cellular cholesterol. PG - 6981-5 AB - The ability of mouse anti-apolipoprotein A-I (apo A-I) monoclonal antibodies to recognize pre-beta-HDL species in native plasma was determined. An antibody identifying residues 137-144 of the mature protein uniquely recognized pre-beta-1 HDL, an HDL species of low molecular weight implicated in early cholesterol transport from cell membranes to plasma [Castro, G. R., & Fielding, C. J. (1988) Biochemistry 27, 25-29]. Incubation of plasma with this antibody significantly inhibited the efflux of labeled cholesterol from cultured fibroblast monolayers. A second antibody, binding to residues 93-99 of apo A-I, recognized a second pre-beta-HDL species (pre-beta-2 HDL) but not pre-beta-1 HDL and did not inhibit cholesterol efflux. Several other antibodies had broad specificity for HDL (including pre-beta-1 HDL). This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-beta-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species. FAU - Fielding, P E AU - Fielding PE AD - Cardiovascular Research Institute, University of California, San Francisco 94143-0130. FAU - Kawano, M AU - Kawano M FAU - Catapano, A L AU - Catapano AL FAU - Zoppo, A AU - Zoppo A FAU - Marcovina, S AU - Marcovina S FAU - Fielding, C J AU - Fielding CJ LA - eng GR - HL 14237/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biochemistry JT - Biochemistry JID - 0370623 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein A-I) RN - 0 (Epitopes) RN - 0 (High-Density Lipoproteins, Pre-beta) RN - 0 (Lipoproteins, HDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Amino Acid Sequence MH - Antibodies, Monoclonal MH - Apolipoprotein A-I/*chemistry/immunology MH - Catalysis MH - Cells, Cultured MH - Cholesterol/*metabolism MH - Epitopes/analysis MH - Fibroblasts/metabolism MH - High-Density Lipoproteins, Pre-beta MH - Humans MH - Lipoproteins, HDL/*chemistry/immunology/*physiology MH - Molecular Sequence Data EDAT- 1994/06/07 00:00 MHDA- 1994/06/07 00:01 CRDT- 1994/06/07 00:00 PHST- 1994/06/07 00:00 [pubmed] PHST- 1994/06/07 00:01 [medline] PHST- 1994/06/07 00:00 [entrez] PST - ppublish SO - Biochemistry. 1994 Jun 7;33(22):6981-5. PMID- 7514253 OWN - NLM STAT- MEDLINE DCOM- 19940616 LR - 20170920 IS - 0140-6736 (Print) IS - 0140-6736 (Linking) VI - 343 IP - 8908 DP - 1994 May 21 TI - Protection of low-density lipoprotein from oxidation by 3,4-dihydroxyphenylethanol. PG - 1296-7 FAU - Grignaffini, P AU - Grignaffini P FAU - Roma, P AU - Roma P FAU - Galli, C AU - Galli C FAU - Catapano, A L AU - Catapano AL LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Antioxidants) RN - 0 (Lipoproteins, LDL) RN - 10597-60-1 (3,4-dihydroxyphenylethanol) RN - ML9LGA7468 (Phenylethyl Alcohol) SB - AIM SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Humans MH - Lipoproteins, LDL/*chemistry MH - Oxidation-Reduction MH - Phenylethyl Alcohol/*analogs & derivatives/pharmacology MH - Rabbits EDAT- 1994/05/21 00:00 MHDA- 1994/05/21 00:01 CRDT- 1994/05/21 00:00 PHST- 1994/05/21 00:00 [pubmed] PHST- 1994/05/21 00:01 [medline] PHST- 1994/05/21 00:00 [entrez] AID - S0140-6736(94)92186-5 [pii] PST - ppublish SO - Lancet. 1994 May 21;343(8908):1296-7. PMID- 8166710 OWN - NLM STAT- MEDLINE DCOM- 19940523 LR - 20171116 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 200 IP - 1 DP - 1994 Apr 15 TI - Oxidized-LDL induce the expression of heat shock protein 70 in human endothelial cells. PG - 389-94 AB - Heat shock proteins are detectable in human atherosclerotic plaques, especially in endothelial cells. In this report we show by immunofluorescence that incubation "in vitro" with OxLDL is a stress capable of inducing the expression of heat shock protein 70 in both the EAhy-926 cell line and human umbilical vein endothelial cells (HUVEC). This induction was parallel to the cytotoxicity of oxidized LDL as determined by [3H]adenine release. When cells were confluent, however, both effects were greatly reduced. We speculate that induction of hsp70 is related to the cytotoxicity of oxidized LDL and that the detection of heat shock proteins in human atherosclerotic plaques is a further indication for the presence "in vivo" of oxidized LDL. These observations may be relevant to the understanding of endothelial response to injury in proatherosclerotic events. FAU - Zhu, W AU - Zhu W AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Roma, P AU - Roma P FAU - Pellegatta, F AU - Pellegatta F FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Heat-Shock Proteins) RN - 0 (Lipoproteins, LDL) RN - 10028-17-8 (Tritium) RN - 27432CM55Q (Serum Albumin, Bovine) RN - JAC85A2161 (Adenine) SB - IM MH - Adenine/metabolism MH - Cell Count MH - Cells, Cultured MH - Endothelium, Vascular/cytology/drug effects/*metabolism MH - Heat-Shock Proteins/*biosynthesis MH - Humans MH - Hybrid Cells MH - Kinetics MH - Lipoproteins, LDL/*pharmacology MH - Lung Neoplasms MH - Serum Albumin, Bovine/pharmacology MH - Tritium MH - Tumor Cells, Cultured MH - Umbilical Veins EDAT- 1994/04/15 00:00 MHDA- 1994/04/15 00:01 CRDT- 1994/04/15 00:00 PHST- 1994/04/15 00:00 [pubmed] PHST- 1994/04/15 00:01 [medline] PHST- 1994/04/15 00:00 [entrez] AID - S0006-291X(84)71461-6 [pii] AID - 10.1006/bbrc.1994.1461 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1994 Apr 15;200(1):389-94. doi: 10.1006/bbrc.1994.1461. PMID- 8004780 OWN - NLM STAT- MEDLINE DCOM- 19940715 LR - 20131121 IS - 0009-8981 (Print) IS - 0009-8981 (Linking) VI - 224 IP - 2 DP - 1994 Jan 31 TI - A new case of apo C-II deficiency with a nonsense mutation in the apo C-II gene. PG - 111-8 AB - The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction (PCR). The sequence analysis revealed a substitution of adenosine for cytosine at position 3,002 in exon 3, leading to the introduction of a premature stop codon (TAA) at a position corresponding to aminoacid 37 of mature apo C-II. This mutation creates a new Rsa I restriction enzyme site in the apo C-II gene. Amplification of DNA from family members by PCR and digestion with Rsa I established that the patient is a true homozygote for this mutation. The same nucleotide has been substituted for the mutation apo C-IIPadova and apo C-IIBari previously described in two kindreds from Italy. From these data we speculate that base pair 3,002 in the apo C-II gene may represent a hot spot for mutation. FAU - Zanelli, T AU - Zanelli T AD - Istituto di Scienze Farmacologiche, Universita di Milano, Italy. FAU - Catapano, A L AU - Catapano AL FAU - Averna, M R AU - Averna MR FAU - Barbagallo, C M AU - Barbagallo CM FAU - Liotta, A AU - Liotta A FAU - Giardina, F C AU - Giardina FC FAU - Notarbartolo, A AU - Notarbartolo A LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Clin Chim Acta JT - Clinica chimica acta; international journal of clinical chemistry JID - 1302422 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoproteins C) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Apolipoprotein C-II MH - Apolipoproteins C/*deficiency/*genetics MH - Base Sequence MH - Child, Preschool MH - Cholesterol/blood MH - Exons/physiology MH - Humans MH - Hyperlipoproteinemia Type II/genetics MH - Isoelectric Focusing MH - Lipoprotein Lipase/blood MH - Male MH - Molecular Sequence Data MH - Mutation MH - Polymerase Chain Reaction MH - Sequence Analysis, DNA MH - Triglycerides/blood EDAT- 1994/01/31 00:00 MHDA- 1994/01/31 00:01 CRDT- 1994/01/31 00:00 PHST- 1994/01/31 00:00 [pubmed] PHST- 1994/01/31 00:01 [medline] PHST- 1994/01/31 00:00 [entrez] AID - 0009-8981(94)90176-7 [pii] PST - ppublish SO - Clin Chim Acta. 1994 Jan 31;224(2):111-8. PMID- 7609512 OWN - NLM STAT- MEDLINE DCOM- 19950817 LR - 20141120 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 23 Suppl 5 DP - 1994 TI - Effect of lacidipine on the carotid intimal hyperplasia induced by cuff injury. PG - S71-4 AB - The in vivo antiatherogenic activity of the calcium antagonist lacidipine was investigated in arterial hyperplasia induced by perivascular manipulation of hypercholesterolemic carotid rabbits. This was accomplished by positioning a hollow silastic collar around one carotid, which within a few days induces an atherosclerotic lesion (proliferative lesion) showing biochemical and morphologic changes similar to those of early human atherosclerosis: the contralateral carotid, with no collar, served as control in the same animal. The effect of lacidipine was also investigated in aortic atherosclerotic lesions (fatty lesions) induced by hypercholesterolemia mixed with either cholesterol (1%) and lacidipine (3 mg/kg/day) or cholesterol (1%) alone for 8 weeks. Hypercholesterolemic New Zealand White rabbits were fed daily a standard diet. Intimal hyperplasia was mechanically induced in one carotid artery of each rabbit 6 weeks after dietary and drug treatment started. Neointimal formation was followed by measuring by light microscopy the cross-sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In positive control animals receiving dietary cholesterol only (n = 10), by 14 d after collar positioning the process of intimal hyperplasia was significantly pronounced. The control arteries showed an I:M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.56 +/- 0.11. In the animals receiving lacidipine, neointimal formation was significantly lower [I:M tissue ratio 0.32 +/- 0.1 (n = 10), about 60% of positive controls]. Measurement of the percent area of the aortic intima covered by plaques did not show significant differences between control and lacidipine-treated animals. These results suggest a direct antiatherosclerotic effect of lacidipine on proliferative lesions. FAU - Soma, M R AU - Soma MR AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Donetti, E AU - Donetti E FAU - Parolini, C AU - Parolini C FAU - Barberi, L AU - Barberi L FAU - Paoletti, R AU - Paoletti R FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Calcium Channel Blockers) RN - 0 (Dihydropyridines) RN - 260080034N (lacidipine) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Aorta/pathology MH - Aorta, Thoracic/pathology MH - Arteriosclerosis/drug therapy/pathology MH - Calcium Channel Blockers/*therapeutic use MH - Carotid Arteries/drug effects/*pathology MH - Carotid Artery Injuries MH - Cholesterol/blood MH - Diet, Atherogenic MH - Dihydropyridines/*therapeutic use MH - Hyperplasia/pathology/prevention & control MH - Male MH - Rabbits EDAT- 1994/01/01 00:00 MHDA- 1994/01/01 00:01 CRDT- 1994/01/01 00:00 PHST- 1994/01/01 00:00 [pubmed] PHST- 1994/01/01 00:01 [medline] PHST- 1994/01/01 00:00 [entrez] PST - ppublish SO - J Cardiovasc Pharmacol. 1994;23 Suppl 5:S71-4. PMID- 8108312 OWN - NLM STAT- MEDLINE DCOM- 19940324 LR - 20150831 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 28 IP - 3 DP - 1993 Oct-Nov TI - SIM 6080, a new calcium antagonist, reduces aortic atherosclerosis in cholesterol-fed rabbits. PG - 219-27 AB - SIM 6080 is a new calcium antagonist, structurally related to diphenylalkylamines, which combines transmembrane and intracellular calcium antagonist activities. In the present study we investigated the effect of SIM 6080 on atherogenesis in cholesterol-fed rabbits. Subcutaneous administration of the compound at 0.33, 1, and 3 mg kg-1/bid for 60 days neither affected plasma lipids nor blood pressure. However at 1 and 3 mg kg-1/bid SIM 6080 reduced in a dose-dependent manner both the area of the aorta covered by plaques and aortic cholesterol content. Determination of SIM 6080 plasma and aortic content indicated that the compound could concentrate up to 10 times in the arterial tissue. In vitro studies demonstrated that at concentrations similar to those observed in the aorta this compound may stimulate rabbit beta VLDL catabolism by smooth muscle cells in an homologous system suggesting that the up-regulation of LDL-receptors in the aorta may contribute to the antiatherosclerotic properties of SIM 6080. FAU - Maggi, F M AU - Maggi FM AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Bernini, F AU - Bernini F FAU - Barberi, L AU - Barberi L FAU - Fantoni, M AU - Fantoni M FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Calcium Channel Blockers) RN - 0 (Cholesterol, Dietary) RN - 0 (Ethylenediamines) RN - 0 (Lipids) RN - 0 (Lipoproteins, VLDL) RN - 118790-68-4 (SIM 6080) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Aorta, Thoracic/drug effects/metabolism/pathology MH - Arteriosclerosis/*drug therapy/pathology MH - Calcium Channel Blockers/blood/*therapeutic use MH - Cells, Cultured MH - Cholesterol/metabolism MH - Cholesterol, Dietary/*pharmacology MH - *Diet, Atherogenic MH - Ethylenediamines/blood/*therapeutic use MH - Lipids/blood MH - Lipoproteins, VLDL/blood MH - Male MH - Muscle, Smooth, Vascular/drug effects/metabolism MH - Rabbits EDAT- 1993/10/01 00:00 MHDA- 1993/10/01 00:01 CRDT- 1993/10/01 00:00 PHST- 1993/10/01 00:00 [pubmed] PHST- 1993/10/01 00:01 [medline] PHST- 1993/10/01 00:00 [entrez] AID - S1043-6618(83)71125-4 [pii] AID - 10.1006/phrs.1993.1125 [doi] PST - ppublish SO - Pharmacol Res. 1993 Oct-Nov;28(3):219-27. doi: 10.1006/phrs.1993.1125. PMID- 7692863 OWN - NLM STAT- MEDLINE DCOM- 19931115 LR - 20061115 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 101 IP - 1 DP - 1993 Jun TI - Immunoreactivity of apo B towards monoclonal antibodies that inhibit the LDL-receptor interaction: effects of LDL oxidation. PG - 37-41 AB - We studied the immunochemical stability of the epitopes for six monoclonal antibodies to human apolipoprotein B-100 upon Cu(2+)-mediated (20 microM) oxidation of LDL. The antibodies used in this study, some of which are known to interfere with the interaction of LDL with their cellular receptors, recognize epitopes in the amino terminal region (Mb 19), in the middle part (6B, 2A, 7A, and 9A) and near aa 3500 (Mb 47) of native apo B. All antibodies except one (7A) recognized native and oxidized LDL (OxLDL) equally well; the immunoreactivity of the epitope for Ab 7A was markedly reduced upon LDL oxidation. Since antibodies 2A, 7A, 9A, and Mb 47 inhibit the LDL-receptor interaction and OxLDL poorly interact in vitro with the LDL receptor we conclude that: (1) various epitopes for monoclonal antibodies against native apo B are spared upon LDL oxidation; and (2) the epitopes for antibodies 2A, 9A, and Mb 47 do not define a unique domain of apo B directly involved in the binding of LDL to their receptor. FAU - Negri, S AU - Negri S AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Roma, P AU - Roma P FAU - Fogliatto, R AU - Fogliatto R FAU - Uboldi, P AU - Uboldi P FAU - Marcovina, S AU - Marcovina S FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoproteins B) RN - 0 (Epitopes) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) SB - IM MH - Antibodies, Monoclonal/*immunology MH - Antigen-Antibody Reactions MH - Apolipoproteins B/*immunology MH - Binding, Competitive MH - Epitopes MH - Fibroblasts/metabolism MH - Humans MH - Lipoproteins, LDL/*metabolism MH - Oxidation-Reduction MH - Receptors, LDL/*immunology EDAT- 1993/06/01 00:00 MHDA- 1993/06/01 00:01 CRDT- 1993/06/01 00:00 PHST- 1993/06/01 00:00 [pubmed] PHST- 1993/06/01 00:01 [medline] PHST- 1993/06/01 00:00 [entrez] AID - 0021-9150(93)90099-G [pii] PST - ppublish SO - Atherosclerosis. 1993 Jun;101(1):37-41. PMID- 8318058 OWN - NLM STAT- MEDLINE DCOM- 19930728 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 100 IP - 1 DP - 1993 Apr TI - Reduction of Lp(a) plasma levels by bezafibrate. PG - 127-8 FAU - Maggi, F M AU - Maggi FM FAU - Biasi, G M AU - Biasi GM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Letter PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoprotein(a)) RN - Y9449Q51XH (Bezafibrate) SB - IM MH - Bezafibrate/*therapeutic use MH - Humans MH - Hyperlipoproteinemias/blood/*drug therapy MH - Lipoprotein(a)/*blood EDAT- 1993/04/01 00:00 MHDA- 1993/04/01 00:01 CRDT- 1993/04/01 00:00 PHST- 1993/04/01 00:00 [pubmed] PHST- 1993/04/01 00:01 [medline] PHST- 1993/04/01 00:00 [entrez] AID - 0021-9150(93)90075-6 [pii] PST - ppublish SO - Atherosclerosis. 1993 Apr;100(1):127-8. PMID- 1294939 OWN - NLM STAT- MEDLINE DCOM- 19930412 LR - 20150831 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 26 IP - 4 DP - 1992 Dec TI - Mode of action of fibrates. PG - 331-40 AB - Fibrates are a class of hypolipidaemic drugs that effectively reduce plasma triglyceride and cholesterol levels, but also raise HDL cholesterol. In recent years the attention of pharmacologists and clinicians to fibrates has been renewed also in the light of a multifaceted action on plasma lipids as well as on factors modulating the thrombotic homeostasis in blood. The mechanisms of actions underlying these effects are discussed in this short review. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Hypolipidemic Agents) RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 53PF01Q249 (Clofibric Acid) SB - IM MH - Animals MH - Clofibric Acid/*analogs & derivatives/*pharmacology MH - Humans MH - Hypolipidemic Agents/*pharmacology MH - Lipids/blood MH - Lipoproteins/blood RF - 71 EDAT- 1992/12/01 00:00 MHDA- 1992/12/01 00:01 CRDT- 1992/12/01 00:00 PHST- 1992/12/01 00:00 [pubmed] PHST- 1992/12/01 00:01 [medline] PHST- 1992/12/01 00:00 [entrez] AID - 1043-6618(92)90232-Z [pii] PST - ppublish SO - Pharmacol Res. 1992 Dec;26(4):331-40. PMID- 1468120 OWN - NLM STAT- MEDLINE DCOM- 19930128 LR - 20171223 IS - 0009-3084 (Print) IS - 0009-3084 (Linking) VI - 62 IP - 3 DP - 1992 Oct TI - Evidence for the presence of 7-hydroperoxycholest-5-en-3 beta-ol in oxidized human LDL. PG - 209-14 AB - Low density lipoprotein (LDL) cholesterol is known to be oxidized both in vitro and in vivo giving rise to oxygenated sterols. Conflicting results, however, have been reported concerning both the nature and the relative concentrations of these compounds in oxidized human LDL. We examined the extracts obtained from Cu(2+)-oxidized LDL. Thin layer chromatography analysis showed that the sterol mixture became more complex with reaction time. Analysis of the components by thin layer chromatography and mass spectrometry allowed to establish that 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha OOH and beta OOH) are largely prevalent among the oxysterols at early times of oxidation. These hydroperoxy derivatives have not been previously identified in oxidized LDL. The concentration of 7-hydroperoxycholest-5-en-3 beta-ol decreased with oxidation time with a concomitant increase of cholest-5-en-3 beta, 7 alpha-diol (7 alpha OH), cholest-5-en-3 beta, 7 beta-diol (7 beta OH), cholesta-3,5-dien-7-one (CD) and cholest-5-en-3 beta-ol-7-one (7CO). After 24 h of oxidation a minor component of the LDL sterols was cholestan-3 beta-ol-5,6-oxide (EP). FAU - Malavasi, B AU - Malavasi B AD - Institute of Pharmacological Sciences, School of Pharmacy, University of Milan, Italy. FAU - Rasetti, M F AU - Rasetti MF FAU - Roma, P AU - Roma P FAU - Fogliatto, R AU - Fogliatto R FAU - Allevi, P AU - Allevi P FAU - Catapano, A L AU - Catapano AL FAU - Galli, G AU - Galli G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Chem Phys Lipids JT - Chemistry and physics of lipids JID - 0067206 RN - 0 (Lipoproteins, LDL) RN - 0 (Sterols) RN - 2846-29-9 (cholesterol 7-hydroperoxide) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cholesterol/*analogs & derivatives/analysis MH - Chromatography, Thin Layer MH - Gas Chromatography-Mass Spectrometry MH - Humans MH - Lipoproteins, LDL/*blood/chemistry/isolation & purification MH - Oxidation-Reduction MH - Sterols/*analysis/isolation & purification EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:01 CRDT- 1992/10/01 00:00 PHST- 1992/10/01 00:00 [pubmed] PHST- 1992/10/01 00:01 [medline] PHST- 1992/10/01 00:00 [entrez] AID - 0009-3084(92)90057-V [pii] PST - ppublish SO - Chem Phys Lipids. 1992 Oct;62(3):209-14. PMID- 1279088 OWN - NLM STAT- MEDLINE DCOM- 19921202 LR - 20061115 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 33 IP - 8 DP - 1992 Aug TI - Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction. PG - 1111-21 AB - We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor. FAU - Fantappie, S AU - Fantappie S AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Corsini, A AU - Corsini A FAU - Sidoli, A AU - Sidoli A FAU - Uboldi, P AU - Uboldi P FAU - Granata, A AU - Granata A FAU - Zanelli, T AU - Zanelli T FAU - Rossi, P AU - Rossi P FAU - Marcovina, S AU - Marcovina S FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoprotein B-48) RN - 0 (Apolipoproteins B) RN - 0 (Epitopes) RN - 0 (Fibrinolytic Agents) RN - 0 (Immunoglobulin Fab Fragments) RN - 0 (Peptide Fragments) RN - 0 (Receptors, LDL) RN - 0 (Recombinant Fusion Proteins) RN - EC 3.2.1.23 (beta-Galactosidase) SB - IM MH - Antibodies, Monoclonal MH - Apolipoprotein B-100 MH - Apolipoprotein B-48 MH - Apolipoproteins B/drug effects/immunology/*metabolism MH - Cells, Cultured MH - Chromosome Mapping MH - Epitopes MH - Fibrinolytic Agents/metabolism MH - Fibroblasts/metabolism MH - Humans MH - Immunoglobulin Fab Fragments/immunology MH - Peptide Fragments/immunology MH - Receptors, LDL/drug effects/immunology/*metabolism MH - Recombinant Fusion Proteins/immunology MH - beta-Galactosidase/immunology EDAT- 1992/08/01 00:00 MHDA- 1992/08/01 00:01 CRDT- 1992/08/01 00:00 PHST- 1992/08/01 00:00 [pubmed] PHST- 1992/08/01 00:01 [medline] PHST- 1992/08/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1992 Aug;33(8):1111-21. PMID- 1512509 OWN - NLM STAT- MEDLINE DCOM- 19920928 LR - 20131121 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 33 IP - 6 DP - 1992 Jun TI - Defective catabolism of oxidized LDL by J774 murine macrophages. PG - 819-29 AB - In J774 murine macrophages, chemically oxidized LDL (OxLDL) and biologically oxidized LDL (BioOxLDL) have similar metabolic fates, characterized by a relatively poor degradation when compared with acetylated LDL (AcLDL), and a modest ability to activate acyl-CoA:cholesterol acyltransferase (ACAT) (850 and 754 pmol [14C]oleate/mg cell protein in OxLDL- and BioOxLDL-incubated cells, versus 425 and 7070 pmol [14C]cholesteryl oleate/mg cell protein in control and AcLDL-incubated cells) with a massive increase of cellular free cholesterol. Therefore, OxLDL were used to investigate the cellular processing of oxidatively modified LDL. Binding and fluorescence microscopy studies demonstrated that OxLDL are effectively bound and internalized by macrophages and accumulate in organelles with density properties similar to those of endo/lysosomes. Although the overall metabolism of OxLDL is modestly affected by 100 microM chloroquine, owing to the poor cellular degradation of the substrate, the drug can further depress OxLDL degradation, indicating that this process takes place in an acidic compartment. Failure to detect products of extensive degradation of OxLDL in the medium is due to their relative resistance to enzymatic hydrolysis, as demonstrated also by in vitro experiments with partially purified lysosomal enzymes, rather than to the intracellular accumulation of degradation products (degraded intracellular protein is, at most, 8.5% of total). This sluggish degradation process is not due to a cytotoxic effect since OxLDL do not affect the intracellular processing of other ligands like AcLDL or IgG. The accumulation of OxLDL-derived products within macrophages may elicit cellular responses, the relevance of which in the atherosclerotic process remains to be addressed. FAU - Roma, P AU - Roma P AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Bernini, F AU - Bernini F FAU - Fogliatto, R AU - Fogliatto R FAU - Bertulli, S M AU - Bertulli SM FAU - Negri, S AU - Negri S FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Linolenic Acids) RN - 0 (Lipoproteins, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Cell Line MH - Cholesterol/metabolism MH - Linolenic Acids/metabolism MH - Lipoproteins, LDL/*metabolism MH - Lysosomes/metabolism MH - Macrophages/*metabolism MH - Mice MH - Oxidation-Reduction EDAT- 1992/06/01 00:00 MHDA- 1992/06/01 00:01 CRDT- 1992/06/01 00:00 PHST- 1992/06/01 00:00 [pubmed] PHST- 1992/06/01 00:01 [medline] PHST- 1992/06/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1992 Jun;33(6):819-29. PMID- 1505652 OWN - NLM STAT- MEDLINE DCOM- 19920924 LR - 20181113 IS - 0393-2990 (Print) IS - 0393-2990 (Linking) VI - 8 Suppl 1 DP - 1992 May TI - Characterization of a family with moderate hypercholesterolemia and binding defective low density lipoprotein. PG - 26-32 AB - Familial defective apolipoprotein B-100 (FDB) is a genetic disorder presenting with hypercholesterolemia and abnormal low density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B gene. In the present study thirteen members of a family with moderate hypercholesterolemia (250-350 mg/dl) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolemia (receptor deficiency). LDL from nine affected members displayed, in an "in vitro" cell binding assay, a reduced affinity (2.5 fold) for the receptor, and had normal electrophoretic mobility, size and chemical composition. Lp(a) levels in family members were comparable to those present in normolipidemics and lower than those observed in primary hypercholesterolemia. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolemic. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Corsini, A AU - Corsini A FAU - Mazzotti, M AU - Mazzotti M FAU - Granata, A AU - Granata A FAU - Uboldi, P AU - Uboldi P FAU - Maggi, F M AU - Maggi FM FAU - Romano, L AU - Romano L FAU - Romano, C AU - Romano C FAU - Fantappie, S AU - Fantappie S FAU - Fumagalli, R AU - Fumagalli R LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Eur J Epidemiol JT - European journal of epidemiology JID - 8508062 RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoproteins B) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Apolipoprotein B-100 MH - Apolipoproteins B/*genetics/metabolism MH - Binding Sites/physiology MH - Child MH - Female MH - Heterozygote MH - Humans MH - Hyperlipoproteinemia Type II/diagnosis/*genetics/metabolism MH - Lipoproteins, LDL/*genetics/metabolism MH - Male MH - Middle Aged MH - Receptors, LDL/*genetics/metabolism EDAT- 1992/05/01 00:00 MHDA- 1992/05/01 00:01 CRDT- 1992/05/01 00:00 PHST- 1992/05/01 00:00 [pubmed] PHST- 1992/05/01 00:01 [medline] PHST- 1992/05/01 00:00 [entrez] PST - ppublish SO - Eur J Epidemiol. 1992 May;8 Suppl 1:26-32. PMID- 1596308 OWN - NLM STAT- MEDLINE DCOM- 19920701 LR - 20061115 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 93 IP - 1-2 DP - 1992 Mar TI - Ability of the LDL receptor from several animal species to recognize the human apo B binding domain: studies with LDL from familial defective apo B-100. PG - 95-103 AB - To verify whether the LDL receptors from different animal species recognize the binding domain of human apo B-100 we studied the interaction of LDL from control and familial binding defective apo B-100 (FDB) with cultured cells. Human, monkey, bovine, guinea pig and rabbit LDL receptors distinguish between normal and binding defective LDL with a displacement ratio (defective/normal) of 3.3, 2.6, 3.4, 3.1 and 2.0, respectively. Guinea pig and rabbit receptors, however, showed affinities 2-3-fold lower than the human receptor. Hamster, rat and mouse cells failed to differentiate between normal and FDB LDL with a ratio of 1.2, 0.8, and 1.4; the apparent affinities were 4-8 times lower than that of the human receptor. The data from the latter species suggest that the LDL receptor recognizes an area of human apo B different from the human receptor binding domain. The ability of antibody Mb47 to inhibit the binding of human LDL to human, rabbit and guinea pig but not to mouse cells further stresses this concept. Moreover, in 17 alpha-ethinyl estradiol-treated rats the rate of disappearance from plasma of FDB and control 125I-labelled LDL was identical, thus confirming the in vitro observations. These data suggest that the binding domain of the LDL receptor is functionally conserved in man, monkey, cow, rabbit and guinea pig, but is quite distinct in rat, mouse and hamster. FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Mazzotti, M AU - Mazzotti M FAU - Villa, A AU - Villa A FAU - Maggi, F M AU - Maggi FM FAU - Bernini, F AU - Bernini F FAU - Romano, L AU - Romano L FAU - Romano, C AU - Romano C FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoproteins B) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - Apolipoprotein B-100 MH - Apolipoproteins B/*genetics/metabolism MH - Binding, Competitive MH - Cattle MH - Cells, Cultured MH - Cricetinae MH - Guinea Pigs MH - Haplorhini MH - Humans MH - Hyperlipoproteinemia Type II/genetics/*metabolism MH - Lipoproteins, LDL/*metabolism MH - Male MH - Mice MH - Rabbits MH - Rats MH - Rats, Inbred Strains MH - Receptors, LDL/*metabolism MH - Species Specificity EDAT- 1992/03/01 00:00 MHDA- 1992/03/01 00:01 CRDT- 1992/03/01 00:00 PHST- 1992/03/01 00:00 [pubmed] PHST- 1992/03/01 00:01 [medline] PHST- 1992/03/01 00:00 [entrez] AID - 0021-9150(92)90203-S [pii] PST - ppublish SO - Atherosclerosis. 1992 Mar;93(1-2):95-103. PMID- 1352976 OWN - NLM STAT- MEDLINE DCOM- 19920819 LR - 20181130 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 92 IP - 2-3 DP - 1992 Feb TI - High density lipoproteins: physiopathology and clinical relevance. PG - 261-4 AB - On September 13-14 1991 a Symposium on High Density Lipoproteins: Physiopathology and Clinical Relevance was held in Bellagio (Italy). This Symposium was aimed at discussing various aspects of HDL from epidemiology to the most recent advances in the understanding of HDL metabolism and factors (diets, drugs) affecting their levels. FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Bernini, F AU - Bernini F FAU - Vergani, C AU - Vergani C FAU - Catapano, A L AU - Catapano AL LA - eng PT - Congress PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins, HDL) SB - IM MH - Coronary Disease/epidemiology/etiology MH - Epidemiologic Factors MH - Humans MH - Hypolipoproteinemias/complications/epidemiology/metabolism MH - Lipoproteins, HDL/deficiency/*metabolism EDAT- 1992/02/01 00:00 MHDA- 1992/02/01 00:01 CRDT- 1992/02/01 00:00 PHST- 1992/02/01 00:00 [pubmed] PHST- 1992/02/01 00:01 [medline] PHST- 1992/02/01 00:00 [entrez] AID - 0021-9150(92)90286-P [pii] PST - ppublish SO - Atherosclerosis. 1992 Feb;92(2-3):261-4. PMID- 1598076 OWN - NLM STAT- MEDLINE DCOM- 19920708 LR - 20180703 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 50 IP - 24 DP - 1992 TI - Plasma lipoproteins and cholesterol metabolism in Yoshida rats: an animal model of spontaneous hyperlipemia. PG - 1913-24 AB - The purpose of this study was to characterize the lipoprotein profile and cholesterol metabolism in Yoshida rats, a strain of inbred genetically hyperlipemic animals. For comparison, Brown Norway rats were used as control animals. Plasma cholesterol and triglycerides were higher in Yoshida as compared to Brown Norway, the elevation of cholesterol being due to a rise in HDL fraction. Triglyceride distribution among lipoproteins showed an increase in VLDL fraction. Hyperlipemia was not related to diabetes, hypothyroidism or nephropathy. Plasma triglycerides production was increased in Yoshida rats, while lipoprotein and hepatic lipases were similar in the two groups. Hypercholesterolemia was associated with a defect of lipoprotein receptor activity and with elevated HMG-CoA reductase and cholesterol 7 alpha - hydroxylase; conversely ACAT activity was lower in Yoshida as compared to Brown Norway rats. Sterol fecal excretion was comparable in the two groups and hypercholesterolemia in Yoshida rats was not associated to an increase of cholesterol saturation of the bile. We suggest that lipoprotein overproduction is the main cause for hyperlipidemia in this strain of rats. FAU - Fantappie, S AU - Fantappie S AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Catapano, A L AU - Catapano AL FAU - Cancellieri, M AU - Cancellieri M FAU - Fasoli, L AU - Fasoli L FAU - De Fabiani, E AU - De Fabiani E FAU - Bertolini, M AU - Bertolini M FAU - Bosisio, E AU - Bosisio E LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Blood Glucose) RN - 0 (Lipoproteins) RN - 0 (Thyroid Hormones) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) SB - IM MH - Animals MH - Blood Glucose/metabolism MH - Body Weight/physiology MH - Cholesterol/blood/*metabolism MH - Disease Models, Animal MH - Hydroxymethylglutaryl CoA Reductases/metabolism MH - Hyperlipidemias/blood/enzymology/*metabolism MH - Hyperlipoproteinemia Type II/blood/enzymology/metabolism MH - Lipoproteins/*blood MH - Liver/anatomy & histology/enzymology/metabolism MH - Male MH - Organ Size/physiology MH - Rats MH - Rats, Inbred BN MH - Rats, Inbred Strains MH - Thyroid Hormones/blood MH - Triglycerides/blood/metabolism EDAT- 1992/01/01 00:00 MHDA- 1992/01/01 00:01 CRDT- 1992/01/01 00:00 PHST- 1992/01/01 00:00 [pubmed] PHST- 1992/01/01 00:01 [medline] PHST- 1992/01/01 00:00 [entrez] AID - 0024-3205(92)90552-Z [pii] PST - ppublish SO - Life Sci. 1992;50(24):1913-24. PMID- 1936106 OWN - NLM STAT- MEDLINE DCOM- 19911213 LR - 20061115 IS - 0014-2972 (Print) IS - 0014-2972 (Linking) VI - 21 IP - 4 DP - 1991 Aug TI - Familial defective apo B-100, characterization of an Italian family. PG - 389-97 AB - Familial defective apolipoprotein (apo) B-100 is a genetic disorder presenting with hypercholesterolaemia and abnormal low-density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B-100 gene. In the present study thirteen members of a family with moderate hypercholesterolaemia (250-350 mg dl-1) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolaemia (FH, receptor deficiency). We then studied the interaction between LDL and their receptors by an in vitro cell binding assay. LDL from nine affected members displayed a reduced affinity (2.5-fold) for the receptor, and were less effective than LDL from control and unaffected members in suppressing LDL receptor expression and in stimulating cholesterol esterification. LDL from the affected members had normal electrophoretic mobility, size and chemical composition. Partial delipidation did not modify the LDL binding defect. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolaemics. Analysis of DNA from family members showed a point mutation leading to an Arg to Gln substitution at amino acid 3500 of the mature protein that segregated with hypercholesterolaemia and LDL defective binding. We conclude that this family is affected by familial defective apolipoprotein B-100 (FDB). FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - McCarthy, B J AU - McCarthy BJ FAU - Granata, A AU - Granata A FAU - Soria, L F AU - Soria LF FAU - Fantappie, S AU - Fantappie S FAU - Bernini AU - Bernini FAU - Romano, C AU - Romano C FAU - Romano, L AU - Romano L FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 0 (Apolipoprotein B-100) RN - 0 (Apolipoproteins B) RN - 0 (DNA Probes) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) RN - 9007-49-2 (DNA) SB - IM MH - Adolescent MH - Apolipoprotein B-100 MH - Apolipoproteins B/*genetics MH - Base Sequence MH - DNA/genetics MH - DNA Probes MH - Humans MH - Hyperlipoproteinemia Type II/blood/*genetics MH - Lipoproteins, LDL/blood/genetics MH - Male MH - Molecular Sequence Data MH - Mutation MH - Pedigree MH - Polymerase Chain Reaction MH - Receptors, LDL/metabolism EDAT- 1991/08/01 00:00 MHDA- 1991/08/01 00:01 CRDT- 1991/08/01 00:00 PHST- 1991/08/01 00:00 [pubmed] PHST- 1991/08/01 00:01 [medline] PHST- 1991/08/01 00:00 [entrez] PST - ppublish SO - Eur J Clin Invest. 1991 Aug;21(4):389-97. PMID- 1889447 OWN - NLM STAT- MEDLINE DCOM- 19911017 LR - 20131121 IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 12 IP - 7 DP - 1991 Jul TI - Aortic and coronary atheromatosis in a woman with severe hypercholesterolaemia without LDL receptor alterations. PG - 818-24 AB - Familial hypercholesterolaemia (FH) is a monogenic disorder, with a strong family history, characterized by a deficiency in functional receptors for low density lipoproteins (LDL). The case of a patient with all the clinical traits of FH, including elevated cholesterol, xanthomas and early coronary and peripheral arterial lesions, but with a normal LDL receptor function, is described. In the patient the molecular weight and immunological properties of apolipoprotein (apo) B were normal; furthermore, autoantibodies to either LDL or to their receptor were also absent. The increased apo B/cholesterol ratio in LDL was compatible with the diagnosis of hyperapobetalipoproteinaemia. With the help of a turnover study using 131I homologous and 125I autologous LDL, it could be established that the patient had an almost three-fold increase in LDL-apo B biosynthesis, with, however, a fractional catabolic rate within normal limits. These findings pointed to the possibility of a genomic alteration in the region responsible for the control of apo B biosynthesis. However, extensive studies both at the cDNA level and in the 5' region of the apo B gene, failed to detect any significant alteration vs published nucleotide sequences. Although the exact mechanism for this unusual clinical presentation of an FH-like syndrome could not be uncovered, this case provides an extreme example of hypercholesterolaemia, with early and severe arterial disease, solely explained by an increased LDL biosynthesis. FAU - Sirtori, C R AU - Sirtori CR AD - Center E. Grossi Paoletti, University of Milano, Italy. FAU - Catapano, A L AU - Catapano AL FAU - Franceschini, G AU - Franceschini G FAU - Corsini, A AU - Corsini A FAU - Noseda, G AU - Noseda G FAU - Fragiacomo, C AU - Fragiacomo C FAU - Panzeri, E AU - Panzeri E FAU - Vaccarino, V AU - Vaccarino V FAU - Guenzi, S AU - Guenzi S FAU - Casari, G AU - Casari G AU - et al. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Apolipoproteins B) RN - 0 (Cholesterol, LDL) RN - 0 (Receptors, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Aortic Diseases/*etiology MH - Apolipoproteins B/blood/genetics MH - Arteriosclerosis/*etiology MH - Base Sequence MH - Cholesterol/blood MH - Cholesterol, LDL/blood MH - Coronary Artery Disease/*etiology MH - Female MH - Humans MH - Hyperlipoproteinemia Type II/blood/*complications/metabolism MH - Middle Aged MH - Molecular Sequence Data MH - Promoter Regions, Genetic/genetics MH - Receptors, LDL/metabolism EDAT- 1991/07/01 00:00 MHDA- 1991/07/01 00:01 CRDT- 1991/07/01 00:00 PHST- 1991/07/01 00:00 [pubmed] PHST- 1991/07/01 00:01 [medline] PHST- 1991/07/01 00:00 [entrez] PST - ppublish SO - Eur Heart J. 1991 Jul;12(7):818-24. PMID- 1851638 OWN - NLM STAT- MEDLINE DCOM- 19910627 LR - 20161126 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1083 IP - 1 DP - 1991 Apr 24 TI - Cholesterol stimulation of HDL binding to human endothelial cells EAhy 926 and skin fibroblasts: evidence for a mechanism independent of cellular metabolism. PG - 94-100 AB - The properties of the HDL binding site on the permanent human cell line EAhy 926 were studied. This cell line presents with highly differentiated functions of vascular endothelium. EAhy 926 cells possess HDL3 saturable binding sites with a Kd of about 20 micrograms/ml, which were up-regulated by cholesterol and were pronase- and EDTA-insensitive. Furthermore, HDL3 promoted cholesterol efflux from EAhy 926 cells in a dose-dependent manner. Thus, the HDL-binding site in EAhy 926 cells is similar to that present in fibroblasts, smooth muscle cells and endothelial cells. Up-regulation of HDL binding by cholesterol did not require de novo synthesis of HDL 'receptor' protein, as shown by the lack of effect of cycloheximide and alpha-amanitin and also occurred in fixed, non-living cells. Similar results were obtained using human skin fibroblasts. From these data we conclude that: (a) EAhy 926 cells are a good model for studying the HDL interaction with endothelial cells; (b) a mechanism independent of cellular metabolism is involved in the cholesterol-mediated up-regulation of HDL binding sites in EAhy 926 cells and human skin fibroblasts. FAU - Bernini, F AU - Bernini F AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Bellosta, S AU - Bellosta S FAU - Corsini, A AU - Corsini A FAU - Maggi, F M AU - Maggi FM FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Carrier Proteins) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Liposomes) RN - 0 (RNA-Binding Proteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, LDL) RN - 0 (Receptors, Lipoprotein) RN - 0 (high density lipoprotein receptors) RN - 147605-06-9 (high density lipoprotein binding protein) RN - 97C5T2UQ7J (Cholesterol) RN - 98600C0908 (Cycloheximide) SB - IM MH - Binding, Competitive MH - *Carrier Proteins MH - Cell Line MH - Cholesterol/metabolism/pharmacology MH - Cycloheximide/pharmacology MH - Endothelium, Vascular/*metabolism MH - Fibroblasts/drug effects/metabolism MH - Humans MH - Kinetics MH - Lipoproteins, HDL/*metabolism MH - Lipoproteins, LDL/metabolism MH - Liposomes MH - *RNA-Binding Proteins MH - Receptors, Cell Surface/*metabolism MH - Receptors, LDL/metabolism MH - *Receptors, Lipoprotein MH - Skin/*metabolism EDAT- 1991/04/24 00:00 MHDA- 1991/04/24 00:01 CRDT- 1991/04/24 00:00 PHST- 1991/04/24 00:00 [pubmed] PHST- 1991/04/24 00:01 [medline] PHST- 1991/04/24 00:00 [entrez] AID - 0005-2760(91)90129-6 [pii] PST - ppublish SO - Biochim Biophys Acta. 1991 Apr 24;1083(1):94-100. PMID- 1671145 OWN - NLM STAT- MEDLINE DCOM- 19910222 LR - 20170920 IS - 0140-6736 (Print) IS - 0140-6736 (Linking) VI - 337 IP - 8736 DP - 1991 Feb 2 TI - Poor response to simvastatin in familial defective apo-B-100. PG - 305 FAU - Corsini, A AU - Corsini A FAU - Mazzotti, M AU - Mazzotti M FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL FAU - Romano, L AU - Romano L FAU - Romano, C AU - Romano C LA - eng PT - Comparative Study PT - Letter PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Anticholesteremic Agents) RN - 0 (Apolipoproteins B) RN - 0 (Receptors, LDL) RN - 9LHU78OQFD (Lovastatin) RN - AGG2FN16EV (Simvastatin) SB - AIM SB - IM MH - Anticholesteremic Agents/*metabolism MH - Apolipoproteins B/*genetics MH - Humans MH - Hyperlipoproteinemia Type II/*metabolism MH - Lovastatin/*analogs & derivatives/metabolism MH - Receptors, LDL/drug effects/*metabolism MH - Simvastatin EDAT- 1991/02/02 00:00 MHDA- 1991/02/02 00:01 CRDT- 1991/02/02 00:00 PHST- 1991/02/02 00:00 [pubmed] PHST- 1991/02/02 00:01 [medline] PHST- 1991/02/02 00:00 [entrez] AID - 0140-6736(91)90920-K [pii] PST - ppublish SO - Lancet. 1991 Feb 2;337(8736):305. PMID- 2062789 OWN - NLM STAT- MEDLINE DCOM- 19910806 LR - 20150831 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 23 IP - 2 DP - 1991 Feb TI - Reduction of LDL production rate in ileal bypassed rabbits treated with lovastatin. PG - 129-37 AB - The effect of lovastatin on the low density lipoprotein metabolism in bypassed rabbits was investigated. Partial ileal bypass effectively reduced total and low density lipoprotein (LDL) cholesterol by 44 and 48% respectively. The LDL drop was due to an increased fractional catabolic rate (FCR) of apolipoprotein B (apo B) from 0.74 to 1.27 pools per day with no effect on the apo B absolute catabolic rate and an increased expression of liver LDL receptors (+71%). Association of lovastatin with PIB resulted in a further decrease of total and LDL cholesterol (56 and 75% respectively) as compared to bypassed animals, without effects on the LDL FCR (1.27 +/- 0.11 versus 1.42 +/- 0.13 pools/day) or the expression of LDL receptors by the liver. The reduction of LDL was due to a decrease of the apolipoprotein B absolute synthetic rate (8.5 +/- 1.7 versus 13.6 +/- 1.7 mg/day). From these data we conclude that in bypassed rabbits lovastatin lowers total and LDL cholesterol mainly by reducing apolipoprotein B production rate. FAU - Lombardi, P AU - Lombardi P AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Maggi, F M AU - Maggi FM FAU - Maione, G AU - Maione G FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Apolipoproteins B) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) RN - 9LHU78OQFD (Lovastatin) SB - IM MH - Animals MH - Apolipoproteins B/metabolism MH - *Jejunoileal Bypass MH - Lipoproteins, LDL/*metabolism MH - Liver/metabolism MH - Lovastatin/*pharmacology MH - Male MH - Rabbits MH - Receptors, LDL/*metabolism EDAT- 1991/02/01 00:00 MHDA- 1991/02/01 00:01 CRDT- 1991/02/01 00:00 PHST- 1991/02/01 00:00 [pubmed] PHST- 1991/02/01 00:01 [medline] PHST- 1991/02/01 00:00 [entrez] AID - S1043-6618(05)80114-8 [pii] PST - ppublish SO - Pharmacol Res. 1991 Feb;23(2):129-37. PMID- 2393386 OWN - NLM STAT- MEDLINE DCOM- 19901004 LR - 20141120 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 171 IP - 1 DP - 1990 Aug 31 TI - Oxidized LDL increase free cholesterol and fail to stimulate cholesterol esterification in murine macrophages. PG - 123-31 AB - Oxidatively modified low density lipoproteins (Ox-LDL) may be involved in determining the formation of foam cells by inducing cellular cholesteryl ester accumulation. We studied the effect of copper oxidized LDL (Ox-LDL) on cholesterol accumulation and esterification in murine macrophages. Ox-LDL (44 micrograms/ml of lipoprotein cholesterol) increased the total cholesterol content of the cells from 29 to 69 micrograms/mg cell protein. Free cholesterol accounted for 85% of this increase. Acetyl LDL (Ac-LDL) (38 micrograms/ml of lipoprotein cholesterol), raised total cellular cholesterol content to a similar extent (76 micrograms/mg cell protein), however only 25% of the accumulated cholesterol was unesterified. When ACAT activity was determined after incubation of J774 cell with Ox- or Ac-LDL, Ox-LDL were 12 times less effective than Ac-LDL in stimulating cholesteryl ester formation. This was not due to an inhibition of ACAT by Ox-LDL since these lipoproteins failed to inhibit pre activated enzyme in cholesteryl ester-loaded macrophages. The uptake of 125I-Ox-LDL: was 175% that of 125I-Ac-LDL, while degradation was only 20%. All together these data suggest an altered intracellular processing of Ox-LDL, which may be responsible for free cholesterol accumulation. FAU - Roma, P AU - Roma P AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Catapano, A L AU - Catapano AL FAU - Bertulli, S M AU - Bertulli SM FAU - Varesi, L AU - Varesi L FAU - Fumagalli, R AU - Fumagalli R FAU - Bernini, F AU - Bernini F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Apolipoproteins B) RN - 0 (Cholesterol Esters) RN - 0 (Cholesterol, LDL) RN - 0 (Lipoproteins, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Acetylation MH - Animals MH - Apolipoproteins B/metabolism MH - Biological Transport MH - Cell Line MH - Cholesterol/*metabolism MH - Cholesterol Esters/metabolism MH - Cholesterol, LDL/metabolism MH - In Vitro Techniques MH - Lipoproteins, LDL/*metabolism MH - Macrophages/*metabolism MH - Mice MH - Oxidation-Reduction MH - Peritoneal Cavity/cytology EDAT- 1990/08/31 00:00 MHDA- 1990/08/31 00:01 CRDT- 1990/08/31 00:00 PHST- 1990/08/31 00:00 [pubmed] PHST- 1990/08/31 00:01 [medline] PHST- 1990/08/31 00:00 [entrez] AID - 0006-291X(90)91365-Y [pii] PST - ppublish SO - Biochem Biophys Res Commun. 1990 Aug 31;171(1):123-31. PMID- 1692868 OWN - NLM STAT- MEDLINE DCOM- 19900626 LR - 20061115 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 31 IP - 3 DP - 1990 Mar TI - Immunochemical characterization of six monoclonal antibodies to human apolipoprotein A-I: epitope mapping and expression. PG - 375-84 AB - We have produced and characterized six murine monoclonal antibodies to human apolipoprotein A-I named A-I-9, A-I-12, A-I-15, A-I-16, A-I-19, and A-I-57. All monoclonal antibodies were specific for apolipoprotein A-I and bound between 55% and 100% of 125I-labeled high density lipoproteins (HDL) in a fluid phase radioimmunoassay. All antibodies possessed a higher affinity to apoA-I in HDL than to free, delipidated apoA-I. Two of them, particularly A-I-12 and A-I-15, which were directed to the same or very close epitopes on the molecule, recognized very poorly the delipidated protein. Binding of apoA-I to phospholipid restored the immunoreactivity of the monoclonal antibodies to the protein suggesting that lipids play an important role in determining the immunochemical structure of apoA-I. Using CNBr fragments and synthetic peptides, the epitopes for the antibodies were mapped as follows: A-I-19, CNBr fragment 1; A-I-12 and 15, CNBr fragment 2; A-I-9 and A-I-16, CNBr fragment 3; A-I-57, CNBr fragment 4. Antibody A-I-57 failed to recognized a mutant form of apoA-I, A-IMilano (Arg173----Cys) by immunoblotting and by competitive radioimmunoassay demonstrating that substitution of a single amino acid in human apoA-I may cause the loss of an antigenic determinant. FAU - Marcovina, S AU - Marcovina S AD - Laboratory of Immunochemistry and Lipoproteins, Scientific Institute S. Raffaele, Milan, Italy. FAU - Fantappie, S AU - Fantappie S FAU - Zoppo, A AU - Zoppo A FAU - Franceschini, G AU - Franceschini G FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins A) RN - 0 (Epitopes) RN - 0 (Lipoproteins, HDL) RN - 0 (Peptide Fragments) SB - IM MH - Animals MH - Antibodies, Monoclonal/*biosynthesis/immunology MH - Antibody Specificity MH - Apolipoprotein A-I MH - Apolipoproteins A/genetics/*immunology MH - Binding, Competitive MH - Electrophoresis, Polyacrylamide Gel MH - Epitopes/*immunology MH - Humans MH - Immunoblotting MH - Lipoproteins, HDL/immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mutation MH - Peptide Fragments/chemical synthesis/immunology MH - Peptide Mapping MH - Radioimmunoassay EDAT- 1990/03/01 00:00 MHDA- 1990/03/01 00:01 CRDT- 1990/03/01 00:00 PHST- 1990/03/01 00:00 [pubmed] PHST- 1990/03/01 00:01 [medline] PHST- 1990/03/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1990 Mar;31(3):375-84. PMID- 2554710 OWN - NLM STAT- MEDLINE DCOM- 19891212 LR - 20170908 IS - 0002-9149 (Print) IS - 0002-9149 (Linking) VI - 64 IP - 17 DP - 1989 Nov 7 TI - Effects of calcium antagonists on lipids and atherosclerosis. PG - 129I-133I; discussion 133I-134I AB - The arterial accumulation of cholesterol and calcium is a hallmark of atherosclerosis. Calcium antagonists (CAs) lessen the severity of experimentally induced atherosclerosis in cholesterol-fed animals. The reduction of aortic cholesterol is one of the most striking findings. This effect is achieved without a reduction of plasma lipid or blood pressure, and is probably related to an interference of CAs with lipid metabolism in the arterial wall. To what extent these properties of CAs are due to their ability to block calcium channels still remains to be addressed. This report briefly discusses the available in vivo and in vitro evidence for the antiatherosclerotic properties of CAs, and outlines the possible mechanisms by which these compounds affect cellular lipid metabolism. FAU - Bernini, F AU - Bernini F AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Catapano, A L AU - Catapano AL FAU - Corsini, A AU - Corsini A FAU - Fumagalli, R AU - Fumagalli R FAU - Paoletti, R AU - Paoletti R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Calcium Channel Blockers) RN - 0 (Cholesterol Esters) RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Lipoprotein) SB - AIM SB - IM MH - Animals MH - Arteriosclerosis/*prevention & control MH - Biomechanical Phenomena MH - Calcium Channel Blockers/pharmacokinetics/*pharmacology MH - Cholesterol Esters/metabolism MH - Esterification MH - Hydrolysis MH - Lipids/*blood MH - Lipoproteins/antagonists & inhibitors/metabolism MH - Lipoproteins, LDL/metabolism MH - Lysosomes/metabolism MH - Receptors, Cell Surface/metabolism MH - Receptors, Lipoprotein RF - 44 EDAT- 1989/11/07 00:00 MHDA- 1989/11/07 00:01 CRDT- 1989/11/07 00:00 PHST- 1989/11/07 00:00 [pubmed] PHST- 1989/11/07 00:01 [medline] PHST- 1989/11/07 00:00 [entrez] AID - 0002-9149(89)90970-3 [pii] PST - ppublish SO - Am J Cardiol. 1989 Nov 7;64(17):129I-133I; discussion 133I-134I. PMID- 2633155 OWN - NLM STAT- MEDLINE DCOM- 19900511 LR - 20150831 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 21 Suppl 1 DP - 1989 Nov-Dec TI - Effect of bezafibrate on plasma lipid in a strain of genetically hypercholesterolemic RICO rats. PG - 109-10 FAU - Fantappie, S AU - Fantappie S AD - Institute of Pharmacological Sciences, University of Milano, Italy. FAU - Maggi, F M AU - Maggi FM FAU - Cancellieri, M AU - Cancellieri M FAU - Bosisio, E AU - Bosisio E FAU - Malavasi, B AU - Malavasi B FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anticholesteremic Agents) RN - 0 (Lipids) RN - 0 (Lipoproteins, VLDL) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) RN - Y9449Q51XH (Bezafibrate) SB - IM MH - Animals MH - *Anticholesteremic Agents MH - Bezafibrate/*pharmacology MH - Hydroxymethylglutaryl CoA Reductases/metabolism MH - Hypercholesterolemia/blood/*genetics MH - Lipids/*blood MH - Lipoproteins, VLDL/blood MH - Rats EDAT- 1989/11/01 00:00 MHDA- 1989/11/01 00:01 CRDT- 1989/11/01 00:00 PHST- 1989/11/01 00:00 [pubmed] PHST- 1989/11/01 00:01 [medline] PHST- 1989/11/01 00:00 [entrez] PST - ppublish SO - Pharmacol Res. 1989 Nov-Dec;21 Suppl 1:109-10. PMID- 2475112 OWN - NLM STAT- MEDLINE DCOM- 19890921 LR - 20141120 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 162 IP - 3 DP - 1989 Aug 15 TI - Monoclonal antibody 5A binds apolipoprotein B-48 and inhibits the low density lipoprotein-receptor interaction. PG - 908-15 AB - In a panel of 10 monoclonal antibodies raised against human LDL we detected three antibodies (named 5A, 6B, and 6E) which recognize both apolipoprotein B-100 and B-48. Antibody 5A inhibited, in a dose dependent manner, the interaction of 125I-LDL with their receptor on human skin fibroblasts. Using thrombolytic fragments, the epitope of antibody 5A was mapped to the carboxy terminal region of apo B-48. MAB 5A was equipotent with MAB Mb 47, an inhibitory antibody whose epitope lies near a putative receptor binding domain of apo B in thrombolytic fragment T2. These findings suggest that areas other than the carboxy terminal portion of apo B-100 may participate in the LDL-receptor interaction, either directly or by determining the exposition of high affinity sites of apo B-100. FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, University of Milan, Italy. FAU - Fantappie, S AU - Fantappie S FAU - Marcovina, S AU - Marcovina S FAU - Granata, A AU - Granata A FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein B-48) RN - 0 (Apolipoproteins B) RN - 0 (Epitopes) RN - 0 (Lipoproteins, LDL) RN - 0 (Peptide Fragments) RN - 0 (Receptors, LDL) SB - IM MH - Antibodies, Monoclonal/*immunology MH - Antibody Specificity MH - Antigen-Antibody Reactions MH - Apolipoprotein B-48 MH - Apolipoproteins B/*immunology/metabolism MH - Binding Sites MH - Endocytosis MH - Epitopes MH - Humans MH - In Vitro Techniques MH - Lipoproteins, LDL/immunology/*metabolism MH - Peptide Fragments/immunology MH - Receptors, LDL/*metabolism EDAT- 1989/08/15 00:00 MHDA- 1989/08/15 00:01 CRDT- 1989/08/15 00:00 PHST- 1989/08/15 00:00 [pubmed] PHST- 1989/08/15 00:01 [medline] PHST- 1989/08/15 00:00 [entrez] AID - 0006-291X(89)90758-4 [pii] PST - ppublish SO - Biochem Biophys Res Commun. 1989 Aug 15;162(3):908-15. PMID- 2500972 OWN - NLM STAT- MEDLINE DCOM- 19890817 LR - 20170915 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1003 IP - 3 DP - 1989 Jun 28 TI - Assimilation of LDL by experimental tumours in mice. PG - 301-6 AB - We have studied the uptake of 125I-labelled low-density lipoprotein (LDL) by seven experimental murine tumours in vivo. Four tumours (Lewis Lung carcinoma, B-16, MS-2 and Colon 26) showed a higher relative uptake of lipoprotein as compared to the liver, two (L-1210 and P-388) had a very low lipoprotein uptake, while lipoprotein uptake by tumour M5 was similar to that of the liver. The data was confirmed by tracing tissue uptake of lipoproteins using [14C]sucrose-labeled LDL. These in vivo findings correlated well with the in vitro specific binding of 125I-beta-VLDL to membranes prepared from tumours, thus suggesting that the expression of the LDL receptor in the tumours is related to the in vivo uptake of lipoprotein. Further analysis of the LDL receptor by ligand blotting showed that the tumor receptor has several of the liver LDL receptor characteristics (including apparent Mr, sensitivity to proteinases, and Ca2+ requirement of lipoprotein binding). In summary, our data show that experimental murine tumours express the LDL receptor and suggest that the high relative in vivo uptake of LDL is determined by the elevated LDL-receptor expression in the tumours. FAU - Lombardi, P AU - Lombardi P AD - Institute of Pharmacological Sciences, School of Pharmacy, Milan, Italy. FAU - Norata, G AU - Norata G FAU - Maggi, F M AU - Maggi FM FAU - Canti, G AU - Canti G FAU - Franco, P AU - Franco P FAU - Nicolin, A AU - Nicolin A FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Receptors, LDL) RN - 60-24-2 (Mercaptoethanol) RN - 9G34HU7RV0 (Edetic Acid) RN - EC 3.4.24.- (Pronase) SB - IM MH - Animals MH - Biological Transport MH - Cell Membrane/metabolism MH - Edetic Acid/pharmacology MH - Kinetics MH - Lipoproteins, LDL/*metabolism MH - Lipoproteins, VLDL/metabolism MH - Liver/metabolism MH - Mercaptoethanol/pharmacology MH - Mice MH - Neoplasms, Experimental/*metabolism MH - Pronase/pharmacology MH - Receptors, LDL/*metabolism EDAT- 1989/06/28 00:00 MHDA- 1989/06/28 00:01 CRDT- 1989/06/28 00:00 PHST- 1989/06/28 00:00 [pubmed] PHST- 1989/06/28 00:01 [medline] PHST- 1989/06/28 00:00 [entrez] AID - 0005-2760(89)90236-1 [pii] PST - ppublish SO - Biochim Biophys Acta. 1989 Jun 28;1003(3):301-6. PMID- 2730713 OWN - NLM STAT- MEDLINE DCOM- 19890629 LR - 20161123 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 76 IP - 2-3 DP - 1989 Apr TI - Plasma lipoproteins and cholesterol metabolism in spontaneously hyperlipemic rats. PG - 163-71 AB - The aim of this study was to characterize the plasma lipoprotein pattern and some aspects of cholesterol metabolism in a line of hyperlipemic male rats. Plasma cholesterol and triglycerides were increased about 3-fold as compared to control animals (238 vs. 75 and 185 vs. 59 mg/dl respectively). The plasma lipoprotein distribution and the chemical composition of the isolated lipoproteins was unaffected. Plasma triglyceride production rate was increased (40%, P less than 0.01) and post-heparin lipoprotein lipase activity in plasma decreased (-28%, P less than 0.01) in the hyperlipemic rat. The activity of 3 enzymes involved in cholesterol metabolism (HMG-CoA reductase, cholesterol 7 alpha-hydroxylase, and acyl-CoA cholesterol-acyltransferase) did not differ from control values. 3H2O incorporation into digitonin-precipitable sterols, however, was significantly higher than in controls. This finding was due, in part, to an increased liver weight in the hyperlipemic animals. Furthermore kinetic data using 125I-LDL showed that the fractional catabolic rate of lipoprotein was within the normal range, while the synthetic rate of LDL protein was increased (0.67 vs. 0.3 mg/kg/h, P less than 0.01) in the hyperlipemic rat. These observations suggest that multiple metabolic defects underline the hyperlipemia observed in this animal model. FAU - Fantappie, S AU - Fantappie S AD - Institute of Pharmacological Sciences, School of Pharmacy, University of Milan, Italy. FAU - Crestani, M AU - Crestani M FAU - Bosisio, E AU - Bosisio E FAU - Galli, G AU - Galli G FAU - Maggi, F M AU - Maggi FM FAU - Corsini, A AU - Corsini A FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins, LDL) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) RN - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase) RN - EC 2.3.1.26 (Sterol O-Acyltransferase) SB - IM MH - Animals MH - Cholesterol/*metabolism MH - Cholesterol 7-alpha-Hydroxylase/metabolism MH - Hydroxymethylglutaryl CoA Reductases/metabolism MH - Hyperlipidemias/enzymology/*metabolism MH - Lipoproteins, LDL/blood/*metabolism MH - Models, Biological MH - Rats MH - Rats, Inbred Strains MH - Sterol O-Acyltransferase/metabolism EDAT- 1989/04/01 00:00 MHDA- 1989/04/01 00:01 CRDT- 1989/04/01 00:00 PHST- 1989/04/01 00:00 [pubmed] PHST- 1989/04/01 00:01 [medline] PHST- 1989/04/01 00:00 [entrez] AID - 0021-9150(89)90100-7 [pii] PST - ppublish SO - Atherosclerosis. 1989 Apr;76(2-3):163-71. PMID- 2564152 OWN - NLM STAT- MEDLINE DCOM- 19890419 LR - 20150616 IS - 0140-6736 (Print) IS - 0140-6736 (Linking) VI - 1 IP - 8638 DP - 1989 Mar 18 TI - Binding-defective low-density lipoprotein in family with hypercholesterolaemia. PG - 623 FAU - Corsini, A AU - Corsini A FAU - Fantappie, S AU - Fantappie S FAU - Granata, A AU - Granata A FAU - Bernini, F AU - Bernini F FAU - Catapano, A L AU - Catapano AL FAU - Fumagalli, R AU - Fumagalli R FAU - Romano, L AU - Romano L FAU - Romano, C AU - Romano C LA - eng PT - Letter PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) SB - AIM SB - IM MH - Adult MH - Child MH - Child, Preschool MH - Female MH - Humans MH - Hyperlipoproteinemia Type II/*metabolism MH - Lipoproteins, LDL/genetics/*metabolism MH - Male MH - Middle Aged MH - Receptors, LDL/metabolism EDAT- 1989/03/18 00:00 MHDA- 1989/03/18 00:01 CRDT- 1989/03/18 00:00 PHST- 1989/03/18 00:00 [pubmed] PHST- 1989/03/18 00:01 [medline] PHST- 1989/03/18 00:00 [entrez] AID - S0140-6736(89)91659-0 [pii] PST - ppublish SO - Lancet. 1989 Mar 18;1(8638):623. PMID- 2726662 OWN - NLM STAT- MEDLINE DCOM- 19890630 LR - 20180530 IS - 1043-6618 (Print) IS - 1043-6618 (Linking) VI - 21 IP - 1 DP - 1989 Jan-Feb TI - Effects of coffee on plasma lipids, lipoproteins and apolipoproteins. PG - 27-38 AB - The acute effects of coffee, cigarette smoking and alcohol on serum lipids, lipoproteins and thromboxane B2 production by platelets were studied in nine healthy volunteers who were non-drinkers of coffee and alcohol and non-smokers. They received, in a single administration, coffee (containing 200 mg of caffeine), alcohol (0.50 ml/kg body wt), or smoked two cigarettes. No differences were observed between baseline and 15, 60 and 80 min values for plasma cholesterol, triglycerides, HDL cholesterol, plasma apolipoproteins A-I and B and thromboxane B2 production. Chronic coffee consumption also did not affect either plasma lipoprotein profile or the interaction of low density lipoproteins with cellular receptors in a group of healthy individuals. These results suggest that coffee itself does not affect acutely the plasma lipoprotein profile in healthy man. This was also true in heavy coffee drinkers. FAU - Paoletti, R AU - Paoletti R AD - Institute of Pharmacological Sciences, Milano, Italy. FAU - Corsini, A AU - Corsini A FAU - Tremoli, E AU - Tremoli E FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Apolipoproteins) RN - 0 (Coffee) RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 54397-85-2 (Thromboxane B2) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adult MH - Apolipoproteins/*blood MH - Cholesterol/blood MH - *Coffee MH - Humans MH - Lipids/*blood MH - Lipoproteins/*blood MH - Male MH - Middle Aged MH - Thromboxane B2/biosynthesis EDAT- 1989/01/01 00:00 MHDA- 1989/01/01 00:01 CRDT- 1989/01/01 00:00 PHST- 1989/01/01 00:00 [pubmed] PHST- 1989/01/01 00:01 [medline] PHST- 1989/01/01 00:00 [entrez] AID - 1043-6618(89)90118-7 [pii] PST - ppublish SO - Pharmacol Res. 1989 Jan-Feb;21(1):27-38. PMID- 2675133 OWN - NLM STAT- MEDLINE DCOM- 19891025 LR - 20061115 IS - 0163-7258 (Print) IS - 0163-7258 (Linking) VI - 43 IP - 2 DP - 1989 TI - The low density lipoprotein receptor: structure, function and pharmacological modulation. PG - 187-219 FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Pharmacol Ther JT - Pharmacology & therapeutics JID - 7905840 RN - 0 (Receptors, LDL) SB - IM MH - Animals MH - Humans MH - Receptors, LDL/analysis/drug effects/*metabolism RF - 126 EDAT- 1989/01/01 00:00 MHDA- 1989/01/01 00:01 CRDT- 1989/01/01 00:00 PHST- 1989/01/01 00:00 [pubmed] PHST- 1989/01/01 00:01 [medline] PHST- 1989/01/01 00:00 [entrez] AID - 0163-7258(89)90118-6 [pii] PST - ppublish SO - Pharmacol Ther. 1989;43(2):187-219. PMID- 3214471 OWN - NLM STAT- MEDLINE DCOM- 19890221 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 74 IP - 1-2 DP - 1988 Nov TI - Progesterone modulates the expression of HDL binding sites in human skin fibroblasts. PG - 107-13 AB - The aim of this work was to study the effects of progesterone on the expression of high density lipoprotein binding sites by cultured human skin fibroblasts. At concentrations ranging between 10(-6)- and 10(-4) M the hormone showed a dose-dependent induction of the HDL binding sites. The effect was maximal at 48 h. The increased HDL binding was only due to an up-regulation of binding sites, without changes of the apparent Kd. This effect was not related to changes of cellular cholesterol content, and was not affected by inhibition of protein synthesis. These data suggest that the expression of binding sites for HDL can be modulated via a mechanism that does not depend upon cellular cholesterol content. FAU - Corsini, A AU - Corsini A AD - Institute of Pharmacological Sciences, Milano, Italy. FAU - Granata, A AU - Granata A FAU - Bernini, F AU - Bernini F FAU - Maggi, F M AU - Maggi FM FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 4G7DS2Q64Y (Progesterone) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Binding Sites/drug effects MH - Cells, Cultured MH - Cholesterol/metabolism MH - Dose-Response Relationship, Drug MH - Fibroblasts/*metabolism MH - Humans MH - Lipoproteins, HDL/*metabolism MH - Lipoproteins, HDL3 MH - Progesterone/administration & dosage/*pharmacology EDAT- 1988/11/01 00:00 MHDA- 1988/11/01 00:01 CRDT- 1988/11/01 00:00 PHST- 1988/11/01 00:00 [pubmed] PHST- 1988/11/01 00:01 [medline] PHST- 1988/11/01 00:00 [entrez] AID - 0021-9150(88)90197-9 [pii] PST - ppublish SO - Atherosclerosis. 1988 Nov;74(1-2):107-13. PMID- 3150125 OWN - NLM STAT- MEDLINE DCOM- 19890612 LR - 20161123 IS - 0390-5748 (Print) IS - 0390-5748 (Linking) VI - 18 IP - 4 DP - 1988 Oct-Dec TI - Evaluation of apolipoproteins A-I and B as markers of angiographically assessed coronary artery disease. PG - 319-28 AB - The aim of this study was to evaluate the ability of plasma levels of apo A-I and apo B to discriminate between male patients with and without angiographically determined coronary artery disease (CAD) in comparison to the levels of cholesterol, HDL-cholesterol and triglycerides. The plasma apo A-I and B levels were measured by a radial immunodiffusion assay that made use of well characterized monoclonal antibodies. Univariate statistical analysis showed that the mean values for HDL-cholesterol and apo A-I were significantly lower in patients with single-, double- and triple-vessel disease than in the control subjects. The mean values for plasma cholesterol and apo B were significantly higher in the group with double- and triple-, but not single-vessel disease, than in the group without CAD. No statistically significant difference among groups was found for plasma triglyceride values. Since the considered variables failed to assess the severity of the disease, as determined by the number of vessels involved, the 3 groups of patients with CAD were combined into one group. A multiple logistic analysis, performed in order to assess the independent role of the variables and to estimate the corresponding odds ratio, indicated an independent association of HDL-cholesterol, apo A-I and apo B with CAD. When the multiple logistic analysis was repeated with a stepwise procedure, only apo A-I and B entered into the model. The results of our study indicate that plasma levels of apo A-I and B are more useful than plasma lipid in detecting the presence or absence of coronary artery disease in a group of male patients undergoing coronary angiography. FAU - Marcovina, S AU - Marcovina S AD - Laboratori di Immunochimica e Lipoproteine, Istituto Scientifico Ospedale San Raffaele, Milano. FAU - Zoppo, A AU - Zoppo A FAU - Graziani, M S AU - Graziani MS FAU - Vassanelli, C AU - Vassanelli C FAU - Catapano, A L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Italy TA - Ric Clin Lab JT - La Ricerca in clinica e in laboratorio JID - 7613947 RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins A) RN - 0 (Apolipoproteins B) RN - 0 (Cholesterol, HDL) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adult MH - Aged MH - Apolipoprotein A-I MH - Apolipoproteins A/*blood MH - Apolipoproteins B/*blood MH - Cholesterol/blood MH - Cholesterol, HDL/blood MH - Coronary Angiography MH - Coronary Disease/*blood/diagnostic imaging/pathology MH - Coronary Vessels/pathology MH - Humans MH - Male MH - Middle Aged MH - Risk Factors MH - Triglycerides/blood EDAT- 1988/10/01 00:00 MHDA- 1988/10/01 00:01 CRDT- 1988/10/01 00:00 PHST- 1988/10/01 00:00 [pubmed] PHST- 1988/10/01 00:01 [medline] PHST- 1988/10/01 00:00 [entrez] PST - ppublish SO - Ric Clin Lab. 1988 Oct-Dec;18(4):319-28. PMID- 3171393 OWN - NLM STAT- MEDLINE DCOM- 19881122 LR - 20061115 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 29 IP - 6 DP - 1988 Jun TI - Apolipoprotein C-II deficiency: detection of immunoreactive apolipoprotein C-II in the intestinal mucosa of two patients. PG - 703-11 AB - Recent data suggest that mutant immunoreactive forms of apolipoprotein C-II (apoC-II) can be detected in the plasma of patients with the apoC-II deficiency syndrome. We studied the possible presence of apoC-II mutants in the plasma of two patients with apoC-II deficiency by immunological means. The patients were hypertriglyceridemic, and apoC-II was undetectable in plasma as determined by radial immunodiffusion, electroimmunoassay, and immunonephelometry. Furthermore, apoC-II was undetectable either by electrophoresis or by immunoblotting in the plasma of the probands, while apoC-II was present in the plasma of their parents, although at less than half-normal concentration. Immunochemical localization of apoC-II, however, showed that the apoprotein could be detected within the enterocytes obtained from the intestinal mucosa of the patients. From these data we conclude that the patients synthesize apoC-II, at least in the intestine. FAU - Capurso, A AU - Capurso A AD - Istituto di Clinica Medica II, Universita di Bari, Italy. FAU - Mogavero, A M AU - Mogavero AM FAU - Resta, F AU - Resta F FAU - Di Tommaso, M AU - Di Tommaso M FAU - Taverniti, P AU - Taverniti P FAU - Turturro, F AU - Turturro F FAU - La Rosa, M AU - La Rosa M FAU - Marcovina, S AU - Marcovina S FAU - Catapano, A L AU - Catapano AL LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoproteins C) SB - IM MH - Apolipoprotein C-II MH - Apolipoproteins C/*deficiency/immunology/isolation & purification MH - Child MH - Electrophoresis, Polyacrylamide Gel MH - Female MH - Humans MH - Immunochemistry MH - Intestinal Mucosa/*analysis MH - Isoelectric Focusing MH - Male MH - Mutation MH - Nephelometry and Turbidimetry EDAT- 1988/06/01 00:00 MHDA- 1988/06/01 00:01 CRDT- 1988/06/01 00:00 PHST- 1988/06/01 00:00 [pubmed] PHST- 1988/06/01 00:01 [medline] PHST- 1988/06/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1988 Jun;29(6):703-11. PMID- 3446410 OWN - NLM STAT- MEDLINE DCOM- 19880517 LR - 20171223 IS - 0009-3084 (Print) IS - 0009-3084 (Linking) VI - 45 IP - 1 DP - 1987 Oct TI - Activation of lipoprotein lipase by apolipoprotein C-II is modulated by the COOH terminal region of apolipoprotein C-III. PG - 39-47 AB - The in vitro effect of apolipoprotein C-II (apo C-II) on the apolipoprotein C-III (apo C-III) induced activation of bovine milk lipoprotein lipase (LPL) was studied in vitro using a synthetic substrate. Apo C-III effectively inhibited, in a dose-dependent manner, the activation of lipoprotein lipase induced by apo C-II. A 3-fold molar apo C-III excess decreased the lipoprotein lipase activity by 25%. Thrombin cleavage of apo C-III produced two fragments: only fragment 41-79 retained the inhibitory activity and was equipotent to native apo C-III1 on a molar basis. Neither displacement of apo C-II from the substrate, as determined using 125I-labeled apo C-II, nor the charge carried by sialic residues of apo C-III, as demonstrated in experiments performed after neuraminidase treatment, accounted for this effect. I speculate that apo C-III may act by inhibiting the apo C-II-LPL interaction. FAU - Catapano, A L AU - Catapano AL AD - Institute of Pharmacological Sciences, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Chem Phys Lipids JT - Chemistry and physics of lipids JID - 0067206 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoprotein C-III) RN - 0 (Apolipoproteins C) RN - 0 (Peptide Fragments) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Animals MH - Apolipoprotein C-II MH - Apolipoprotein C-III MH - Apolipoproteins C/metabolism/*pharmacology MH - Cattle MH - Enzyme Activation MH - Female MH - Kinetics MH - Lipoprotein Lipase/*metabolism MH - Milk/*enzymology MH - Peptide Fragments/metabolism/pharmacology MH - Protein Binding EDAT- 1987/10/01 00:00 MHDA- 1987/10/01 00:01 CRDT- 1987/10/01 00:00 PHST- 1987/10/01 00:00 [pubmed] PHST- 1987/10/01 00:01 [medline] PHST- 1987/10/01 00:00 [entrez] AID - 0009-3084(87)90038-7 [pii] PST - ppublish SO - Chem Phys Lipids. 1987 Oct;45(1):39-47. PMID- 3109219 OWN - NLM STAT- MEDLINE DCOM- 19870716 LR - 20161109 IS - 0065-2598 (Print) IS - 0065-2598 (Linking) VI - 210 DP - 1987 TI - Use of combined monoclonal antibodies for the immunochemical determination of apolipoproteins A-I and B in human plasma. PG - 63-71 FAU - Marcovina, S AU - Marcovina S FAU - Catapano, A L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Adv Exp Med Biol JT - Advances in experimental medicine and biology JID - 0121103 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins A) RN - 0 (Apolipoproteins B) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) SB - IM MH - Animals MH - *Antibodies, Monoclonal/isolation & purification MH - Apolipoprotein A-I MH - Apolipoproteins A/*blood/immunology MH - Apolipoproteins B/*blood/immunology MH - Humans MH - Immunoassay MH - Immunodiffusion MH - Lipoproteins, LDL/immunology MH - Lipoproteins, VLDL/immunology MH - Male MH - Mice MH - Precipitin Tests/methods EDAT- 1987/01/01 00:00 MHDA- 1987/01/01 00:01 CRDT- 1987/01/01 00:00 PHST- 1987/01/01 00:00 [pubmed] PHST- 1987/01/01 00:01 [medline] PHST- 1987/01/01 00:00 [entrez] PST - ppublish SO - Adv Exp Med Biol. 1987;210:63-71. PMID- 3549954 OWN - NLM STAT- MEDLINE DCOM- 19870520 LR - 20131121 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 28 IP - 1 DP - 1987 Jan TI - A dot-blot assay for the low density lipoprotein receptor. PG - 108-12 AB - We describe a new method for detecting the interaction of low density lipoprotein with its receptor using unmodified nitrocellulose as support for membrane protein. The method is specific and sensitive down to 3 micrograms of membrane protein. Unlabeled LDL, but not HDL, competes with 125I-labeled LDL for binding, and binding is abolished by pretreatment of the membranes with pronase and is dependent upon the presence of Ca2+. Furthermore, modification of arginine or lysine residues on LDL abolishes the lipoprotein interaction with the receptor protein supported on the nitrocellulose. When the membranes are solubilized with octyl glucoside, purification steps of the receptor can be directly followed with no interference of the detergent, therefore eliminating the need for its removal. The increased expression of LDL receptors on liver membranes from estradiol-treated rats was also demonstrated. We suggest, therefore, that this method can be used to detect the presence of LDL receptors on minute amounts of membrane protein. FAU - Maggi, F M AU - Maggi FM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Iodine Radioisotopes) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) RN - SY7Q814VUP (Calcium) SB - IM MH - Adrenal Cortex/*metabolism MH - Animals MH - Binding, Competitive MH - Calcium/pharmacology MH - Cattle MH - Cell Membrane/metabolism MH - Humans MH - Iodine Radioisotopes MH - Kinetics MH - Lipoproteins, LDL/metabolism MH - Radioisotope Dilution Technique MH - Receptors, LDL/*metabolism EDAT- 1987/01/01 00:00 MHDA- 1987/01/01 00:01 CRDT- 1987/01/01 00:00 PHST- 1987/01/01 00:00 [pubmed] PHST- 1987/01/01 00:01 [medline] PHST- 1987/01/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1987 Jan;28(1):108-12. PMID- 3096610 OWN - NLM STAT- MEDLINE DCOM- 19870112 LR - 20061115 IS - 0009-9147 (Print) IS - 0009-9147 (Linking) VI - 32 IP - 12 DP - 1986 Dec TI - Radial-immunodiffusion assay of human apolipoprotein A-I with use of two monoclonal antibodies combined. PG - 2155-9 AB - We produced and characterized several monoclonal antibodies directed toward human plasma apolipoprotein A-I. Two of them, A-I-12 and A-I-57, individually precipitated purified or native high-density lipoprotein in agarose gel by double immunodiffusion. Because radial immunodiffusion performed with a single monoclonal antibody gave faint and diffuse rings of precipitation, we developed and optimized working conditions for using these two monoclonal antibodies combined to determine apolipoprotein A-I in human plasma. This combination gave easy-to-measure, clear, sharp rings, and linear and parallel standard curves for HDL3 (the primary standard) and a reference serum (the secondary standard). Moreover, no pretreatment of samples with dissociating agents or detergents is necessary. The assay was complete after overnight incubation, as compared with two to three days when polyclonal antisera were used. Apolipoprotein A-I concentrations as measured in 128 normolipidemic subjects and in 72 patients with various lipid disorders by the radial immunodiffusion technique with monoclonal antibodies (x) compared well (r = 0.882; y = 1.029x-0.036) with those measured by radial immunodiffusion with polyclonal antisera (y). FAU - Marcovina, S AU - Marcovina S FAU - Di Cola, G AU - Di Cola G FAU - Catapano, A L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Chem JT - Clinical chemistry JID - 9421549 RN - 0 (Antibodies, Monoclonal) RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins A) RN - 0 (Immune Sera) SB - IM MH - Antibodies, Monoclonal MH - Apolipoprotein A-I MH - Apolipoproteins A/*blood/immunology MH - Humans MH - Immune Sera MH - Immunodiffusion/methods MH - Reference Standards EDAT- 1986/12/01 00:00 MHDA- 1986/12/01 00:01 CRDT- 1986/12/01 00:00 PHST- 1986/12/01 00:00 [pubmed] PHST- 1986/12/01 00:01 [medline] PHST- 1986/12/01 00:00 [entrez] PST - ppublish SO - Clin Chem. 1986 Dec;32(12):2155-9. PMID- 3021510 OWN - NLM STAT- MEDLINE DCOM- 19861126 LR - 20181113 IS - 0014-4754 (Print) IS - 0014-4754 (Linking) VI - 42 IP - 10 DP - 1986 Oct 15 TI - Cholesterol feeding to rats does not modulate the expression of binding sites for HDL on liver membranes. PG - 1155-7 AB - The binding of HDL, Apo-E-free, was studied in rats fed a cholesterol rich diet for 2, 4 and 7 days. Plasma cholesterol increased up to 16-fold (from 55 to 900 mg/dl); liver cholesterol was also raised, from 0.5 to 16 mg/g of tissue. The HDL binding to membrane preparations was not affected while the binding of beta VLDL was reduced to about 50% of the controls. These data show, therefore, that liver binding sites for HDL are refractory to regulation by dietary cholesterol. FAU - Maggi, F M AU - Maggi FM FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Experientia JT - Experientia JID - 0376547 RN - 0 (Carrier Proteins) RN - 0 (Cholesterol, Dietary) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (RNA-Binding Proteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Lipoprotein) RN - 0 (high density lipoprotein receptors) RN - 147605-06-9 (high density lipoprotein binding protein) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - *Carrier Proteins MH - Cell Membrane/metabolism MH - Cholesterol/blood/metabolism MH - Cholesterol, Dietary/*pharmacology MH - Lipoproteins, HDL/*metabolism MH - Lipoproteins, VLDL/metabolism MH - Liver/drug effects/*metabolism MH - Male MH - *RNA-Binding Proteins MH - Rats MH - Receptors, Cell Surface/drug effects/metabolism MH - *Receptors, Lipoprotein EDAT- 1986/10/15 00:00 MHDA- 1986/10/15 00:01 CRDT- 1986/10/15 00:00 PHST- 1986/10/15 00:00 [pubmed] PHST- 1986/10/15 00:01 [medline] PHST- 1986/10/15 00:00 [entrez] PST - ppublish SO - Experientia. 1986 Oct 15;42(10):1155-7. PMID- 3760193 OWN - NLM STAT- MEDLINE DCOM- 19861107 LR - 20181113 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 78 IP - 4 DP - 1986 Oct TI - Autoantibodies to the low density lipoprotein receptor in a subject affected by severe hypercholesterolemia. PG - 940-6 AB - We studied a 32-yr-old man with a benign paraproteinemia (IgA) affected by severe nonfamilial hypercholesterolemia. In vitro experiments demonstrated that lipoprotein-deficient serum (LPDS) from the patient inhibited the binding of low density lipoprotein (LDL) to human skin fibroblasts cultured in vitro (up to 70%) whereas LPDS from controls had no effect. Removal of IgA from the patient's serum by immunoprecipitation with mono-specific antisera abolished the inhibition of LDL binding. IgA isolated from the serum of the patient by affinity chromatography inhibited, in a dose-dependent manner, the binding of LDL to human skin fibroblasts in vitro, thus showing an IgA-mediated effect. Ligand-blotting experiments demonstrated that the paraprotein directly interacts with the LDL receptor, thus inhibiting the binding of the lipoprotein. Treatment of the receptor protein with reducing agents blocked the interaction of the antibody with the LDL receptor. From these data we speculate that this autoantibody may be responsible for the severe nonfamilial hypercholesterolemia of the patient. FAU - Corsini, A AU - Corsini A FAU - Roma, P AU - Roma P FAU - Sommariva, D AU - Sommariva D FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Apolipoproteins E) RN - 0 (Autoantibodies) RN - 0 (Immunoglobulin A) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, HDL3) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, LDL) SB - AIM SB - IM MH - Adult MH - Apolipoproteins E MH - Autoantibodies/*analysis MH - Binding, Competitive MH - Chromatography, Affinity MH - Humans MH - Hypercholesterolemia/*immunology MH - Immunoglobulin A/analysis MH - Lipoproteins, HDL/metabolism MH - Lipoproteins, HDL3 MH - Lipoproteins, LDL/metabolism MH - Male MH - Receptors, LDL/*immunology PMC - PMC423724 EDAT- 1986/10/01 00:00 MHDA- 1986/10/01 00:01 CRDT- 1986/10/01 00:00 PHST- 1986/10/01 00:00 [pubmed] PHST- 1986/10/01 00:01 [medline] PHST- 1986/10/01 00:00 [entrez] AID - 10.1172/JCI112684 [doi] PST - ppublish SO - J Clin Invest. 1986 Oct;78(4):940-6. doi: 10.1172/JCI112684. PMID- 3964353 OWN - NLM STAT- MEDLINE DCOM- 19860507 LR - 20131121 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 59 IP - 3 DP - 1986 Mar TI - Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver. PG - 329-33 AB - The effect of experimental hypothyroidism on the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using [125I]LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hypothyroid rats and with the demonstration, by ligand blotting analysis, of a decreased expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver. FAU - Scarabottolo, L AU - Scarabottolo L FAU - Trezzi, E AU - Trezzi E FAU - Roma, P AU - Roma P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Receptors, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Cholesterol/blood MH - Hypothyroidism/etiology/*metabolism MH - Kinetics MH - Lipoproteins/blood MH - Lipoproteins, LDL/metabolism MH - Lipoproteins, VLDL/metabolism MH - Liver/*metabolism MH - Male MH - Rats MH - Rats, Inbred Strains MH - Receptors, LDL/*metabolism MH - Thyroidectomy EDAT- 1986/03/01 00:00 MHDA- 1986/03/01 00:01 CRDT- 1986/03/01 00:00 PHST- 1986/03/01 00:00 [pubmed] PHST- 1986/03/01 00:01 [medline] PHST- 1986/03/01 00:00 [entrez] AID - 0021-9150(86)90129-2 [pii] PST - ppublish SO - Atherosclerosis. 1986 Mar;59(3):329-33. PMID- 3541526 OWN - NLM STAT- MEDLINE DCOM- 19870205 LR - 20161109 IS - 0065-2598 (Print) IS - 0065-2598 (Linking) VI - 201 DP - 1986 TI - A family study of hypoalphalipoproteinemia. PG - 93-103 FAU - Vergani, C AU - Vergani C FAU - Catapano, A L AU - Catapano AL FAU - Sidoli, A AU - Sidoli A LA - eng PT - Journal Article PT - Review PL - United States TA - Adv Exp Med Biol JT - Advances in experimental medicine and biology JID - 0121103 RN - 0 (Apolipoproteins) RN - 0 (Cholesterol, HDL) SB - IM MH - Adult MH - Apolipoproteins/blood MH - Cholesterol, HDL/blood MH - Humans MH - Hypolipoproteinemias/*genetics MH - Immunoelectrophoresis MH - Microscopy, Electron MH - Pedigree MH - Tangier Disease/genetics RF - 20 EDAT- 1986/01/01 00:00 MHDA- 1986/01/01 00:01 CRDT- 1986/01/01 00:00 PHST- 1986/01/01 00:00 [pubmed] PHST- 1986/01/01 00:01 [medline] PHST- 1986/01/01 00:00 [entrez] PST - ppublish SO - Adv Exp Med Biol. 1986;201:93-103. PMID- 3736556 OWN - NLM STAT- MEDLINE DCOM- 19860916 LR - 20061115 IS - 0077-099X (Print) IS - 0077-099X (Linking) VI - 14 DP - 1986 TI - Bile lipids, platelet aggregability and pro-ApoAI processing in 2 cases of Tangier disease. PG - 154-8 FAU - Catapano, A L AU - Catapano AL FAU - Giudici, G AU - Giudici G FAU - Roma, P AU - Roma P FAU - Vergani, C G AU - Vergani CG LA - eng PT - Case Reports PT - Journal Article PL - Switzerland TA - Monogr Atheroscler JT - Monographs on atherosclerosis JID - 0362400 RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins A) RN - 0 (Lipids) RN - 0 (Protein Precursors) RN - 54397-85-2 (Thromboxane B2) SB - IM MH - Apolipoprotein A-I MH - Apolipoproteins A/*metabolism MH - Bile/*analysis MH - Blood Platelets/metabolism MH - Humans MH - Hypolipoproteinemias/*metabolism MH - Lipids/*analysis MH - Male MH - Middle Aged MH - *Platelet Aggregation MH - Protein Precursors/*metabolism MH - Tangier Disease/blood/*metabolism MH - Thromboxane B2/biosynthesis EDAT- 1986/01/01 00:00 MHDA- 1986/01/01 00:01 CRDT- 1986/01/01 00:00 PHST- 1986/01/01 00:00 [pubmed] PHST- 1986/01/01 00:01 [medline] PHST- 1986/01/01 00:00 [entrez] PST - ppublish SO - Monogr Atheroscler. 1986;14:154-8. PMID- 6095991 OWN - NLM STAT- MEDLINE DCOM- 19850221 LR - 20170907 IS - 0304-3835 (Print) IS - 0304-3835 (Linking) VI - 25 IP - 2 DP - 1984 Dec TI - In vivo assimilation of low density lipoproteins by a fibrosarcoma tumour line in mice. PG - 203-8 AB - A tumour line inoculated in mice showed high affinity binding for lipoproteins in vitro. Studies in vivo demonstrated that the assimilation of human low density lipoprotein (LDL) by the tumour was very high. Both receptor and non-receptor mediated catabolism of the lipoprotein by the tumour increased as compared to other tissues known to be sites of lipoprotein catabolism (liver, spleen etc.). These findings suggest that lipoproteins may be useful markers for tumours as well as carriers for cytotoxic drugs to target tissues in vivo. FAU - Norata, G AU - Norata G FAU - Canti, G AU - Canti G FAU - Ricci, L AU - Ricci L FAU - Nicolin, A AU - Nicolin A FAU - Trezzi, E AU - Trezzi E FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Lipoprotein) SB - IM MH - Animals MH - Binding Sites MH - Cell Line MH - Fibrosarcoma/*metabolism/pathology MH - Humans MH - Lipoproteins/metabolism MH - Lipoproteins, LDL/*metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Neoplasm Transplantation MH - Receptors, Cell Surface/metabolism MH - Receptors, Lipoprotein EDAT- 1984/12/01 00:00 MHDA- 1984/12/01 00:01 CRDT- 1984/12/01 00:00 PHST- 1984/12/01 00:00 [pubmed] PHST- 1984/12/01 00:01 [medline] PHST- 1984/12/01 00:00 [entrez] AID - S0304-3835(84)80046-4 [pii] PST - ppublish SO - Cancer Lett. 1984 Dec;25(2):203-8. PMID- 6093829 OWN - NLM STAT- MEDLINE DCOM- 19841217 LR - 20141120 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 52 IP - 3 DP - 1984 Sep TI - Effects of probucol on the in vivo plasma clearance of human low density lipoproteins in rabbits and on the expression of lipoprotein receptors in vitro. PG - 309-16 AB - The purpose of this study was to investigate the effects of probucol on the plasma levels of low density lipoproteins in rabbits and whether the resulting decrease of low density lipoproteins was related to the effects of probucol on the expression of lipoprotein receptors. Probucol administration effectively lowered plasma cholesterol in normal rabbits. Both low density and high density lipoprotein cholesterol decreased, as well as apo B in the former fraction. Probucol had no effect on the fractional catabolic rate of low density lipoprotein while the flux of this lipoprotein decreased to about 50%. Moreover both the binding of lipoproteins to liver membranes and the in vitro uptake of low density lipoprotein by human skin fibroblasts were not affected by the drug. These findings are consistent with an effect of probucol on low density lipoprotein synthesis. FAU - Trezzi, E AU - Trezzi E FAU - Roma, P AU - Roma P FAU - Bernini, F AU - Bernini F FAU - Fumagalli, R AU - Fumagalli R FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Phenols) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Lipoprotein) RN - 97C5T2UQ7J (Cholesterol) RN - P3CTH044XJ (Probucol) SB - IM MH - Animals MH - Cholesterol/blood MH - Fibroblasts/metabolism MH - Humans MH - In Vitro Techniques MH - Kinetics MH - Lipoproteins, HDL/blood MH - Lipoproteins, LDL/*blood MH - Lipoproteins, VLDL/blood MH - Liver/metabolism MH - Male MH - Phenols/*pharmacology MH - Probucol/*pharmacology MH - Rabbits MH - Receptors, Cell Surface/*metabolism MH - Receptors, Lipoprotein EDAT- 1984/09/01 00:00 MHDA- 1984/09/01 00:01 CRDT- 1984/09/01 00:00 PHST- 1984/09/01 00:00 [pubmed] PHST- 1984/09/01 00:01 [medline] PHST- 1984/09/01 00:00 [entrez] AID - 0021-9150(84)90061-3 [pii] PST - ppublish SO - Atherosclerosis. 1984 Sep;52(3):309-16. PMID- 6432845 OWN - NLM STAT- MEDLINE DCOM- 19841024 LR - 20181113 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 74 IP - 3 DP - 1984 Sep TI - Comparative in vitro study of the pro-apolipoprotein A-I to apolipoprotein A-I converting activity between normal and Tangier plasma. PG - 1098-103 AB - We examined the ability of the plasma of a 52-yr-old male Tangier patient to effect the conversion of radiolabeled pro-apolipoprotein A-I (apo A-I), isolated from hepatoma cell culture media, into mature apo A-I. The conversion was assessed by amino-terminal sequence analysis, isoform patterns with two-dimensional gel electrophoresis, and a rapid assay based on the different solubilities of intact pro-apo A-I and its hexapeptide prosegment in 10% trichloroacetic acid. We found that the converting activity of Tangier plasma was comparable to that exhibited by control normolipidemic plasma and that in both cases pro-apo A-I was correctly processed at the Gln-Asp bond. After ultracentrifugal fractionation of Tangier plasma at d = 1.21 g/ml, the pro-apo A-I-to-mature apo A-I converting activity was mainly recovered in the middle fraction of d = 1.225 g/ml and was at least 10-fold more effective than the top and bottom fractions. In contrast, in normal plasma the activity was only present in the top and bottom fractions. It has been previously established that in Tangier plasma the pro-apo A-I/apo A-I ratio is significantly higher than normal (1 vs. 0.02). Our studies suggest that this abnormal ratio is not the result of a reduced converting enzyme activity and may relate to differences in turnover rates between Tangier and normal plasma apolipoproteins. FAU - Edelstein, C AU - Edelstein C FAU - Gordon, J I AU - Gordon JI FAU - Vergani, C A AU - Vergani CA FAU - Catapano, A L AU - Catapano AL FAU - Pietrini, V AU - Pietrini V FAU - Scanu, A M AU - Scanu AM LA - eng GR - AM-30292/AM/NIADDK NIH HHS/United States GR - HL-18577/HL/NHLBI NIH HHS/United States PT - Case Reports PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins A) RN - 0 (Apolipoproteins B) RN - 0 (Lipids) RN - 0 (Lipoproteins, HDL) RN - 0 (Protein Precursors) RN - 0 (apolipoprotein A-I Tangier) SB - AIM SB - IM MH - Amino Acid Sequence MH - Apolipoprotein A-I MH - Apolipoproteins/biosynthesis/*blood MH - *Apolipoproteins A MH - Apolipoproteins B MH - Electrophoresis, Polyacrylamide Gel MH - Humans MH - Hypolipoproteinemias/*blood MH - Isoelectric Focusing MH - Lipids/blood MH - Lipoproteins, HDL/*blood MH - Male MH - Middle Aged MH - Protein Precursors/*blood MH - Reference Values MH - Tangier Disease/*blood PMC - PMC425269 EDAT- 1984/09/01 00:00 MHDA- 1984/09/01 00:01 CRDT- 1984/09/01 00:00 PHST- 1984/09/01 00:00 [pubmed] PHST- 1984/09/01 00:01 [medline] PHST- 1984/09/01 00:00 [entrez] AID - 10.1172/JCI111477 [doi] PST - ppublish SO - J Clin Invest. 1984 Sep;74(3):1098-103. doi: 10.1172/JCI111477. PMID- 6087380 OWN - NLM STAT- MEDLINE DCOM- 19840824 LR - 20131121 IS - 0031-6989 (Print) IS - 0031-6989 (Linking) VI - 16 IP - 6 DP - 1984 Jun TI - Effects of insulin deficiency on the catabolism of plasma lipoproteins and on the expression of hepatic lipoprotein receptors in rats. PG - 539-48 AB - The effect of insulin deficiency on the expression of lipoprotein receptors by the liver and on the in vivo catabolism of plasma lipoproteins was investigated in rats made insulin deficient by an I.V. injection of streptozotocin. The binding of beta very low density lipoprotein to liver membranes was not affected by insulin deficiency, furthermore the in vivo catabolism of beta very low density lipoproteins and low density lipoprotein in diabetic rats was similar to that of controls. These data suggest that insulin deficiency neither modulates the expression of receptors for lipoproteins by the liver nor the in vivo catabolism of lipoproteins such as beta very low density and low density lipoproteins which are removed from the plasma, at least in part, by receptor mediated processes. FAU - Trezzi, E AU - Trezzi E FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pharmacol Res Commun JT - Pharmacological research communications JID - 0236354 RN - 0 (Blood Glucose) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Lipoprotein) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Blood Glucose/metabolism MH - Cell Membrane/metabolism MH - Cholesterol/blood MH - Diabetes Mellitus, Experimental/blood/*metabolism MH - Lipoproteins/*blood MH - Lipoproteins, LDL/blood MH - Lipoproteins, VLDL/blood MH - Liver/*metabolism/ultrastructure MH - Male MH - Rats MH - Rats, Inbred Strains MH - Receptors, Cell Surface/*metabolism MH - Receptors, Lipoprotein MH - Triglycerides/blood EDAT- 1984/06/01 00:00 MHDA- 1984/06/01 00:01 CRDT- 1984/06/01 00:00 PHST- 1984/06/01 00:00 [pubmed] PHST- 1984/06/01 00:01 [medline] PHST- 1984/06/01 00:00 [entrez] PST - ppublish SO - Pharmacol Res Commun. 1984 Jun;16(6):539-48. PMID- 6421598 OWN - NLM STAT- MEDLINE DCOM- 19840425 LR - 20131121 IS - 0014-2972 (Print) IS - 0014-2972 (Linking) VI - 14 IP - 1 DP - 1984 Feb TI - Bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (Tangier disease). PG - 49-54 AB - A 62-year-old man with clinical and biochemical findings consistent with homozygous Tangier disease is presented. Widespread atherosclerosis was present. Bile lipid analysis showed a low molar percentage of cholesterol with a low saturation index. The data suggest that high density lipoprotein cholesterol may act as a preferential precursor of biliary cholesterol. Coagulation and platelet studies indicated that the patient's platelets were hyper-responsive to aggregating agents and produced an increased amount of thromboxane B2. A platelet storage pool deficiency was also found. FAU - Vergani, C G AU - Vergani CG FAU - Plancher, A C AU - Plancher AC FAU - Zuin, M AU - Zuin M FAU - Cattaneo, M AU - Cattaneo M FAU - Tramaloni, C AU - Tramaloni C FAU - Maccari, S AU - Maccari S FAU - Roma, P AU - Roma P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Case Reports PT - Journal Article PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins) RN - 0 (Bile Acids and Salts) RN - 0 (Cholesterol, HDL) RN - 0 (Lipids) RN - 0 (Lipoproteins, HDL) RN - 333DO1RDJY (Serotonin) RN - 54397-85-2 (Thromboxane B2) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Aged MH - Apolipoprotein A-I MH - Apolipoproteins/blood MH - Bile/*analysis MH - Bile Acids and Salts/analysis MH - Blood Coagulation Disorders/*blood/complications MH - Blood Platelet Disorders/*blood/complications MH - Cholesterol/analysis/blood MH - Cholesterol, HDL MH - Humans MH - Hypolipoproteinemias/*metabolism MH - Lipids/*analysis MH - Lipoproteins, HDL/analysis/blood MH - Male MH - Middle Aged MH - Serotonin/blood MH - Tangier Disease/blood/complications/*metabolism MH - Thromboxane B2/blood EDAT- 1984/02/01 00:00 MHDA- 1984/02/01 00:01 CRDT- 1984/02/01 00:00 PHST- 1984/02/01 00:00 [pubmed] PHST- 1984/02/01 00:01 [medline] PHST- 1984/02/01 00:00 [entrez] PST - ppublish SO - Eur J Clin Invest. 1984 Feb;14(1):49-54. PMID- 6091429 OWN - NLM STAT- MEDLINE DCOM- 19841121 LR - 20151119 IS - 0379-0363 (Print) IS - 0379-0363 (Linking) VI - 16 DP - 1984 TI - A saturable binding site for high density lipoprotein3 on human liver membranes. PG - 47-51 AB - The binding of High Density Lipoprotein3 (HDL) to human liver membranes obtained from male normolipemic subjects was studied. High Density Lipoprotein3 binds in a specific, saturable manner to liver membranes; furthermore, this binding site appears to be distinct from these previously described for Low Density Lipoprotein (LDL) and chylomicron remnants. Competition experiments using Apo A-I reconstituted lipoproteins suggest that Apo A-I could be the determinant of the binding. FAU - Trezzi, E AU - Trezzi E FAU - Maggi, F M AU - Maggi FM FAU - Maione, G AU - Maione G FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Agents Actions Suppl JT - Agents and actions. Supplements JID - 7801014 RN - 0 (Apolipoprotein A-I) RN - 0 (Apolipoproteins A) RN - 0 (Iodine Radioisotopes) RN - 0 (Lipids) RN - 0 (Lipoproteins, HDL) RN - 0 (Low Density Lipoprotein Receptor-Related Protein-1) RN - 0 (Receptors, Cell Surface) SB - IM MH - Apolipoprotein A-I MH - Apolipoproteins A/metabolism MH - Binding Sites MH - Humans MH - In Vitro Techniques MH - Iodine Radioisotopes MH - Kinetics MH - Lipids/blood MH - Lipoproteins, HDL/*metabolism MH - Liver/*metabolism MH - Low Density Lipoprotein Receptor-Related Protein-1 MH - Male MH - Membranes/metabolism MH - Receptors, Cell Surface/metabolism EDAT- 1984/01/01 00:00 MHDA- 1984/01/01 00:01 CRDT- 1984/01/01 00:00 PHST- 1984/01/01 00:00 [pubmed] PHST- 1984/01/01 00:01 [medline] PHST- 1984/01/01 00:00 [entrez] PST - ppublish SO - Agents Actions Suppl. 1984;16:47-51. PMID- 6872264 OWN - NLM STAT- MEDLINE DCOM- 19830920 LR - 20171128 IS - 0009-8981 (Print) IS - 0009-8981 (Linking) VI - 130 IP - 3 DP - 1983 Jun 15 TI - Plasma lipids, lipoproteins and apoproteins in a case of apo C-II deficiency. PG - 317-27 AB - A new case of apo C-II deficiency is described. The patient had plasma triglyceride levels ranging from 10.2-30.5 mmol/l. Apo C-II deficiency was confirmed by gel electrophoresis, isoelectric focusing and immunochemistry. In this patient plasma lipoproteins were mainly chylomicrons and very low density lipoproteins, LDL and HDL levels being very low. Infusion of normal plasma effectively reduced plasma triglycerides and enhanced low density and high density lipoproteins cholesterol levels. These data suggest that in vivo a precursor-product relationship exists between triglyceride rich lipoproteins and LDL and HDL, and further stress the role of the lipoprotein lipase-apo C-II system in modulating these metabolic interconversions. FAU - Catapano, A L AU - Catapano AL FAU - Mills, G L AU - Mills GL FAU - Roma, P AU - Roma P FAU - La Rosa, M AU - La Rosa M FAU - Capurso, A AU - Capurso A LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Clin Chim Acta JT - Clinica chimica acta; international journal of clinical chemistry JID - 1302422 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins C) RN - 0 (Apoproteins) RN - 0 (Chylomicrons) RN - 0 (Lipids) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Apolipoprotein C-II MH - Apolipoproteins/*deficiency MH - *Apolipoproteins C MH - Apoproteins/*blood MH - Child MH - Cholesterol/blood MH - Chylomicrons/blood MH - Female MH - Humans MH - Lipids/*blood MH - Lipoprotein Lipase/metabolism MH - Lipoproteins/*blood MH - Lipoproteins, HDL/blood MH - Lipoproteins, LDL/blood MH - Triglycerides/blood EDAT- 1983/06/15 00:00 MHDA- 1983/06/15 00:01 CRDT- 1983/06/15 00:00 PHST- 1983/06/15 00:00 [pubmed] PHST- 1983/06/15 00:01 [medline] PHST- 1983/06/15 00:00 [entrez] AID - 0009-8981(83)90306-6 [pii] PST - ppublish SO - Clin Chim Acta. 1983 Jun 15;130(3):317-27. PMID- 6886567 OWN - NLM STAT- MEDLINE DCOM- 19831021 LR - 20131121 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 24 IP - 6 DP - 1983 Jun TI - Subfractionation of human very low density lipoproteins by heparin-Sepharose affinity chromatography. PG - 790-5 AB - Very low density lipoproteins obtained from normolipidemic subjects were fractionated into subclasses by means of affinity chromatography on a heparin-Sepharose column in the presence of MnCl2. The four subfractions eluted at 0.05, 0.12, 0.20, and 0.38 M NaCl and they differed in chemical composition and apoprotein pattern. The relative amounts of apoB and apoE in subfractions increased with increasing concentrations of the NaCl eluant. Modification of the arginyl residues with 1-2 cyclohexadione demonstrated that arginine plays an important role in determining the elution pattern of VLDL. In vitro studies indicated that only fractions eluted at 0.2 and 0.5 M NaCl compete with LDL for cellular receptors. These data suggest that the various subfractions may represent VLDL at different stages of catabolism. FAU - Trezzi, E AU - Trezzi E FAU - Calvi, C AU - Calvi C FAU - Roma, P AU - Roma P FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Cholesterol Esters) RN - 0 (Lipoproteins, VLDL) RN - 0 (Phospholipids) RN - 0 (Triglycerides) RN - 0 (heparin-sepharose) RN - 9012-36-6 (Sepharose) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Cholesterol/analysis MH - Cholesterol Esters/analysis MH - Chromatography, Affinity MH - Humans MH - Lipoproteins, VLDL/blood/*isolation & purification MH - Phospholipids/analysis MH - Sepharose/analogs & derivatives MH - Triglycerides/analysis EDAT- 1983/06/01 00:00 MHDA- 1983/06/01 00:01 CRDT- 1983/06/01 00:00 PHST- 1983/06/01 00:00 [pubmed] PHST- 1983/06/01 00:01 [medline] PHST- 1983/06/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1983 Jun;24(6):790-5. PMID- 6847743 OWN - NLM STAT- MEDLINE DCOM- 19830610 LR - 20141120 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 46 IP - 3 DP - 1983 Mar TI - Effect of partial ileal bypass on plasma clearance and binding of lipoproteins to liver membranes in the rabbit. PG - 269-73 AB - We studied the effect of partial ileal bypass in the rabbit on the in vivo catabolism of human 125I-labelled low density lipoproteins and on the in vitro binding of human low density lipoproteins and rabbit very low density lipoproteins to hepatic membrane preparations. The in vivo data indicate that partial ileal bypass increases the fractional clearance rate (pools/h) of low density lipoproteins from 0.031 to 0.049 as well as the absolute catabolic rate from 0.495 to 0.605 mg/h. Concomitantly the in vitro binding of both low and very low density lipoproteins to hepatic membranes was increased in membrane preparation from livers of bypassed animals, thus suggesting an increased receptor-mediated uptake of lipoproteins by the liver. This effect may partly explain the hypocholesterolemic activity of partial ileal by-pass. FAU - Trezzi, E AU - Trezzi E FAU - Maione, G AU - Maione G FAU - Fox, U AU - Fox U FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Cholesterol/blood MH - Cholesterol, HDL MH - Cholesterol, LDL MH - Ileum/*surgery MH - In Vitro Techniques MH - Lipoproteins, HDL/blood MH - Lipoproteins, LDL/blood/*metabolism MH - Lipoproteins, VLDL/*metabolism MH - Liver/*metabolism MH - Male MH - Rabbits EDAT- 1983/03/01 00:00 MHDA- 1983/03/01 00:01 CRDT- 1983/03/01 00:00 PHST- 1983/03/01 00:00 [pubmed] PHST- 1983/03/01 00:01 [medline] PHST- 1983/03/01 00:00 [entrez] AID - 0021-9150(83)90177-6 [pii] PST - ppublish SO - Atherosclerosis. 1983 Mar;46(3):269-73. PMID- 6844377 OWN - NLM STAT- MEDLINE DCOM- 19830610 LR - 20131121 IS - 0031-6989 (Print) IS - 0031-6989 (Linking) VI - 15 IP - 2 DP - 1983 Feb TI - Experimental studies on the hypolipidemic activity of chloridarol. PG - 201-15 AB - The efficacy of chloridarol (2-benzofuryl-p-chlorophenyl carbinol) as hypolipidemic agent was evaluated in rats and rabbits. In normolipidemic rats chloridarol, at doses ranging from 50 to 200 mg/kg/day, decreased plasma triglycerides without affecting cholesterolemia and fast- or norepinephrine-induced lipolysis. The drug proved effective in reducing fructose-induced hypertriglyceridemia and dietary hypercholesterolemia in rats; in the latter model chloridarol significantly raised both the HDL cholesterol and the HDL/VLDL + LDL cholesterol ratio. In hyperlipidemic rabbits the drug had no effect on plasma cholesterol, but it lowered triglyceridemia. The action of chloridarol on rat liver ultrastructure was also investigated. Treatment for one month induced peroxisome proliferation, less marked, however, than that elicited by clofibrate; after a prolonged chloridarol treatment (9 months), this effect had almost completely disappeared and the ultrastructure of the hepatocytes was close to that of controls. FAU - Bernini, F AU - Bernini F FAU - Musanti, R AU - Musanti R FAU - Trezzi, E AU - Trezzi E FAU - Corsini, A AU - Corsini A FAU - Fumagalli, R AU - Fumagalli R FAU - Meldolesi, J AU - Meldolesi J FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Pharmacol Res Commun JT - Pharmacological research communications JID - 0236354 RN - 0 (Benzofurans) RN - 0 (Fatty Acids, Nonesterified) RN - 0 (Hypolipidemic Agents) RN - 0 (Nicotinic Acids) RN - 2L2063955H (cloridarol) RN - HPN91K7FU3 (Clofibrate) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Benzofurans/*pharmacology MH - Clofibrate/pharmacology MH - Diet MH - Fatty Acids, Nonesterified/blood MH - *Hypolipidemic Agents MH - Lipolysis/drug effects MH - Liver/ultrastructure MH - Male MH - Nicotinic Acids/pharmacology MH - Norepinephrine/pharmacology MH - Rats MH - Rats, Inbred Strains EDAT- 1983/02/01 00:00 MHDA- 1983/02/01 00:01 CRDT- 1983/02/01 00:00 PHST- 1983/02/01 00:00 [pubmed] PHST- 1983/02/01 00:01 [medline] PHST- 1983/02/01 00:00 [entrez] PST - ppublish SO - Pharmacol Res Commun. 1983 Feb;15(2):201-15. PMID- 6624548 OWN - NLM STAT- MEDLINE DCOM- 19831123 LR - 20161123 IS - 0001-6101 (Print) IS - 0001-6101 (Linking) VI - 214 IP - 2 DP - 1983 TI - A new case of familial LCAT deficiency. PG - 173-6 AB - Twenty-eight patients with familial lecithin:cholesterol acyltransferase deficiency have been reported to date. We report a new Italian case who presents the clinical and biochemical characteristics of the disease. Typical disc-shaped high density lipoproteins (d = 1.063-1.21 g/ml) were detected by electron microscopy. An abnormal distribution of apolipoproteins in the different lipoprotein fractions was found by sodium dodecyl sulphate polyacrylamide electrophoresis. FAU - Vergani, C AU - Vergani C FAU - Catapano, A L AU - Catapano AL FAU - Roma, P AU - Roma P FAU - Giudici, G AU - Giudici G LA - eng PT - Case Reports PT - Journal Article PL - Sweden TA - Acta Med Scand JT - Acta medica Scandinavica JID - 0370330 RN - 0 (Apolipoproteins) RN - 0 (Lipoproteins, HDL) SB - IM MH - Adolescent MH - Apolipoproteins/blood MH - Electrophoresis, Polyacrylamide Gel MH - Humans MH - Hypolipoproteinemias/*genetics MH - Lecithin Cholesterol Acyltransferase Deficiency/blood/*genetics MH - Lipoproteins, HDL/blood MH - Male MH - Microscopy, Electron EDAT- 1983/01/01 00:00 MHDA- 1983/01/01 00:01 CRDT- 1983/01/01 00:00 PHST- 1983/01/01 00:00 [pubmed] PHST- 1983/01/01 00:01 [medline] PHST- 1983/01/01 00:00 [entrez] PST - ppublish SO - Acta Med Scand. 1983;214(2):173-6. PMID- 7089427 OWN - NLM STAT- MEDLINE DCOM- 19820807 LR - 20131121 IS - 0390-5748 (Print) IS - 0390-5748 (Linking) VI - 12 IP - 1 DP - 1982 Jan-Mar TI - Formation of high density lipoprotein-like particles from chylomicrons. PG - 51-62 FAU - Capurso, A AU - Capurso A FAU - Catapano, A L AU - Catapano AL FAU - Mills, G L AU - Mills GL FAU - Mazzarella, L AU - Mazzarella L FAU - Pace, L AU - Pace L FAU - Martorano, M AU - Martorano M FAU - D'Agostino, C AU - D'Agostino C FAU - Resta, F AU - Resta F FAU - Mogavero, A M AU - Mogavero AM FAU - Colotta, F AU - Colotta F FAU - Bonomo, L AU - Bonomo L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Italy TA - Ric Clin Lab JT - La Ricerca in clinica e in laboratorio JID - 7613947 RN - 0 (Apolipoproteins) RN - 0 (Chylomicrons) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, HDL) RN - 0 (Phospholipids) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Adult MH - Apolipoproteins/metabolism MH - Cholesterol/metabolism MH - Chylomicrons/*blood MH - Humans MH - Hyperlipoproteinemia Type V/blood/*genetics MH - Immunoelectrophoresis, Two-Dimensional MH - Lipolysis MH - Lipoprotein Lipase/metabolism MH - Lipoproteins/metabolism MH - Lipoproteins, HDL/*metabolism MH - Male MH - Microscopy, Electron MH - Middle Aged MH - Phospholipids/metabolism EDAT- 1982/01/01 00:00 MHDA- 1982/01/01 00:01 CRDT- 1982/01/01 00:00 PHST- 1982/01/01 00:00 [pubmed] PHST- 1982/01/01 00:01 [medline] PHST- 1982/01/01 00:00 [entrez] PST - ppublish SO - Ric Clin Lab. 1982 Jan-Mar;12(1):51-62. PMID- 7046021 OWN - NLM STAT- MEDLINE DCOM- 19820807 LR - 20061115 IS - 0390-5748 (Print) IS - 0390-5748 (Linking) VI - 12 IP - 1 DP - 1982 Jan-Mar TI - Apolipoprotein C-II and lipoprotein lipase activity. PG - 35-40 FAU - Catapano, A L AU - Catapano AL LA - eng PT - Comparative Study PT - Journal Article PT - Review PL - Italy TA - Ric Clin Lab JT - La Ricerca in clinica e in laboratorio JID - 7613947 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins C) RN - 0 (Chylomicrons) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Peptide Fragments) RN - 0 (Phospholipids) RN - 0 (Triglycerides) RN - 9005-49-6 (Heparin) RN - EC 3.1.1.3 (Lipase) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Adipose Tissue/enzymology MH - Animals MH - Apolipoprotein C-II MH - Apolipoproteins/*metabolism/pharmacology MH - *Apolipoproteins C MH - Chylomicrons/metabolism MH - Endothelium/enzymology MH - Enzyme Activation/drug effects MH - Heparin/metabolism MH - Humans MH - Lipase/metabolism MH - Lipoprotein Lipase/*metabolism MH - Lipoproteins, HDL/metabolism MH - Lipoproteins, VLDL/metabolism MH - Liver/metabolism MH - Muscles/enzymology MH - Myocardium/enzymology MH - Peptide Fragments/pharmacology MH - Phospholipids/metabolism MH - Structure-Activity Relationship MH - Substrate Specificity MH - Triglycerides/metabolism RF - 29 EDAT- 1982/01/01 00:00 MHDA- 1982/01/01 00:01 CRDT- 1982/01/01 00:00 PHST- 1982/01/01 00:00 [pubmed] PHST- 1982/01/01 00:01 [medline] PHST- 1982/01/01 00:00 [entrez] PST - ppublish SO - Ric Clin Lab. 1982 Jan-Mar;12(1):35-40. PMID- 7332603 OWN - NLM STAT- MEDLINE DCOM- 19820420 LR - 20141120 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 40 IP - 3-4 DP - 1981 Nov-Dec TI - Pharmacological studies on tiadenol in type IV patients. Evidence for a mechanism of action different from other lipid-lowering drugs. PG - 245-55 AB - Tiadenol [bis(hydroxyethylthio) 1-10 decane], a new absorbable hypolipidemic agent differing in chemical structure from clofibrate and related compounds, was tested in hypertriglyceridemic patients, both responsive and nonresponsive to dietary treatment. Tiadenol administration was remarkably effective in inhibiting fructose induced hypertriglyceridemia in diet responsive type IV patients; it was ineffective in patients with stable, diet refractory, hypertriglyceridemia. The significant reduction of plasma triglycerides (-42%) in sensitive patients, was not accompanied in this study, by the activation of plasma lipoprotein and hepatic lipases. In a second, longer term investigation of stable type IV patients, tiadenol administration resulted in significant triglyceride decreases in the very low density lipoproteins (VLDL) (-45%), as well as in the low and high density lipoproteins (LDL and HDL) (both -25%). The cholesterol content of LDL and HDL was not modified. In VLDL a significant reduction of apoprotein E was observed (from 15.2 +/- 4.9 to 11.9 +/- 5.9% of VLDL proteins). The reported observations are consistent with a difference in the mode of action of tiadenol from that of other lipid lowering agents, particularly of the clofibrate type. FAU - Franceschini, G AU - Franceschini G FAU - Poli, A AU - Poli A FAU - Catapano, A L AU - Catapano AL FAU - Gatti, E AU - Gatti E FAU - Sirtori, M AU - Sirtori M FAU - Gianfranceschi, G AU - Gianfranceschi G FAU - Sirtori, C R AU - Sirtori CR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apoproteins) RN - 0 (Fatty Alcohols) RN - 0 (Hypolipidemic Agents) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, VLDL) RN - 22251270CX (tiadenol) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.1.3 (Lipase) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Apoproteins/analysis MH - Cholesterol/blood MH - Fatty Alcohols/*pharmacology/therapeutic use MH - Humans MH - Hyperlipoproteinemia Type IV/blood/*drug therapy MH - Hypolipidemic Agents/*pharmacology MH - Lipase/blood MH - Lipoprotein Lipase/blood MH - Lipoproteins/blood MH - Lipoproteins, VLDL/analysis EDAT- 1981/11/01 00:00 MHDA- 1981/11/01 00:01 CRDT- 1981/11/01 00:00 PHST- 1981/11/01 00:00 [pubmed] PHST- 1981/11/01 00:01 [medline] PHST- 1981/11/01 00:00 [entrez] AID - 0021-9150(81)90134-9 [pii] PST - ppublish SO - Atherosclerosis. 1981 Nov-Dec;40(3-4):245-55. PMID- 7455910 OWN - NLM STAT- MEDLINE DCOM- 19810324 LR - 20131121 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 89 IP - 2 DP - 1981 Feb TI - Reduced apoprotein B and increased lipoprotein turnover in cholesterol-fed rabbits after partial ileal bypass. PG - 243-51 AB - Plasma lipid and lipoprotein levels and composition of the very low-, low-, and high-density lipoproteins (VLDL, LDL, HDL) were studied in white New Zealand rabbits in the control state, 8 weeks after initiation of a 2% cholesterol-enriched diet, and sequentially for 16 weeks following a partial ileal bypass (PIB) procedure. Turnover and aortic uptake of 125I-labeled VLDL, obtained from the rabbits before and 16 weeks after PIB, were also analyzed. A significant reduction of plasma cholesterol from the postdiet levels to well below the prediet mean, despite continuation of the high cholesterol diet, followed PIB. A very early reduction of the apoprotein B percentage content in both VLDL and LDL was observed after the procedure, even when a relative cholesterol ester enrichment of these lipoproteins was still present. HDL cholesterol levels were somewhat lowered by the experimental diet and further reduced after PIB. 125I-labeled VLDL after PIB showed a reduced arterial uptake, as compared to the same lipoproteins from animals before PIB. These findings may provide an interpretation for the decreased atherogenesis after PIB. FAU - Sirtori, C R AU - Sirtori CR FAU - Ghiselli, G C AU - Ghiselli GC FAU - Catapano, A L AU - Catapano AL FAU - Lovati, M R AU - Lovati MR FAU - Fragiacomo, C AU - Fragiacomo C FAU - Fox, U AU - Fox U FAU - Majone, G AU - Majone G FAU - Buchwald, H AU - Buchwald H LA - eng PT - Journal Article PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (Apoproteins) RN - 0 (Cholesterol, Dietary) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) SB - AIM SB - IM MH - Animals MH - Apoproteins/*blood MH - Chemical Fractionation MH - Cholesterol/blood MH - Cholesterol, Dietary/*metabolism MH - Diet, Atherogenic MH - Electrophoresis, Polyacrylamide Gel MH - Ileum/*surgery MH - Lipoproteins/*metabolism MH - Lipoproteins, HDL/blood MH - Lipoproteins, LDL/blood MH - Lipoproteins, VLDL/blood MH - Male MH - Rabbits MH - Triglycerides/blood EDAT- 1981/02/01 00:00 MHDA- 1981/02/01 00:01 CRDT- 1981/02/01 00:00 PHST- 1981/02/01 00:00 [pubmed] PHST- 1981/02/01 00:01 [medline] PHST- 1981/02/01 00:00 [entrez] PST - ppublish SO - Surgery. 1981 Feb;89(2):243-51. PMID- 7295047 OWN - NLM STAT- MEDLINE DCOM- 19811222 LR - 20141120 IS - 0098-6127 (Print) IS - 0098-6127 (Linking) VI - 9 IP - 2 DP - 1981 TI - In vitro catabolism of human very low density lipoproteins: fate of apoproteins B and C. PG - 87-95 AB - The fate of apo C-II, apo C-III and apo B during the in vitro catabolism of human very low density lipoproteins (VLDL) by the action of purified lipoprotein lipase was studied. Up to 58 percent of triglyceride apo C-II and C-III was released from VLDL during hydrolysis and at a similar rate. The amount of C apoproteins lost was proportional to triglyceride hydrolysis. The apo B content of VLDL remained constant. From these studies we conclude that during the hydrolysis of human VLDL, lipoprotein lipase, while including a net loss of apo C, is not responsible for major changes in the apo C-II/C-III ratio. FAU - Catapano, A L AU - Catapano AL FAU - Capurso, A AU - Capurso A FAU - Kinnunen, P K AU - Kinnunen PK LA - eng PT - Journal Article PL - United States TA - Artery JT - Artery JID - 7508494 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoprotein C-III) RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins B) RN - 0 (Apolipoproteins C) RN - 0 (Lipoproteins, VLDL) RN - 0 (Triglycerides) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Apolipoprotein C-II MH - Apolipoprotein C-III MH - Apolipoproteins/*metabolism MH - Apolipoproteins B MH - Apolipoproteins C MH - Humans MH - In Vitro Techniques MH - Lipoprotein Lipase/*metabolism MH - Lipoproteins, VLDL/*metabolism MH - Triglycerides/metabolism EDAT- 1981/01/01 00:00 MHDA- 1981/01/01 00:01 CRDT- 1981/01/01 00:00 PHST- 1981/01/01 00:00 [pubmed] PHST- 1981/01/01 00:01 [medline] PHST- 1981/01/01 00:00 [entrez] PST - ppublish SO - Artery. 1981;9(2):87-95. PMID- 7401943 OWN - NLM STAT- MEDLINE DCOM- 19801021 LR - 20181113 IS - 0024-4201 (Print) IS - 0024-4201 (Linking) VI - 15 IP - 6 DP - 1980 Jun TI - Abnormal suppression of 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured human fibroblasts by hypertriglyceridemic very low density lipoprotein subclasses. PG - 456-63 FAU - Gianturco, S H AU - Gianturco SH FAU - Packard, C J AU - Packard CJ FAU - Shepherd, J AU - Shepherd J FAU - Smith, L C AU - Smith LC FAU - Catapano, A L AU - Catapano AL FAU - Sybers, H D AU - Sybers HD FAU - Gotto, A M Jr AU - Gotto AM Jr LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Lipids JT - Lipids JID - 0060450 RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Triglycerides) RN - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases) SB - IM MH - Adult MH - Cells, Cultured MH - Fibroblasts/*enzymology MH - Humans MH - Hydroxymethylglutaryl CoA Reductases/*blood MH - Hyperlipidemias/*blood MH - Infant, Newborn MH - Kinetics MH - Lipoproteins, LDL/blood/pharmacology MH - Lipoproteins, VLDL/blood/*pharmacology MH - Male MH - Triglycerides/*blood EDAT- 1980/06/01 00:00 MHDA- 2001/03/28 10:01 CRDT- 1980/06/01 00:00 PHST- 1980/06/01 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1980/06/01 00:00 [entrez] PST - ppublish SO - Lipids. 1980 Jun;15(6):456-63. PMID- 7378122 OWN - NLM STAT- MEDLINE DCOM- 19800712 LR - 20061115 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 35 IP - 4 DP - 1980 Apr TI - The distribution of apo C-II and apo C-III in very low density lipoproteins of normal and type IV subjects. PG - 419-24 AB - The apoC-II/apoC-III ratio and the distribution of C apoproteins as percentage of the total protein in VLDL obtained from normolipidemic and type IV patients was studied by analytical isoelectrofocusing. While the percentage concentration of apoCI-III was unchanged that of apoC-II was 9.2% of total protein in normal VLDL and only 7.4% in type IV VLDL (P less than 0.05). The apoC-II/apo C-III ratio significantly decreased in type IV patients. The analysis of VLDL subfractions obtained by density gradient ultracentrifugation gave essentially the same results. These data confirm the decrease of apoC-II as % of the protein in type IV VLDL and suggest that the decrease of the apoC-II/apoC-iii ratio in type IV patients is related only to the decreased content of apoC-II. Whether the reduced apoC-II percentage amount or the decreased apoC-II/apo C-III ratio are related to the hypertriglyceridemia in type IV subjects is still unclear. FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoprotein C-III) RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins C) RN - 0 (Lipoproteins, VLDL) SB - IM MH - Apolipoprotein C-II MH - Apolipoprotein C-III MH - Apolipoproteins/*analysis MH - *Apolipoproteins C MH - Humans MH - Hyperlipoproteinemia Type IV/*blood MH - Isoelectric Focusing MH - Lipoproteins, VLDL/*analysis MH - Male EDAT- 1980/04/01 00:00 MHDA- 1980/04/01 00:01 CRDT- 1980/04/01 00:00 PHST- 1980/04/01 00:00 [pubmed] PHST- 1980/04/01 00:01 [medline] PHST- 1980/04/01 00:00 [entrez] AID - 0021-9150(80)90182-3 [pii] PST - ppublish SO - Atherosclerosis. 1980 Apr;35(4):419-24. PMID- 6930927 OWN - NLM STAT- MEDLINE DCOM- 19800926 LR - 20061115 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 348 DP - 1980 TI - Activation of lipoprotein lipase by synthetic fragments of apolipoprotein C-II. PG - 213-23 FAU - Smith, L C AU - Smith LC FAU - Voyta, J C AU - Voyta JC FAU - Catapano, A L AU - Catapano AL FAU - Kinnunen, P K AU - Kinnunen PK FAU - Gotto, A M Jr AU - Gotto AM Jr FAU - Sparrow, J T AU - Sparrow JT LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Apolipoprotein C-II) RN - 0 (Apolipoproteins) RN - 0 (Apolipoproteins C) RN - 0 (Peptide Fragments) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Amino Acid Sequence MH - Apolipoprotein C-II MH - Apolipoproteins/*metabolism MH - *Apolipoproteins C MH - Enzyme Activation/drug effects MH - Lipoprotein Lipase/*metabolism MH - Models, Molecular MH - Peptide Fragments/pharmacology MH - Protein Binding MH - Structure-Activity Relationship EDAT- 1980/01/01 00:00 MHDA- 2001/03/28 10:01 CRDT- 1980/01/01 00:00 PHST- 1980/01/01 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1980/01/01 00:00 [entrez] PST - ppublish SO - Ann N Y Acad Sci. 1980;348:213-23. PMID- 226096 OWN - NLM STAT- MEDLINE DCOM- 19791121 LR - 20061115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 89 IP - 3 DP - 1979 Aug 13 TI - Lipolysis of ApoC-II deficient very low density lipoproteins: enhancement of lipoprotein lipase action by synthetic fragments of apoC-II. PG - 951-7 FAU - Catapano, A L AU - Catapano AL FAU - Kinnunen, P K AU - Kinnunen PK FAU - Breckenridge, W C AU - Breckenridge WC FAU - Gotto, A M Jr AU - Gotto AM Jr FAU - Jackson, R L AU - Jackson RL FAU - Little, J A AU - Little JA FAU - Smith, L C AU - Smith LC FAU - Sparrow, J T AU - Sparrow JT LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Apolipoproteins) RN - 0 (Lipoproteins, VLDL) RN - 0 (Peptide Fragments) RN - 0 (Triglycerides) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Animals MH - Apolipoproteins/*deficiency MH - Cattle MH - Humans MH - Kinetics MH - Lipid Mobilization MH - Lipoprotein Lipase/*metabolism MH - Lipoproteins, VLDL/*pharmacology MH - Male MH - Middle Aged MH - Milk/enzymology MH - Peptide Fragments/pharmacology MH - Triglycerides EDAT- 1979/08/13 00:00 MHDA- 2001/03/28 10:01 CRDT- 1979/08/13 00:00 PHST- 1979/08/13 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1979/08/13 00:00 [entrez] AID - 0006-291X(79)91870-9 [pii] PST - ppublish SO - Biochem Biophys Res Commun. 1979 Aug 13;89(3):951-7. PMID- 388469 OWN - NLM STAT- MEDLINE DCOM- 19800128 LR - 20031114 IS - 0031-6989 (Print) IS - 0031-6989 (Linking) VI - 11 IP - 7 DP - 1979 Jul TI - Glycosaminoglycans and lipoprotein metabolism: an overview. PG - 571-83 FAU - Ghiselli, G C AU - Ghiselli GC FAU - Catapano, A L AU - Catapano AL LA - eng PT - Journal Article PT - Review PL - United States TA - Pharmacol Res Commun JT - Pharmacological research communications JID - 0236354 RN - 0 (Apoproteins) RN - 0 (Glycosaminoglycans) RN - 0 (Lipoproteins) RN - 9005-49-6 (Heparin) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Animals MH - Apoproteins/metabolism MH - Glycosaminoglycans/*pharmacology MH - Heparin/pharmacology MH - Lipoprotein Lipase/metabolism MH - Lipoproteins/blood/*metabolism MH - Liver/metabolism RF - 45 EDAT- 1979/07/01 00:00 MHDA- 1979/07/01 00:01 CRDT- 1979/07/01 00:00 PHST- 1979/07/01 00:00 [pubmed] PHST- 1979/07/01 00:01 [medline] PHST- 1979/07/01 00:00 [entrez] PST - ppublish SO - Pharmacol Res Commun. 1979 Jul;11(7):571-83. PMID- 216685 OWN - NLM STAT- MEDLINE DCOM- 19790426 LR - 20061115 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 254 IP - 4 DP - 1979 Feb 25 TI - Suppression of 3-hydroxy-3-methylglutaryl-CoA reductase by low density lipoproteins produced in vitro by lipoprotein lipase action on nonsuppressive very low density lipoproteins. PG - 1007-9 AB - Very low density lipoproteins (VLDL), Sf60 to 400, from normolipemic individuals do not suppress 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured normal human fibroblasts at concentrations 20-fold higher than those of low density lipoproteins (LDL) that give total suppression. To determine if these VLDL contain all of the structural elements necessary for receptor-mediated suppression, they were converted in vitro with bovine milk lipoprotein lipase to low density lipoproteins. These LDL-like lipoproteins were as effective in suppression as LDL isolated directly from plasma, with half-maximal and complete suppression at 1 and 4 microgram of cholesterol ml-1. Neither native LDL nor LDL produced in vitro suppressed receptor-negative fibroblasts. We conclude that action of lipoprotein lipase on VLDL leads to a rearrangement of lipoprotein components that permits interaction of LDL produced in vitro with the LDL-specific cell surface receptor of fibroblasts and subsequent suppression of 3-hydroxy-3-methylglutaryl-CoA reductase. FAU - Catapano, A L AU - Catapano AL FAU - Gianturco, S H AU - Gianturco SH FAU - Kinnunen, P K AU - Kinnunen PK FAU - Eisenberg, S AU - Eisenberg S FAU - Gotto, A M Jr AU - Gotto AM Jr FAU - Smith, L C AU - Smith LC LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - EC 3.1.1.34 (Lipoprotein Lipase) SB - IM MH - Cells, Cultured MH - Fibroblasts/enzymology MH - Humans MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors MH - Hypercholesterolemia/enzymology MH - Kinetics MH - Lipoprotein Lipase/*metabolism MH - Lipoproteins, LDL/*pharmacology MH - *Lipoproteins, VLDL MH - Male MH - Molecular Weight MH - Skin/enzymology EDAT- 1979/02/25 00:00 MHDA- 2001/03/28 10:01 CRDT- 1979/02/25 00:00 PHST- 1979/02/25 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1979/02/25 00:00 [entrez] PST - ppublish SO - J Biol Chem. 1979 Feb 25;254(4):1007-9. PMID- 32216 OWN - NLM STAT- MEDLINE DCOM- 19790313 LR - 20061115 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 19 IP - 8 DP - 1978 Nov TI - Quantification of apoC-II and apoC-III of human very low density lipoproteins by analytical isoelectric focusing. PG - 1047-52 AB - ApoC-II and apoC-III of human very low density lipoproteins (VLDL) have been quantified by analytical isoelectric focusing (IEF) between pH 4 and 6 in polyacrylamide gels containing 8 M urea. The isoelectric point of apoC-III0 is pH 4.93; apoC-II, pH 4.78; apoC-III1, pH 4.72, and apoC-III2, pH 4.54. ApoC-I is not found in the pH range between pH 4 and 6. Two minor peptides, apoC-IV and apoC-V, with isoelectric points of pH 4.61 and 4.44, respectively, are apoproteins not previously identified. The sensitivity (5--40 microgram) and reproducibility (+/- 8%) of this method allow quantitative analysis of apoC-II and apoC-III distribution in VLDL. FAU - Catapano, A L AU - Catapano AL FAU - Jackson, R L AU - Jackson RL FAU - Gilliam, E B AU - Gilliam EB FAU - Gotto, A M Jr AU - Gotto AM Jr FAU - Smith, L C AU - Smith LC LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Apolipoproteins) RN - 0 (Lipoproteins, VLDL) RN - EC 3.2.1.18 (Neuraminidase) SB - IM MH - Apolipoproteins/blood MH - Humans MH - Hydrogen-Ion Concentration MH - Isoelectric Focusing/methods MH - Lipoproteins, VLDL/*blood MH - Neuraminidase EDAT- 1978/11/01 00:00 MHDA- 2001/03/28 10:01 CRDT- 1978/11/01 00:00 PHST- 1978/11/01 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1978/11/01 00:00 [entrez] PST - ppublish SO - J Lipid Res. 1978 Nov;19(8):1047-52.