PMID- 30665623 OWN - NLM STAT- MEDLINE DCOM- 20190313 LR - 20190313 IS - 1873-3735 (Electronic) IS - 0165-6147 (Linking) VI - 40 IP - 2 DP - 2019 Feb TI - Lysosomal Acid Lipase: From Cellular Lipid Handler to Immunometabolic Target. PG - 104-115 LID - S0165-6147(18)30231-1 [pii] LID - 10.1016/j.tips.2018.12.006 [doi] AB - Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CEs) and triglycerides (TGs) to free cholesterol (FC) and free fatty acids (FFAs), which are then used for metabolic purposes in the cell. The process also occurs in immune cells that adapt their metabolic machinery to cope with the different energetic requirements associated with cell activation, proliferation, and polarization. LAL deficiency (LALD) causes severe lipid accumulation and affects the immunometabolic signature in animal models. In humans, LAL deficiency is associated with a peculiar clinical immune phenotype, secondary hemophagocytic lymphohistiocytosis. These observations suggest that LAL might play an important role in cellular immunometabolic modulation, and availability of an effective enzyme replacement strategy makes LAL an attractive target to rewire the metabolic machinery of immune cells beyond its role in controlling cellular lipid metabolism. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Gomaraschi, M AU - Gomaraschi M AD - Center E. Grossi Paoletti, Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan 20133, Italy. FAU - Bonacina, F AU - Bonacina F AD - Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan 20133, Italy. FAU - Norata, G D AU - Norata GD AD - Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Universita Degli Studi di Milano, Milan 20133, Italy; SISA Centre, Bassini Hospital, Cinisello Balsamo, 20092, Italy. Electronic address: Danilo.Norata@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190118 PL - England TA - Trends Pharmacol Sci JT - Trends in pharmacological sciences JID - 7906158 RN - EC 3.1.1.13 (Sterol Esterase) RN - Lysosomal acid lipase deficiency SB - IM MH - Animals MH - Humans MH - Immune System/*enzymology/metabolism MH - Lipid Metabolism MH - Liver/immunology/metabolism MH - Sterol Esterase/*immunology/*metabolism MH - Wolman Disease/immunology/metabolism OTO - NOTNLM OT - *cholesterol OT - *enzyme replacement therapy OT - *fatty acids OT - *immune response OT - *lysosomal acid lipase EDAT- 2019/01/23 06:00 MHDA- 2019/03/14 06:00 CRDT- 2019/01/23 06:00 PHST- 2018/09/17 00:00 [received] PHST- 2018/12/05 00:00 [revised] PHST- 2018/12/06 00:00 [accepted] PHST- 2019/01/23 06:00 [pubmed] PHST- 2019/03/14 06:00 [medline] PHST- 2019/01/23 06:00 [entrez] AID - S0165-6147(18)30231-1 [pii] AID - 10.1016/j.tips.2018.12.006 [doi] PST - ppublish SO - Trends Pharmacol Sci. 2019 Feb;40(2):104-115. doi: 10.1016/j.tips.2018.12.006. Epub 2019 Jan 18. PMID- 30340893 OWN - NLM STAT- In-Data-Review LR - 20190106 IS - 1097-6795 (Electronic) IS - 0894-7317 (Linking) VI - 32 IP - 1 DP - 2019 Jan TI - Impact of Cardiovascular Risk Factors and Pharmacologic Treatments on Carotid Intraplaque Neovascularization Detected by Contrast-Enhanced Ultrasound. PG - 113-120.e6 LID - S0894-7317(18)30499-1 [pii] LID - 10.1016/j.echo.2018.09.001 [doi] AB - BACKGROUND: Neovascularization is a marker of plaque vulnerability that can be assessed noninvasively using contrast-enhanced ultrasound (CEUS). The presence and extent of plaque neovascularization and their relation to cardiovascular risk factors and treatments were assessed in asymptomatic patients with carotid stenosis of intermediate severity and no indication for revascularization. METHODS: Sixty-six patients aged 69 +/- 8 years (59% men) were prospectively enrolled. Plaque neovascularization was assessed using CEUS with sulfur hexafluoride contrast in each of the four carotid segments bilaterally (a total of 528 segments). In each plaque, the presence or absence of contrast enhancement was assessed semiquantitatively as CEUS grade 1 (no signal or signal confined to the adventitia and/or shoulder of the plaque) or CEUS grade 2 (signal within the plaque). RESULTS: Plaques were detectable in 289 of 528 carotid segments (54.7%). CEUS grade 2 was present in at least one plaque in 48 of 66 patients (72.7%) and was not influenced by stenosis severity or morphology. The highest CEUS grade 2 prevalence was observed in patients with diabetes and the lowest in those treated with angiotensin-converting enzyme inhibitors and statins, especially when low-density lipoprotein cholesterol was <100 mg/dL. Patients with multiple CEUS grade 2 plaques (20 of 66 [30%]) had both higher low-density lipoprotein and higher C-reactive protein. CONCLUSION: Intraplaque neovascularization is frequent in asymptomatic patients with intermediate carotid stenosis and is more prevalent in those with diabetes. Low-density lipoprotein cholesterol < 100 mg/dL and treatment with angiotensin-converting enzyme inhibitors seem to confer protection from neovascularization, although larger interventional studies are necessary to confirm these data. CI - Copyright (c) 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved. FAU - Magnoni, Marco AU - Magnoni M AD - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: magnoni.marco@hsr.it. FAU - Ammirati, Enrico AU - Ammirati E AD - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; De Gasperis Cardio Center, Niguarda Hospital, Milan, Italy. FAU - Moroni, Francesco AU - Moroni F AD - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Camici, Paolo G AU - Camici PG AD - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy. LA - eng PT - Journal Article DEP - 20181016 PL - United States TA - J Am Soc Echocardiogr JT - Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography JID - 8801388 OTO - NOTNLM OT - Carotid atherosclerosis OT - Contrast-enhanced ultrasound OT - Plaque neovascularization OT - Risk factor OT - Vasa vasorum EDAT- 2018/10/21 06:00 MHDA- 2018/10/21 06:00 CRDT- 2018/10/21 06:00 PHST- 2017/11/10 00:00 [received] PHST- 2018/10/21 06:00 [pubmed] PHST- 2018/10/21 06:00 [medline] PHST- 2018/10/21 06:00 [entrez] AID - S0894-7317(18)30499-1 [pii] AID - 10.1016/j.echo.2018.09.001 [doi] PST - ppublish SO - J Am Soc Echocardiogr. 2019 Jan;32(1):113-120.e6. doi: 10.1016/j.echo.2018.09.001. Epub 2018 Oct 16. PMID- 30478348 OWN - NLM STAT- In-Data-Review LR - 20181204 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Nov 27 TI - Author Correction: Cluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans. PG - 17472 LID - 10.1038/s41598-018-35958-4 [doi] AB - A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. FAU - Galli, Alessandra AU - Galli A AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Maffioli, Elisa AU - Maffioli E AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Sogne, Elisa AU - Sogne E AUID- ORCID: http://orcid.org/0000-0003-2097-4358 AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. AD - Biological and Environmental Science and Engineering Division, KAUST, Jeddah, Saudi Arabia. FAU - Moretti, Stefania AU - Moretti S AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Di Cairano, Eliana Sara AU - Di Cairano ES AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Negri, Armando AU - Negri A AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Nonnis, Simona AU - Nonnis S AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Borghi, Francesca AU - Borghi F AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Podesta, Alessandro AU - Podesta A AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Bertuzzi, Federico AU - Bertuzzi F AD - Niguarda Hospital, Milan, Italy. FAU - Milani, Paolo AU - Milani P AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Lenardi, Cristina AU - Lenardi C AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Tedeschi, Gabriella AU - Tedeschi G AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Perego, Carla AU - Perego C AUID- ORCID: http://orcid.org/0000-0003-3027-1779 AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. carla.perego@unimi.it. LA - eng PT - Published Erratum DEP - 20181127 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 EFR - Sci Rep. 2018 Jul 2;8(1):9979. PMID: 29967323 PMC - PMC6255846 EDAT- 2018/11/28 06:00 MHDA- 2018/11/28 06:00 CRDT- 2018/11/28 06:00 PHST- 2018/11/28 06:00 [entrez] PHST- 2018/11/28 06:00 [pubmed] PHST- 2018/11/28 06:00 [medline] AID - 10.1038/s41598-018-35958-4 [doi] AID - 10.1038/s41598-018-35958-4 [pii] PST - epublish SO - Sci Rep. 2018 Nov 27;8(1):17472. doi: 10.1038/s41598-018-35958-4. PMID- 30235339 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20190225 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 9 DP - 2018 TI - Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration. PG - e0204633 LID - 10.1371/journal.pone.0204633 [doi] AB - [This corrects the article DOI: 10.1371/journal.pone.0191172.]. FAU - Lorenz, Matthias W AU - Lorenz MW FAU - Gao, Lu AU - Gao L FAU - Ziegelbauer, Kathrin AU - Ziegelbauer K FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Empana, Jean Philippe AU - Empana JP FAU - Schmidtmann, Irene AU - Schmidtmann I FAU - Lin, Hung-Ju AU - Lin HJ FAU - McLachlan, Stela AU - McLachlan S FAU - Bokemark, Lena AU - Bokemark L FAU - Ronkainen, Kimmo AU - Ronkainen K FAU - Amato, Mauro AU - Amato M FAU - Schminke, Ulf AU - Schminke U FAU - Srinivasan, Sathanur R AU - Srinivasan SR FAU - Lind, Lars AU - Lind L FAU - Okazaki, Shuhei AU - Okazaki S FAU - Stehouwer, Coen D A AU - Stehouwer CDA FAU - Willeit, Peter AU - Willeit P FAU - Polak, Joseph F AU - Polak JF FAU - Steinmetz, Helmuth AU - Steinmetz H FAU - Sander, Dirk AU - Sander D FAU - Poppert, Holger AU - Poppert H FAU - Desvarieux, Moise AU - Desvarieux M FAU - Ikram, M Arfan AU - Ikram MA FAU - Johnsen, Stein Harald AU - Johnsen SH FAU - Staub, Daniel AU - Staub D FAU - Sirtori, Cesare R AU - Sirtori CR FAU - Iglseder, Bernhard AU - Iglseder B FAU - Beloqui, Oscar AU - Beloqui O FAU - Engstrom, Gunnar AU - Engstrom G FAU - Friera, Alfonso AU - Friera A FAU - Rozza, Francesco AU - Rozza F FAU - Xie, Wuxiang AU - Xie W FAU - Parraga, Grace AU - Parraga G FAU - Grigore, Liliana AU - Grigore L FAU - Plichart, Matthieu AU - Plichart M FAU - Blankenberg, Stefan AU - Blankenberg S FAU - Su, Ta-Chen AU - Su TC FAU - Schmidt, Caroline AU - Schmidt C FAU - Tuomainen, Tomi-Pekka AU - Tuomainen TP FAU - Veglia, Fabrizio AU - Veglia F FAU - Volzke, Henry AU - Volzke H FAU - Nijpels, Giel AU - Nijpels G FAU - Willeit, Johann AU - Willeit J FAU - Sacco, Ralph L AU - Sacco RL FAU - Franco, Oscar H AU - Franco OH FAU - Uthoff, Heiko AU - Uthoff H FAU - Hedblad, Bo AU - Hedblad B FAU - Suarez, Carmen AU - Suarez C FAU - Izzo, Raffaele AU - Izzo R FAU - Zhao, Dong AU - Zhao D FAU - Wannarong, Thapat AU - Wannarong T FAU - Catapano, Alberico AU - Catapano A FAU - Ducimetiere, Pierre AU - Ducimetiere P FAU - Espinola-Klein, Christine AU - Espinola-Klein C FAU - Chien, Kuo-Liong AU - Chien KL FAU - Price, Jackie F AU - Price JF FAU - Bergstrom, Goran AU - Bergstrom G FAU - Kauhanen, Jussi AU - Kauhanen J FAU - Tremoli, Elena AU - Tremoli E FAU - Dorr, Marcus AU - Dorr M FAU - Berenson, Gerald AU - Berenson G FAU - Kitagawa, Kazuo AU - Kitagawa K FAU - Dekker, Jacqueline M AU - Dekker JM FAU - Kiechl, Stefan AU - Kiechl S FAU - Sitzer, Matthias AU - Sitzer M FAU - Bickel, Horst AU - Bickel H FAU - Rundek, Tatjana AU - Rundek T FAU - Hofman, Albert AU - Hofman A FAU - Mathiesen, Ellisiv B AU - Mathiesen EB FAU - Castelnuovo, Samuela AU - Castelnuovo S FAU - Landecho, Manuel F AU - Landecho MF FAU - Rosvall, Maria AU - Rosvall M FAU - Gabriel, Rafael AU - Gabriel R FAU - de Luca, Nicola AU - de Luca N FAU - Liu, Jing AU - Liu J FAU - Baldassarre, Damiano AU - Baldassarre D FAU - Kavousi, Maryam AU - Kavousi M FAU - de Groot, Eric AU - de Groot E FAU - Bots, Michiel L AU - Bots ML FAU - Yanez, David N AU - Yanez DN FAU - Thompson, Simon G AU - Thompson SG CN - PROG-IMT study group LA - eng PT - Journal Article PT - Published Erratum DEP - 20180920 PL - United States TA - PLoS One JT - PloS one JID - 101285081 EFR - PLoS One. 2018 Apr 12;13(4):e0191172. PMID: 29649236 PMC - PMC6147579 EDAT- 2018/09/21 06:00 MHDA- 2018/09/21 06:01 CRDT- 2018/09/21 06:00 PHST- 2018/09/21 06:00 [entrez] PHST- 2018/09/21 06:00 [pubmed] PHST- 2018/09/21 06:01 [medline] AID - 10.1371/journal.pone.0204633 [doi] AID - PONE-D-18-26761 [pii] PST - epublish SO - PLoS One. 2018 Sep 20;13(9):e0204633. doi: 10.1371/journal.pone.0204633. eCollection 2018. PMID- 29941600 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20190123 IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 115 IP - 28 DP - 2018 Jul 10 TI - Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth. PG - E6546-E6555 LID - 10.1073/pnas.1720113115 [doi] AB - The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid accumulation, which was attributable to an increased rate of fatty acid (FA) synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis in intratumoral Tregs, we demonstrated that both glycolytic and oxidative metabolism contribute to Tregs' expansion. We corroborated our data in human tumors showing that Tregs displayed a gene signature oriented toward glycolysis and lipid synthesis. Our data support a model in which signals from the tumor microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation that confers a preferential proliferative advantage to Tregs, whose targeting might represent a strategy for cancer treatment. FAU - Pacella, Ilenia AU - Pacella I AD - Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy. FAU - Procaccini, Claudio AU - Procaccini C AD - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy. FAU - Focaccetti, Chiara AU - Focaccetti C AD - Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy. FAU - Miacci, Stefano AU - Miacci S AD - Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy. FAU - Timperi, Eleonora AU - Timperi E AD - Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy. FAU - Faicchia, Deriggio AU - Faicchia D AD - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy. FAU - Severa, Martina AU - Severa M AD - Department of Infectious Diseases, Istituto Superiore di Sanita, 00161 Rome, Italy. FAU - Rizzo, Fabiana AU - Rizzo F AD - Department of Infectious Diseases, Istituto Superiore di Sanita, 00161 Rome, Italy. FAU - Coccia, Eliana Marina AU - Coccia EM AD - Department of Infectious Diseases, Istituto Superiore di Sanita, 00161 Rome, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20122 Milan, Italy. FAU - Mitro, Nico AU - Mitro N AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20122 Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20122 Milan, Italy. AD - Curtin Health Innovation Research Institute, School of Pharmacy and Biomedical Sciences, Curtin University, Perth, WA 6102, Australia. FAU - Rossetti, Grazisa AU - Rossetti G AUID- ORCID: 0000-0001-6361-311X AD - Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy. FAU - Ranzani, Valeria AU - Ranzani V AD - Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy. FAU - Pagani, Massimiliano AU - Pagani M AD - Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, 20122 Milan, Italy. AD - Department of Medical Biotechnology and Translational Medicine, Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Giorda, Ezio AU - Giorda E AD - Immunology Research Area, Ospedale Pediatrico Bambino Gesu Istituto di Ricovero e Cura a Carattere Scientifico, 00146 Rome, Italy. FAU - Wei, Yu AU - Wei Y AD - Laboratoire de Pathogenese des Virus de l'Hepatite B, Institut Pasteur, 75015 Paris, France. FAU - Matarese, Giuseppe AU - Matarese G AUID- ORCID: 0000-0001-9429-0616 AD - Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy; giuseppe.matarese@unina.it vincenzo.barnaba@uniroma1.it silvia.piconese@uniroma1.it. AD - Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita di Napoli Federico II, 80131 Naples, Italy. FAU - Barnaba, Vincenzo AU - Barnaba V AD - Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy; giuseppe.matarese@unina.it vincenzo.barnaba@uniroma1.it silvia.piconese@uniroma1.it. AD - Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy. AD - Center for Life Nano Science, Istituto Italiano di Tecnologia, 00161 Rome, Italy. FAU - Piconese, Silvia AU - Piconese S AD - Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy; giuseppe.matarese@unina.it vincenzo.barnaba@uniroma1.it silvia.piconese@uniroma1.it. AD - Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy. LA - eng GR - 310496/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180625 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Fatty Acids) RN - 0 (Neoplasm Proteins) RN - EC 2.3.1.85 (FASN protein, human) RN - EC 2.3.1.85 (Fatty Acid Synthase, Type I) SB - IM MH - Animals MH - Cell Line, Tumor MH - Fatty Acid Synthase, Type I/genetics/immunology MH - Fatty Acids/genetics/*immunology MH - Glycolysis/*immunology MH - Humans MH - Mice MH - Mice, Transgenic MH - Neoplasm Proteins/genetics/immunology MH - Neoplasms, Experimental/genetics/*immunology/pathology MH - Oxidation-Reduction MH - T-Lymphocytes, Regulatory/*immunology/pathology MH - Tumor Microenvironment/genetics/*immunology PMC - PMC6048537 OTO - NOTNLM OT - *Treg OT - *fatty acid synthesis OT - *glycolysis OT - *ox40 OT - *tumor microenvironment COIS- The authors declare no conflict of interest. EDAT- 2018/06/27 06:00 MHDA- 2018/09/11 06:00 CRDT- 2018/06/27 06:00 PHST- 2018/06/27 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2018/06/27 06:00 [entrez] AID - 1720113115 [pii] AID - 10.1073/pnas.1720113115 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):E6546-E6555. doi: 10.1073/pnas.1720113115. Epub 2018 Jun 25. PMID- 29967323 OWN - NLM STAT- In-Data-Review LR - 20181114 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Jul 2 TI - Cluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans. PG - 9979 LID - 10.1038/s41598-018-28019-3 [doi] AB - Ex vivo expansion and differentiation of human pancreatic beta-cell are enabling steps of paramount importance for accelerating the development of therapies for diabetes. The success of regenerative strategies depends on their ability to reproduce the chemical and biophysical properties of the microenvironment in which beta-cells develop, proliferate and function. In this paper we focus on the biophysical properties of the extracellular environment and exploit the cluster-assembled zirconia substrates with tailored roughness to mimic the nanotopography of the extracellular matrix. We demonstrate that beta-cells can perceive nanoscale features of the substrate and can convert these stimuli into mechanotransductive processes which promote long-term in vitro human islet culture, thus preserving beta-cell differentiation and function. Proteomic and quantitative immunofluorescence analyses demonstrate that the process is driven by nanoscale topography, via remodelling of the actin cytoskeleton and nuclear architecture. These modifications activate a transcriptional program which stimulates an adaptive metabolic glucose response. Engineered cluster-assembled substrates coupled with proteomic approaches may provide a useful strategy for identifying novel molecular targets for treating diabetes mellitus and for enhancing tissue engineering in order to improve the efficacy of islet cell transplantation therapies. FAU - Galli, Alessandra AU - Galli A AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Maffioli, Elisa AU - Maffioli E AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Sogne, Elisa AU - Sogne E AUID- ORCID: http://orcid.org/0000-0003-2097-4358 AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. AD - Biological and Environmental Science and Engineering Division, KAUST, Jeddah, Saudi Arabia. FAU - Moretti, Stefania AU - Moretti S AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Di Cairano, Eliana Sara AU - Di Cairano ES AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Negri, Armando AU - Negri A AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Nonnis, Simona AU - Nonnis S AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Bonacina, Fabrizia AU - Bonacina F AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. FAU - Borghi, Francesca AU - Borghi F AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Podesta, Alessandro AU - Podesta A AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Bertuzzi, Federico AU - Bertuzzi F AD - Niguarda Hospital, Milan, Italy. FAU - Milani, Paolo AU - Milani P AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Lenardi, Cristina AU - Lenardi C AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. AD - CIMAINA and Dipartimento di Fisica, Universita degli Studi di Milano, via Celoria 16, 20133, Milan, Italy. FAU - Tedeschi, Gabriella AU - Tedeschi G AD - Dipartimento di Medicina Veterinaria, Universita degli Studi di Milano, via Celoria 10, 20133, Milan, Italy. AD - Fondazione Filarete, v.le Ortles 22/4, 20139, Milan, Italy. FAU - Perego, Carla AU - Perego C AUID- ORCID: http://orcid.org/0000-0003-3027-1779 AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, via Trentacoste 2, 20134, Milan, Italy. carla.perego@unimi.it. LA - eng PT - Journal Article DEP - 20180702 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 EIN - Sci Rep. 2018 Nov 27;8(1):17472. PMID: 30478348 PMC - PMC6028636 EDAT- 2018/07/04 06:00 MHDA- 2018/07/04 06:00 CRDT- 2018/07/04 06:00 PHST- 2017/11/21 00:00 [received] PHST- 2018/06/07 00:00 [accepted] PHST- 2018/07/04 06:00 [entrez] PHST- 2018/07/04 06:00 [pubmed] PHST- 2018/07/04 06:00 [medline] AID - 10.1038/s41598-018-28019-3 [doi] AID - 10.1038/s41598-018-28019-3 [pii] PST - epublish SO - Sci Rep. 2018 Jul 2;8(1):9979. doi: 10.1038/s41598-018-28019-3. PMID- 29897493 OWN - NLM STAT- In-Data-Review LR - 20180613 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 114 IP - 6 DP - 2018 May 1 TI - Trained immunity and cardiovascular disease: is it time for translation to humans? PG - e41-e42 LID - 10.1093/cvr/cvy043 [doi] FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. AD - Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy. AD - Curtin Health Innovation Research Institute, School of Pharmacy and Biomedical Sciences, Curtin University, Perth, WA, Australia. LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 EDAT- 2018/06/14 06:00 MHDA- 2018/06/14 06:00 CRDT- 2018/06/14 06:00 PHST- 2018/06/14 06:00 [entrez] PHST- 2018/06/14 06:00 [pubmed] PHST- 2018/06/14 06:00 [medline] AID - 4974437 [pii] AID - 10.1093/cvr/cvy043 [doi] PST - ppublish SO - Cardiovasc Res. 2018 May 1;114(6):e41-e42. doi: 10.1093/cvr/cvy043. PMID- 29649236 OWN - NLM STAT- MEDLINE DCOM- 20180709 LR - 20190329 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 4 DP - 2018 TI - Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration. PG - e0191172 LID - 10.1371/journal.pone.0191172 [doi] AB - AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. FAU - Lorenz, Matthias W AU - Lorenz MW AUID- ORCID: 0000-0002-7565-1751 AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany. FAU - Gao, Lu AU - Gao L AD - MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, United Kingdom. FAU - Ziegelbauer, Kathrin AU - Ziegelbauer K AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Medical Biotechnology and Translational Medicine, Universita degli Studi di Milano, Milano, Italy. AD - SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Empana, Jean Philippe AU - Empana JP AD - Paris Cardiovascular Research Centre (PARCC), University Paris Descartes, Sorbonne Paris Cite, UMR, Paris, France. FAU - Schmidtmann, Irene AU - Schmidtmann I AD - Institut fuer Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Universitaetsmedizin Mainz, Mainz, Germany. FAU - Lin, Hung-Ju AU - Lin HJ AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - McLachlan, Stela AU - McLachlan S AD - Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom. FAU - Bokemark, Lena AU - Bokemark L AD - Wallenberg Laboratory for Cardiovascular Research, Institution for Medicin, Department for Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. FAU - Ronkainen, Kimmo AU - Ronkainen K AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. FAU - Amato, Mauro AU - Amato M AD - Centro Cardiologico Monzino, IRCCS, Milano, Italy. FAU - Schminke, Ulf AU - Schminke U AD - Department of Neurology, Greifswald University Clinic, Greifswald, Germany. FAU - Srinivasan, Sathanur R AU - Srinivasan SR AD - Center for Cardiovascular Health, Department of Epidemiology, Biochemistry, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America. FAU - Lind, Lars AU - Lind L AD - Department of Medicine, Uppsala University, Uppsala, Sweden. FAU - Okazaki, Shuhei AU - Okazaki S AD - Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan. FAU - Stehouwer, Coen D A AU - Stehouwer CDA AD - Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, the Netherlands. FAU - Willeit, Peter AU - Willeit P AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. AD - Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. FAU - Polak, Joseph F AU - Polak JF AD - Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America. FAU - Steinmetz, Helmuth AU - Steinmetz H AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany. FAU - Sander, Dirk AU - Sander D AD - Department of Neurology, Benedictus Hospital Tutzing & Feldafing, Feldafing, Germany. FAU - Poppert, Holger AU - Poppert H AD - Department of Neurology, Technische Universitat Munchen, Munich, Germany. FAU - Desvarieux, Moise AU - Desvarieux M AD - Department of Epidemiology,Mailman School of Public Health,Columbia University, New York, United States of America. FAU - Ikram, M Arfan AU - Ikram MA AD - Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. AD - Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands. AD - Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Johnsen, Stein Harald AU - Johnsen SH AD - Department of Clinical Medicine, Uit The Arctic University of Norway, Tromso, Norway. AD - Department of Neurology, University Hospital of Northern Norway, Tromso, Norway. FAU - Staub, Daniel AU - Staub D AD - Department of Angiology, University Hospital Basel, Basel, Switzerland. FAU - Sirtori, Cesare R AU - Sirtori CR AD - Center of Dyslipidemias, Niguarda Ca' Granda Hospital, Milano, Italy. FAU - Iglseder, Bernhard AU - Iglseder B AD - Parcelsus Medical University, Salzburg, Austria. AD - Department of Geriatric Medicine, Gemeinnutzige Salzburger Landeskliniken Betriebsgesellschaft GmbH Christian-Doppler-Klinik, Salzburg, Austria. FAU - Beloqui, Oscar AU - Beloqui O AD - Department of Internal Medicine, University Clinic of Navarra, Navarra, Spain. FAU - Engstrom, Gunnar AU - Engstrom G AD - Department of Clinical Sciences in Malmo, Lund University, Malmo, Sweden. FAU - Friera, Alfonso AU - Friera A AD - Radiology Department, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Rozza, Francesco AU - Rozza F AD - School of Medicine, Federico II University, Naples, Italy. FAU - Xie, Wuxiang AU - Xie W AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases,Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Parraga, Grace AU - Parraga G AD - Robarts Research Institute, Western University, London, Ontario, Canada. FAU - Grigore, Liliana AU - Grigore L AD - Centro Sisa per lo Studio della Aterosclerosi, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Plichart, Matthieu AU - Plichart M AD - Assistance Publique, Hopitaux de Paris, Hopital Broca, Paris, France. FAU - Blankenberg, Stefan AU - Blankenberg S AD - 2nd Department of Medicine, Johannes Gutenberg-Universitat, Mainz, Germany. AD - Department of Cardiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. FAU - Su, Ta-Chen AU - Su TC AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Schmidt, Caroline AU - Schmidt C AD - Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Gothenburg, Sweden. FAU - Tuomainen, Tomi-Pekka AU - Tuomainen TP AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. FAU - Veglia, Fabrizio AU - Veglia F AD - Centro Cardiologico Monzino, IRCCS, Milano, Italy. FAU - Volzke, Henry AU - Volzke H AD - German Center for Cardiovascular Research (DZHK),partner site Greifswald, Greifswald, Germany. AD - Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, Greifswald, Germany. FAU - Nijpels, Giel AU - Nijpels G AD - Department of General Practice, VU University Medical Center, Amsterdam, the Netherlands. AD - EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands. 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, Florida, United States of America. FAU - Franco, Oscar H AU - Franco OH AD - Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. FAU - Uthoff, Heiko AU - Uthoff H AD - Department of Angiology, University Hospital Basel, Basel, Switzerland. FAU - Hedblad, Bo AU - Hedblad B AD - Department of Clinical Sciences in Malmo, Lund University, Malmo, Sweden. FAU - Suarez, Carmen AU - Suarez C AD - Internal Medicine Department, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain. FAU - Izzo, Raffaele AU - Izzo R AD - School of Medicine, Federico II University, Naples, Italy. FAU - Zhao, Dong AU - Zhao D AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases,Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Wannarong, Thapat AU - Wannarong T AD - Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada. AD - Department of Internal Medicine, Faculty of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. FAU - Catapano, Alberico AU - Catapano A AD - IRCSS Multimedica, Milan, Italy. AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. FAU - Ducimetiere, Pierre AU - Ducimetiere P AD - University Paris_Sud Xi, Kremlin-Bicetre, Le Kremlin-Bicetre, France. FAU - Espinola-Klein, Christine AU - Espinola-Klein C AD - 2nd Department of Medicine, Johannes-Gutenberg University, Mainz, Germany. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, College of Public Health,National Taiwan University, Taipei, Taiwan. FAU - Price, Jackie F AU - Price JF AD - Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom. FAU - Bergstrom, Goran AU - Bergstrom G AD - Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gotheborg, Sweden. FAU - Kauhanen, Jussi AU - Kauhanen J AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. FAU - Tremoli, Elena AU - Tremoli E AD - Department of Medical Biotechnology and Translational Medicine, Universita degli Studi di Milano, Milano, Italy. AD - Centro Cardiologico Monzino, IRCCS, Milano, Italy. FAU - Dorr, Marcus AU - Dorr M AD - Department B for Internal Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Berenson, Gerald AU - Berenson G AD - Department of Medicine, Pediatrics, Biochemistry, Epidemiology, Tulane University School of Medicine and School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America. FAU - Kitagawa, Kazuo AU - Kitagawa K AD - Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan. FAU - Dekker, Jacqueline M AU - Dekker JM AD - Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. FAU - Sitzer, Matthias AU - Sitzer M AD - Department of Neuology, Klinikum Herford, Herford, Germany. FAU - Bickel, Horst AU - Bickel H AD - Department of Psychiatry and Psychotherapy, Technische Universitat Munchen, Munich, Germany. FAU - Rundek, Tatjana AU - Rundek T AD - Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida, United States of America. FAU - Hofman, Albert AU - Hofman A AD - Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Mathiesen, Ellisiv B AU - Mathiesen EB AD - Department of Clinical Medicine, Uit The Arctic University of Norway, Tromso, Norway. FAU - Castelnuovo, Samuela AU - Castelnuovo S AD - Center of Dyslipidemias, Niguarda Ca' Granda Hospital, Milano, Italy. FAU - Landecho, Manuel F AU - Landecho MF AD - Department of Internal Medicine, University Clinic of Navarra, Navarra, Spain. FAU - Rosvall, Maria AU - Rosvall M AD - Department of Clinical Sciences in Malmo, Lund University, Malmo, Sweden. FAU - Gabriel, Rafael AU - Gabriel R AD - Escuela National de Sanidad, Instituto de Salud Carlos III, Madrid, Spain. FAU - de Luca, Nicola AU - de Luca N AD - School of Medicine, Federico II University, Naples, Italy. FAU - Liu, Jing AU - Liu J AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases,Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Baldassarre, Damiano AU - Baldassarre D AD - Department of Medical Biotechnology and Translational Medicine, Universita degli Studi di Milano, Milano, Italy. AD - Centro Cardiologico Monzino, IRCCS, Milano, Italy. FAU - Kavousi, Maryam AU - Kavousi M AD - Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands. FAU - de Groot, Eric AU - de Groot E AD - Imagelabonline & Cardiovascular, Eindhoven and Lunteren, the Netherlands. AD - Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, the Netherlands. FAU - Bots, Michiel L AU - Bots ML AD - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. FAU - Yanez, David N AU - Yanez DN AD - Department of Biostatistics, University of Washington, Seattle, Washington, United States of America. FAU - Thompson, Simon G AU - Thompson SG AD - Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. CN - PROG-IMT study group LA - eng GR - RG/13/13/30194/British Heart Foundation/United Kingdom GR - R01 AG015928/AG/NIA NIH HHS/United States 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 - R56 AG020098/AG/NIA 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 - R37 NS029993/NS/NINDS NIH HHS/United States GR - HHSN268201200036C/HL/NHLBI NIH HHS/United States GR - R01 HL080295/HL/NHLBI NIH HHS/United States GR - R01 AG020098/AG/NIA NIH HHS/United States GR - N01HC75150/HL/NHLBI 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 - N01 HC035129/HC/NHLBI NIH HHS/United States GR - R56 AG023629/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180412 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM EIN - PLoS One. 2018 Sep 20;13(9):e0204633. PMID: 30235339 MH - Aged MH - Cardiovascular Diseases/*diagnosis/diagnostic imaging/epidemiology MH - *Carotid Intima-Media Thickness MH - Female MH - Humans MH - *Intersectoral Collaboration MH - Male MH - Middle Aged MH - Prognosis MH - Risk Factors PMC - PMC5896895 EDAT- 2018/04/13 06:00 MHDA- 2018/07/10 06:00 CRDT- 2018/04/13 06:00 PHST- 2017/09/29 00:00 [received] PHST- 2017/11/29 00:00 [accepted] PHST- 2018/04/13 06:00 [entrez] PHST- 2018/04/13 06:00 [pubmed] PHST- 2018/07/10 06:00 [medline] AID - 10.1371/journal.pone.0191172 [doi] AID - PONE-D-17-35265 [pii] PST - epublish SO - PLoS One. 2018 Apr 12;13(4):e0191172. doi: 10.1371/journal.pone.0191172. eCollection 2018. PMID- 28603045 OWN - NLM STAT- MEDLINE DCOM- 20180405 LR - 20180405 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 810 DP - 2017 Sep 5 TI - Arctigenin improves vascular tone and decreases inflammation in human saphenous vein. PG - 51-56 LID - S0014-2999(17)30399-0 [pii] LID - 10.1016/j.ejphar.2017.06.004 [doi] AB - The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100muM) separated with an incubation period of 30min without (Control) or with ATG (3-100muM) were established. Inhibitors of nitric oxide, prostaglandins, K(+) related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti-inflammatory actions, SV were treated with 10muM or 100muM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators Interleukine-1 beta (IL-1beta), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- alpha (TNF-alpha), Interleukine-6 (IL-6), Prostaglandin E2 (PGE2) and Interleukine-8 (IL-8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl2. The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100microM). ATG reduces contractions in SV and decreases the production of proinflammatory-proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Daci, Armond AU - Daci A AD - Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo; Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. FAU - Neziri, Burim AU - Neziri B AD - Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. FAU - Krasniqi, Shaip AU - Krasniqi S AD - Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. Electronic address: shaip.krasniqi@uni-pr.edu. FAU - Cavolli, Raif AU - Cavolli R AD - Cardiovascular Surgery Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo. FAU - Alaj, Rame AU - Alaj R AD - Cardiovascular Surgery Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Science, Curtin University, Perth, Western Australia, Australia. FAU - Beretta, Giangiacomo AU - Beretta G AD - Department of Environmental Science and Policy, Universita degli Studi di Milano, Milan, Italy. LA - eng PT - Journal Article DEP - 20170608 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Furans) RN - 0 (Inflammation Mediators) RN - 0 (Lignans) RN - U76MR9VS6M (arctigenin) SB - IM MH - Anti-Inflammatory Agents/*pharmacology/therapeutic use MH - Dose-Response Relationship, Drug MH - Furans/*pharmacology/therapeutic use MH - Humans MH - Inflammation/drug therapy/metabolism/physiopathology MH - Inflammation Mediators/metabolism MH - Lignans/*pharmacology/therapeutic use MH - Saphenous Vein/*drug effects/metabolism/*physiopathology MH - Vascular Resistance/drug effects MH - Vasodilation/drug effects OTO - NOTNLM OT - Arctigenin OT - Coronary artery bypass graft OT - Human saphenous vein OT - Inflammation OT - Vascular tone EDAT- 2017/06/13 06:00 MHDA- 2018/04/06 06:00 CRDT- 2017/06/13 06:00 PHST- 2017/05/01 00:00 [received] PHST- 2017/05/31 00:00 [revised] PHST- 2017/06/02 00:00 [accepted] PHST- 2017/06/13 06:00 [pubmed] PHST- 2018/04/06 06:00 [medline] PHST- 2017/06/13 06:00 [entrez] AID - S0014-2999(17)30399-0 [pii] AID - 10.1016/j.ejphar.2017.06.004 [doi] PST - ppublish SO - Eur J Pharmacol. 2017 Sep 5;810:51-56. doi: 10.1016/j.ejphar.2017.06.004. Epub 2017 Jun 8. PMID- 28592702 OWN - NLM STAT- MEDLINE DCOM- 20170828 LR - 20170828 IS - 1470-8736 (Electronic) IS - 0143-5221 (Linking) VI - 131 IP - 12 DP - 2017 Jun 15 TI - A past and present overview of macrophage metabolism and functional outcomes. PG - 1329-1342 LID - 10.1042/CS20170220 [doi] AB - In 1986 and 1987, Philip Newsholme et al. reported macrophages utilize glutamine, as well as glucose, at high rates. These authors measured key enzyme activities and consumption and production levels of metabolites in incubated or cultured macrophages isolated from the mouse or rat intraperitoneal cavity. Metabolic pathways essential for macrophage function were then determined. Macrophages utilize glucose to generate (i) ATP in the pathways of glycolysis and mitochondrial oxidative phosphorylation, (ii) glycerol 3-phosphate for the synthesis of phospholipids and triacylglycerols, (iii) NADPH for the production of reactive oxygen species (ROS) and (iv) ribose for the synthesis of RNA and subsequently production and secretion of protein mediators (e.g. cytokines). Glutamine plays an essential role in macrophage metabolism and function, as it is required for energy production but also provides nitrogen for synthesis of purines, pyrimidines and thus RNA. Macrophages also utilize fatty acids for both energy production in the mitochondria and lipid synthesis essential to plasma membrane turnover and lipid meditator production. Recent studies utilizing metabolomic approaches, transcriptional and metabolite tracking technologies have detailed mitochondrial release of tricarboxylic acid (TCA) intermediates (e.g. citrate and succinate) to the cytosol, which then regulate pro-inflammatory responses. Macrophages can reprogramme their metabolism and function according to environmental conditions and stimuli in order to polarize phenotype so generating pro- or anti-inflammatory cells. Changes in macrophage metabolism result in modified function/phenotype and vice versa. The plasticity of macrophage metabolism allows the cell to quickly respond to changes in environmental conditions such as those induced by hormones and/or inflammation. A past and present overview of macrophage metabolism and impact of endocrine regulation and the relevance to human disease are described in this review. CI - (c) 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society. FAU - Curi, Rui AU - Curi R AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524, SP 05508-900, Brazil. FAU - de Siqueira Mendes, Renata AU - de Siqueira Mendes R AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524, SP 05508-900, Brazil. FAU - de Campos Crispin, Luiz Aurelio AU - de Campos Crispin LA AD - Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, SP 05503-900, Sao Paulo, Brazil. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute (CHIRI), Curtin University, Perth, WA, Australia. AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Sampaio, Sandra Coccuzzo AU - Sampaio SC AD - Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brazil, 1500, SP 05503-900, Sao Paulo, Brazil. AD - Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1524, SP 05508-900, Brazil. FAU - Newsholme, Philip AU - Newsholme P AD - School of Biomedical Sciences, Curtin Health Innovation Research Institute (CHIRI), Curtin University, Perth, WA, Australia Philip.Newsholme@curtin.edu.au. LA - eng PT - Journal Article PT - Review PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 0 (Fatty Acids) RN - 0RH81L854J (Glutamine) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - *Cell Plasticity MH - Cellular Microenvironment MH - *Energy Metabolism MH - Fatty Acids/metabolism MH - Glucose/metabolism MH - Glutamine/metabolism MH - Humans MH - *Macrophage Activation MH - Macrophages/immunology/*metabolism/pathology MH - Phenotype MH - Signal Transduction OTO - NOTNLM OT - fatty acids OT - glucocorticoids OT - glucose OT - glutamine OT - inflammasomes OT - inflammation OT - insulin OT - lipids OT - macrophages OT - thyroid hormones EDAT- 2017/06/09 06:00 MHDA- 2017/08/29 06:00 CRDT- 2017/06/09 06:00 PHST- 2017/03/16 00:00 [received] PHST- 2017/03/16 00:00 [revised] PHST- 2017/03/22 00:00 [accepted] PHST- 2017/06/09 06:00 [entrez] PHST- 2017/06/09 06:00 [pubmed] PHST- 2017/08/29 06:00 [medline] AID - CS20170220 [pii] AID - 10.1042/CS20170220 [doi] PST - ppublish SO - Clin Sci (Lond). 2017 Jun 15;131(12):1329-1342. doi: 10.1042/CS20170220. PMID- 28572395 OWN - NLM STAT- MEDLINE DCOM- 20180117 LR - 20180117 IS - 1095-9203 (Electronic) IS - 0036-8075 (Linking) VI - 356 IP - 6341 DP - 2017 Jun 2 TI - mTORC1 activity repression by late endosomal phosphatidylinositol 3,4-bisphosphate. PG - 968-972 LID - 10.1126/science.aaf8310 [doi] AB - Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane. We investigated mechanisms that repress mTORC1 under conditions of growth factor deprivation. We identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], synthesized by class II PI3K beta (PI3KC2beta) at LyLEs, as a negative regulator of mTORC1, whereas loss of PI3KC2beta hyperactivated mTORC1. Growth factor deprivation induced the association of PI3KC2beta with the Raptor subunit of mTORC1. Local PI(3,4)P2 synthesis triggered repression of mTORC1 activity through association of Raptor with inhibitory 14-3-3 proteins. These results unravel an unexpected function for local PI(3,4)P2 production in shutting off mTORC1. CI - Copyright (c) 2017, American Association for the Advancement of Science. FAU - Marat, Andrea L AU - Marat AL AUID- ORCID: 0000-0001-8571-4253 AD - Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, Robert-Roessle-Strasse 10, 13125 Berlin, Germany. FAU - Wallroth, Alexander AU - Wallroth A AUID- ORCID: 0000-0002-1086-0544 AD - Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, Robert-Roessle-Strasse 10, 13125 Berlin, Germany. FAU - Lo, Wen-Ting AU - Lo WT AUID- ORCID: 0000-0001-7904-6834 AD - Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, Robert-Roessle-Strasse 10, 13125 Berlin, Germany. FAU - Muller, Rainer AU - Muller R AUID- ORCID: 0000-0003-3464-494X AD - European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy. AD - Curtin Health Innovation Research Institute, School of Biomedical Sciences, Curtin University, Perth, Western Australia, Australia. FAU - Falasca, Marco AU - Falasca M AUID- ORCID: 0000-0002-9801-7235 AD - Curtin Health Innovation Research Institute, School of Biomedical Sciences, Curtin University, Perth, Western Australia, Australia. FAU - Schultz, Carsten AU - Schultz C AD - European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany. FAU - Haucke, Volker AU - Haucke V AUID- ORCID: 0000-0003-3119-6993 AD - Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, Robert-Roessle-Strasse 10, 13125 Berlin, Germany. haucke@fmp-berlin.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (14-3-3 Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Phosphatidylinositol Phosphates) RN - 0 (Regulatory-Associated Protein of mTOR) RN - 0 (phosphatidylinositol 3,4-diphosphate) RN - EC 2.7.1.137 (Class II Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) SB - IM CIN - EMBO J. 2017 Jul 3;36(13):1809-1810. PMID: 28623241 MH - 14-3-3 Proteins/metabolism MH - Animals MH - COS Cells MH - Cells, Cultured MH - Cercopithecus aethiops MH - Class II Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Endosomes/*enzymology MH - Enzyme Activation/physiology MH - Fibroblasts MH - Gene Knockout Techniques MH - HEK293 Cells MH - HeLa Cells MH - Humans MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Lysosomes/*enzymology MH - Mechanistic Target of Rapamycin Complex 1/*metabolism MH - Mice MH - Phosphatidylinositol Phosphates/*metabolism MH - Protein Transport/genetics MH - Regulatory-Associated Protein of mTOR/metabolism MH - Signal Transduction/genetics EDAT- 2017/06/03 06:00 MHDA- 2018/01/18 06:00 CRDT- 2017/06/03 06:00 PHST- 2016/04/06 00:00 [received] PHST- 2016/11/22 00:00 [revised] PHST- 2017/05/08 00:00 [accepted] PHST- 2017/06/03 06:00 [entrez] PHST- 2017/06/03 06:00 [pubmed] PHST- 2018/01/18 06:00 [medline] AID - 356/6341/968 [pii] AID - 10.1126/science.aaf8310 [doi] PST - ppublish SO - Science. 2017 Jun 2;356(6341):968-972. doi: 10.1126/science.aaf8310. PMID- 28377556 OWN - NLM STAT- MEDLINE DCOM- 20180823 LR - 20181202 IS - 1897-9483 (Electronic) IS - 0032-3772 (Linking) VI - 127 IP - 3 DP - 2017 Mar 31 TI - Long pentraxin PTX3 as a prognostic marker of cardiovascular mortality in patients with chronic kidney disease. PG - 152-153 LID - 10.20452/pamw.3989 [doi] FAU - Baragetti, Andrea AU - Baragetti A FAU - Norata, Giuseppe D AU - Norata GD LA - eng PT - Editorial PT - Comment DEP - 20170331 PL - Poland TA - Pol Arch Intern Med JT - Polish archives of internal medicine JID - 101700960 RN - 0 (Serum Amyloid P-Component) RN - 9007-41-4 (C-Reactive Protein) SB - IM CON - Pol Arch Intern Med. 2017 Feb 27;127(3):170-177. PMID: 28377558 MH - *C-Reactive Protein MH - Cardiovascular Diseases MH - Humans MH - Prognosis MH - Renal Insufficiency, Chronic MH - *Serum Amyloid P-Component EDAT- 2017/04/06 06:00 MHDA- 2018/08/24 06:00 CRDT- 2017/04/06 06:00 PHST- 2017/04/06 06:00 [entrez] PHST- 2017/04/06 06:00 [pubmed] PHST- 2018/08/24 06:00 [medline] AID - 10.20452/pamw.3989 [doi] PST - ppublish SO - Pol Arch Intern Med. 2017 Mar 31;127(3):152-153. doi: 10.20452/pamw.3989. Epub 2017 Mar 31. PMID- 28297661 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20181113 IS - 2211-1247 (Electronic) VI - 18 IP - 11 DP - 2017 Mar 14 TI - T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP. PG - 2566-2575 LID - S2211-1247(17)30276-0 [pii] LID - 10.1016/j.celrep.2017.02.061 [doi] AB - The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help. CI - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Perruzza, Lisa AU - Perruzza L AD - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 6500 Bellinzona, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3001 Bern 9, Switzerland. FAU - Gargari, Giorgio AU - Gargari G AD - Department of Food, Environmental, and Nutritional Sciences (DeFENS), Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Proietti, Michele AU - Proietti M AD - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 6500 Bellinzona, Switzerland. FAU - Fosso, Bruno AU - Fosso B AD - Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy. FAU - D'Erchia, Anna Maria AU - D'Erchia AM AD - Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70126 Bari, Italy. FAU - Faliti, Caterina Elisa AU - Faliti CE AD - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 6500 Bellinzona, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3001 Bern 9, Switzerland. FAU - Rezzonico-Jost, Tanja AU - Rezzonico-Jost T AD - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 6500 Bellinzona, Switzerland. FAU - Scribano, Daniela AU - Scribano D AD - Department of Medical and Oral Sciences and Biotechnologies, University "Gabriele D'Annunzio", 66100 Chieti, Italy; Departement of Public Health and Infectious Diseases, University "La Sapienza" of Rome, 00185 Rome, Italy. FAU - Mauri, Laura AU - Mauri L AD - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, 20129 Milan, Italy. FAU - Colombo, Diego AU - Colombo D AD - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, 20129 Milan, Italy. FAU - Pellegrini, Giovanni AU - Pellegrini G AD - Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland. FAU - Moregola, Annalisa AU - Moregola A AD - Department of Pharmacological and Biomolecular Sciences (DiSFeB), Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Mooser, Catherine AU - Mooser C AD - Maurice Muller Laboratories, Universitatsklinik fur Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland. FAU - Pesole, Graziano AU - Pesole G AD - Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70126 Bari, Italy. FAU - Nicoletti, Mauro AU - Nicoletti M AD - Department of Medical and Oral Sciences and Biotechnologies, University "Gabriele D'Annunzio", 66100 Chieti, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences (DiSFeB), Universita degli Studi di Milano, 20133 Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6845, Australia. FAU - Geuking, Markus B AU - Geuking MB AD - Maurice Muller Laboratories, Universitatsklinik fur Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland; Department of Microbiology, Immunology and Infectious Diseases and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. FAU - McCoy, Kathy D AU - McCoy KD AD - Maurice Muller Laboratories, Universitatsklinik fur Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland; Department of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. FAU - Guglielmetti, Simone AU - Guglielmetti S AD - Department of Food, Environmental, and Nutritional Sciences (DeFENS), Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Grassi, Fabio AU - Grassi F AD - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 6500 Bellinzona, Switzerland; Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita degli Studi di Milano, 20129 Milan, Italy; Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy. Electronic address: fabio.grassi@irb.usi.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Immunoglobulin A) RN - 0 (P2rx7 protein, mouse) RN - 0 (Receptors, Purinergic P2X7) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adenosine Triphosphate/*metabolism MH - Animals MH - Body Weight MH - Extracellular Space/*metabolism MH - Gastrointestinal Microbiome/*immunology MH - Glucose/metabolism MH - *Homeostasis MH - Immunoglobulin A/metabolism MH - Intestine, Small/microbiology MH - Mice, Inbred C57BL MH - Receptors, Purinergic P2X7/deficiency/metabolism MH - T-Lymphocytes, Helper-Inducer/*immunology PMC - PMC5368345 OTO - NOTNLM OT - *ATP OT - *IgA OT - *P2rx7 OT - *T follicular helper cells OT - *metabolism OT - *microbiota EDAT- 2017/03/16 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/03/16 06:00 PHST- 2016/08/08 00:00 [received] PHST- 2017/01/24 00:00 [revised] PHST- 2017/02/17 00:00 [accepted] PHST- 2017/03/16 06:00 [entrez] PHST- 2017/03/16 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] AID - S2211-1247(17)30276-0 [pii] AID - 10.1016/j.celrep.2017.02.061 [doi] PST - ppublish SO - Cell Rep. 2017 Mar 14;18(11):2566-2575. doi: 10.1016/j.celrep.2017.02.061. PMID- 27627804 OWN - NLM STAT- MEDLINE DCOM- 20170802 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 9 DP - 2016 TI - Epicardial Adipose Tissue (EAT) Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease. PG - e0162473 LID - 10.1371/journal.pone.0162473 [doi] AB - BACKGROUND AND AIMS: Epicardial adipose tissue (EAT) has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD). Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1) the association between EAT, the other metabolic parameters and the severity of steatosis 2) the relationship between cardiovascular (cIMT, cplaques, E/A), liver (presence of NASH and significant fibrosis) damage and metabolic risk factors including EAT 3) the relationship between EAT and genetic factors strongly influencing liver steatosis. METHODS: In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100). EAT, severity of steatosis, carotid intima-media thickness (cIMT) and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm) were female gender (p = 0.003), age (p = 0.001), BMI (p = 0.01), diastolic blood pressure (p = 0.009), steatosis grade 2 (p = 0.01) and 3 (p = 0.04), fatty liver index (p = 0.001) and statin use (p = 0.03). Variables independently associated with carotid IMT were age (p = 0.0001), hypertension (p = 0.009), diabetes (p = 0.04), smoking habits (p = 0.04) and fatty liver index (p = 0.02), with carotid plaques age (p = 0.0001), BMI (p = 0.03), EAT (p = 0.02),) and hypertension (p = 0.02), and with E/A age (p = 0.0001), diabetes (p = 0.005), hypertension (p = 0.04) and fatty liver index (p = 0.004). In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH) was independently associated with EAT (p = 0.04) and diabetes (p = 0.054) while significant fibrosis with EAT (p = 0.02), diabetes (p = 0.01) and waist circumference (p = 0.05). No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found. CONCLUSION: In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors. FAU - Fracanzani, Anna Ludovica AU - Fracanzani AL AUID- ORCID: http://orcid.org/0000-0001-5918-0171 AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Pisano, Giuseppina AU - Pisano G AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Consonni, Dario AU - Consonni D AD - Epidemiology Unit, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Tiraboschi, Silvia AU - Tiraboschi S AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and Centro Studi Aterosclerosi Milan, Milan, Italy. FAU - Bertelli, Cristina AU - Bertelli C AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan and Centro Studi Aterosclerosi Milan, Milan, Italy. FAU - Dongiovanni, Paola AU - Dongiovanni P AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Valenti, Luca AU - Valenti L AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. FAU - Grigore, Liliana AU - Grigore L AD - Centro Studi Aterosclerosi, Bassini Hospital, Milan, Italy. FAU - Tonella, Tatiana AU - Tonella T AD - Cardiovascular Medicine Unit, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, Milan, Italy. FAU - Catapano, Alberico AU - Catapano A AD - Department of Pharmacological and Biomolecular Sciences, University of Milano, and Multimedica IRCCS, Milan, Italy. FAU - Fargion, Silvia AU - Fargion S AD - Department of Pathophysiology and Transplantation, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. LA - eng PT - Journal Article DEP - 20160914 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Adipose Tissue/*pathology MH - Aged MH - Cardiovascular Diseases/*pathology MH - Cross-Sectional Studies MH - Female MH - Humans MH - Liver/*pathology MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/*pathology MH - Pericardium/*pathology PMC - PMC5023162 COIS- The authors have declared that no competing interests exist. EDAT- 2016/09/15 06:00 MHDA- 2017/08/03 06:00 CRDT- 2016/09/15 06:00 PHST- 2016/06/03 00:00 [received] PHST- 2016/08/23 00:00 [accepted] PHST- 2016/09/15 06:00 [entrez] PHST- 2016/09/15 06:00 [pubmed] PHST- 2017/08/03 06:00 [medline] AID - 10.1371/journal.pone.0162473 [doi] AID - PONE-D-16-20141 [pii] PST - epublish SO - PLoS One. 2016 Sep 14;11(9):e0162473. doi: 10.1371/journal.pone.0162473. eCollection 2016. PMID- 26746227 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20181002 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 23 IP - 11 DP - 2016 Jul TI - Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin? PG - 1165-73 LID - 10.1177/2047487315625543 [doi] AB - BACKGROUND: The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. DESIGN: Meta-analysis of individual participant data. METHOD: From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. RESULTS: Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. CONCLUSIONS: The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions. CI - (c) The European Society of Cardiology 2016. FAU - Liao, Ximing AU - Liao X AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany. FAU - Norata, Giuseppe D AU - Norata GD AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Polak, Joseph F AU - Polak JF AD - Tufts University School of Medicine, Tufts Medical Center, Boston, USA. FAU - Stehouwer, Coen DA AU - Stehouwer CD AD - Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, The Netherlands. FAU - Catapano, Alberico AU - Catapano A AD - IRCSS Multimedica, Milan, Italy Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy. FAU - Rundek, Tatjana AU - Rundek T AD - Department of Neurology, Miller School of Medicine, University of Miami, USA. FAU - Ezhov, Marat AU - Ezhov M AD - Atherosclerosis Department, Cardiology Research Centre, Moscow, Russia. FAU - Sander, Dirk AU - Sander D AD - Department of Neurology, Benedictus Hospital Tutzing & Feldafing, Feldafing, Germany Department of Neurology, Technische Universitat Munchen, Germany. FAU - Thompson, Simon G AU - Thompson SG AD - Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, UK. FAU - Lorenz, Matthias W AU - Lorenz MW AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany matthias.lorenz@em.uni-frankfurt.de. CN - PROG-IMT study group FAU - Balakhonova, Tatyana AU - Balakhonova T AD - Ultrasound Vascular Laboratory, Cardiology Research Centre2, Moscow, Russia. FAU - Safarova, Maya AU - Safarova M AD - Atherosclerosis Department, Cardiology Research Centre, Moscow, Russia. FAU - Grigore, Liliana AU - Grigore L AD - SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Empana, Jean-Philippe AU - Empana JP AD - Paris Cardiovascular Research Centre (PARCC), University Paris Descartes, Sorbonne Paris Cite, France. FAU - Lin, Hung-Ju AU - Lin HJ AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - McLachlan, Stela AU - McLachlan S AD - Centre for Population Health Sciences, University of Edinburgh, UK. FAU - Bokemark, Lena AU - Bokemark L AD - Wallenberg Laboratory for Cardiovascular Research, Institution for Medicin, Department for Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Sweden. FAU - Ronkainen, Kimmo AU - Ronkainen K AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Schminke, Ulf AU - Schminke U AD - Department of Neurology, Greifswald University Clinic, Germany. FAU - Lind, Lars AU - Lind L AD - Department of Medicine, Uppsala University, Sweden. FAU - Willeit, Peter AU - Willeit P AD - Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, UK Department of Neurology, Medical University Innsbruck, Austria. FAU - Yanez, David N AU - Yanez DN AD - Department of Biostatistics, University of Washington, Seattle, USA. FAU - Steinmetz, Helmuth AU - Steinmetz H AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany. FAU - Poppert, Holger AU - Poppert H AD - Department of Neurology, Technische Universitat Munchen, Germany. FAU - Desvarieux, Moise AU - Desvarieux M AD - Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA. FAU - Ikram, M Arfan AU - Ikram MA AD - Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Johnsen, Stein Harald AU - Johnsen SH AD - Department of Clinical Medicine, University of Tromso, Norway Department of Neurology, University Hospital of Northern Norway, Tromso, Norway. FAU - Iglseder, Bernhard AU - Iglseder B AD - Parcelsus Medical University, Salzburg, Austria Department of Geriatric Medicine, Gemeinnutzige Salzburger Landeskliniken Betriebsgesellschaft GmbH Christian-Doppler-Klinik, Salzburg, Austria. FAU - Friera, Alfonsa AU - Friera A AD - Radiology Department, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Spain. FAU - Xie, Wuxiang AU - Xie W AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, China. FAU - Plichart, Matthieu AU - Plichart M AD - Assistance Publique, Hopitaux de Paris, Hopital Broca, Paris, France. FAU - Su, Ta-Chen AU - Su TC AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Srinivasan, Sathanur R AU - Srinivasan SR AD - Center for Cardiovascular Health, Department of Epidemiology, Biochemistry, Tulane University School of Public Health and Tropical Medicine, New Orleans, USA. FAU - Schmidt, Caroline AU - Schmidt C AD - Wallenberg Laboratory for Cardiovascular Research, Institution for Medicin, Department for Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Sweden. FAU - Tuomainen, Tomi-Pekka AU - Tuomainen TP AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Volzke, Henry AU - Volzke H AD - Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, Greifswald, Germany. FAU - Nijpels, Giel AU - Nijpels G AD - Department of General Practice, VU University Medical Centre, Amsterdam, The Netherlands EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. FAU - Willeit, Johann AU - Willeit J AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Franco, Oscar H AU - Franco OH AD - Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Suarez, Carmen AU - Suarez C AD - Internal Medicine Department, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Spain. FAU - Zhao, Dong AU - Zhao D AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, China. FAU - Ducimetiere, Pierre AU - Ducimetiere P AD - University Paris Sud Xi, Kremlin-Bicetre, Le Kremlin-Bicetre, France. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Robertson, Christine AU - Robertson C AD - Centre for Population Health Sciences, University of Edinburgh, UK. FAU - Bergstrom, Goran AU - Bergstrom G AD - Wallenberg Laboratory for Cardiovascular Research, Institution for Medicin, Department for Molecular and Clinical Medicine, Sahlgrenska Academy, Gothenburg University, Sweden. FAU - Kauhanen, Jussi AU - Kauhanen J AD - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. FAU - Dorr, Marcus AU - Dorr M AD - Department B for Internal Medicine, University Medicine Greifswald, Germany German Centrefor Cardiovascular Research (DZHK), partner site Greifswald, Germany. FAU - Dekker, Jaqueline M AU - Dekker JM AD - Department of Epidemiology and Biostatistics, University Medical Centre, Amsterdam, The Netherlands. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University Innsbruck, Austria. FAU - Sitzer, Matthias AU - Sitzer M AD - Department of Neurology, Goethe University, Frankfurt am Main, Germany Department of Neurology, Klinikum Herford, Germany. FAU - Bickel, Horst AU - Bickel H AD - Department of Psychiatry and Psychotherapy, Technische Universitat Munchen, Germany. FAU - Sacco, Ralph L AU - Sacco RL AD - Department of Neurology, Miller School of Medicine, University of Miami, USA. FAU - Hofman, Albert AU - Hofman A AD - Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Mathiesen, Ellisiv B AU - Mathiesen EB AD - Department of Clinical Medicine, University of Tromso, Norway Department of Neurology, University Hospital of Northern Norway, Tromso, Norway. FAU - Gabriel, Rafael AU - Gabriel R AD - Instituto de Investigacion IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. FAU - Liu, Jing AU - Liu J AD - Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, China. FAU - Berenson, Gerald AU - Berenson G AD - Department of Medicine, Pediatrics, Biochemistry, Epidemiology, Tulane University School of Medicine and School of Public Health and Tropical Medicine, New Orleans, USA. FAU - Kavousi, Maryam AU - Kavousi M AD - Department of Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands. FAU - Price, Jackie F AU - Price JF AD - Centre for Population Health Sciences, University of Edinburgh, UK. LA - eng GR - MR/L003120/1/Medical Research Council/United Kingdom GR - RG/08/014/24067/British Heart Foundation/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Review PT - Research Support, Non-U.S. Gov't DEP - 20160108 PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 SB - IM MH - Atherosclerosis/diagnosis/*epidemiology MH - *Carotid Intima-Media Thickness MH - Disease Progression MH - Global Health MH - Humans MH - Incidence MH - Reference Values MH - Risk Factors OTO - NOTNLM OT - *Intima media thickness OT - *cardiovascular risk OT - *ethnicity OT - *geographic OT - *hazard ratio OT - *normal value EDAT- 2016/01/10 06:00 MHDA- 2017/12/27 06:00 CRDT- 2016/01/10 06:00 PHST- 2015/08/12 00:00 [received] PHST- 2015/12/15 00:00 [accepted] PHST- 2016/01/10 06:00 [entrez] PHST- 2016/01/10 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] AID - 2047487315625543 [pii] AID - 10.1177/2047487315625543 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2016 Jul;23(11):1165-73. doi: 10.1177/2047487315625543. Epub 2016 Jan 8. PMID- 27052543 OWN - NLM STAT- MEDLINE DCOM- 20170117 LR - 20170117 IS - 1365-2060 (Electronic) IS - 0785-3890 (Linking) VI - 48 IP - 4 DP - 2016 TI - Applicability of the 2013 ACC/AHA Risk Assessment and Cholesterol Treatment Guidelines in the real world: results from a multiethnic case-control study. PG - 282-92 LID - 10.3109/07853890.2016.1168934 [doi] AB - BACKGROUND: The 2013 ACC/AHA cholesterol treatment guidelines have introduced a new cardiovascular risk assessment approach (PCE) and have revisited the threshold for prescribing statins. This study aims to compare the ex ante application of the ACC/AHA and the ATP-III guideline models by using a multiethnic case-control study. METHODS: ATP-III-FRS and PCE were assessed in 739 patients with first STEMI and 739 age- and gender-matched controls; the proportion of cases and controls that would have been eligible for statin as primary prevention therapy and the discriminatory ability of both models were evaluated. RESULTS: The application of the ACC/AHA compared to the ATP-III model, resulted in an increase in sensitivity [94% (95%CI: 91%-95%) vs. 65% (61%-68%), p< 0.0001], a reduction in specificity [19% (15%-22%) vs. 55% (51%-59%), p< 0.0001] with similar global accuracy [0.56 (0.53-0.59) vs.0.59 (0.57-0.63), p ns]. When stratifying for ethnicity, the accuracy of the ACC/AHA model was higher in Europeans than in Chinese (p = 0.003) and to identified premature STEMI patients within Europeans much better compared to the ATP-III model (p = 0.0289). CONCLUSION: The application of the ACC/AHA model resulted in a significant reduction of first STEMI patients who would have escaped from preventive treatment. Age and ethnicity affected the accuracy of the ACC/AHA model improving the identification of premature STEMI among Europeans only. Key messages According to the ATP-III guideline model, about one-third of patients with STEMI would not be eligible for primary preventive treatment before STEMI. The application of the new ACC/AHA cholesterol treatment guideline model leads to a significant reduction of the percentage of patients with STEMI who would have been considered at lower risk before the STEMI. The global accuracy of the new ACC/AHA model is higher in the Europeans than in the Chinese and, moreover, among the Europeans, the application of the new ACC/AHA guideline model also improved identification of premature STEMI patients. FAU - Magnoni, Marco AU - Magnoni M AD - a IRCCS Ospedale San Raffaele and Universita Vita-Salute San Raffaele , Milan , Italy ; AD - b Heart Care Foundation Onlus , Florence , Italy ; FAU - Berteotti, Martina AU - Berteotti M AD - a IRCCS Ospedale San Raffaele and Universita Vita-Salute San Raffaele , Milan , Italy ; FAU - Norata, Giuseppe Danilo AU - Norata GD AD - c Department of Pharmacological and Biomolecular Sciences , Universita degli Studi di Milano , Milan , Italy. FAU - Limite, Luca Rosario AU - Limite LR AD - a IRCCS Ospedale San Raffaele and Universita Vita-Salute San Raffaele , Milan , Italy ; FAU - Peretto, Giovanni AU - Peretto G AD - a IRCCS Ospedale San Raffaele and Universita Vita-Salute San Raffaele , Milan , Italy ; FAU - Cristell, Nicole AU - Cristell N AD - a IRCCS Ospedale San Raffaele and Universita Vita-Salute San Raffaele , Milan , Italy ; FAU - Maseri, Attilio AU - Maseri A AD - b Heart Care Foundation Onlus , Florence , Italy ; FAU - Cianflone, Domenico AU - Cianflone D AD - a IRCCS Ospedale San Raffaele and Universita Vita-Salute San Raffaele , Milan , Italy ; LA - eng PT - Journal Article PT - Multicenter Study DEP - 20160407 PL - England TA - Ann Med JT - Annals of medicine JID - 8906388 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Aged MH - Cardiovascular Diseases/ethnology/*prevention & control MH - Case-Control Studies MH - Cholesterol/*blood MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use MH - Male MH - Middle Aged MH - Models, Theoretical MH - *Practice Guidelines as Topic MH - Primary Prevention/methods MH - Prospective Studies MH - Risk Assessment/methods MH - ST Elevation Myocardial Infarction/ethnology/prevention & control MH - Sensitivity and Specificity MH - United States OTO - NOTNLM OT - Risk assessment OT - myocardial infarction OT - primary prevention OT - statin EDAT- 2016/04/08 06:00 MHDA- 2017/01/18 06:00 CRDT- 2016/04/08 06:00 PHST- 2016/04/08 06:00 [entrez] PHST- 2016/04/08 06:00 [pubmed] PHST- 2017/01/18 06:00 [medline] AID - 10.3109/07853890.2016.1168934 [doi] PST - ppublish SO - Ann Med. 2016;48(4):282-92. doi: 10.3109/07853890.2016.1168934. Epub 2016 Apr 7. PMID- 26555147 OWN - NLM STAT- MEDLINE DCOM- 20160621 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 11 DP - 2015 TI - Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients. PG - e0142408 LID - 10.1371/journal.pone.0142408 [doi] AB - AIM: The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. MATERIALS & METHODS: Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. RESULTS: The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71 +/- 0.28 vs 1.11+/-0.69 mug/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76 +/- 0.16 vs 0.94 +/- 0.49 mug/mL per mg/Kg for EPHX1 c.337 CC vs TT; P<0.05 for both). Carriers of the EPHX1 c.416A>G showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13 +/- 0.08 to 0.26 +/- 0.17, p<0.05) also of CBZD to CBZE (1.74 +/- 1.06 to 3.08 +/- 2.90; P<0.05) and CDRCBZD (0.13 +/- 0.08 vs 0.24 +/- 0.19 mug/mL per mg/Kg; P<0.05). ABCB1 3455C>T SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657 +/- 285 vs 489 +/- 231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84 +/- 4.37 vs 7.41 +/- 3.43 mug/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. CONCLUSIONS: The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy. FAU - Daci, Armond AU - Daci A AD - Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. AD - Institute of Pharmacology and Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Beretta, Giangiacomo AU - Beretta G AD - Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Vllasaliu, Driton AU - Vllasaliu D AD - University of Lincoln, School of Pharmacy, Joseph Banks Laboratories, Green Lane, Lincoln, LN6 7DL, United Kingdom. FAU - Shala, Aida AU - Shala A AD - Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. FAU - Govori, Valbona AU - Govori V AD - Neurology Clinic, University Clinical Center of Kosova, Prishtina, Kosovo. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. AD - Center for the Study of Atherosclerosis, Ospedale Bassini, Cinisello Balsamo, Italy. FAU - Krasniqi, Shaip AU - Krasniqi S AD - Institute of Pharmacology and Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151110 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anticonvulsants) RN - 0 (NAV1.1 Voltage-Gated Sodium Channel) RN - 0 (SCN1A protein, human) RN - 33CM23913M (Carbamazepine) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - EC 3.3.2.9 (EPHX1 protein, human) SB - IM MH - Adolescent MH - Adult MH - Albania MH - Anticonvulsants/*blood/pharmacokinetics/therapeutic use MH - Carbamazepine/*blood/pharmacokinetics/therapeutic use MH - Chromatography, High Pressure Liquid MH - Epilepsy/*drug therapy MH - Epoxide Hydrolases/*genetics MH - Ethnic Groups/*genetics MH - Female MH - Humans MH - Male MH - Middle Aged MH - NAV1.1 Voltage-Gated Sodium Channel/*genetics MH - *Polymorphism, Single Nucleotide MH - Spectrophotometry, Ultraviolet MH - Young Adult PMC - PMC4640545 EDAT- 2015/11/12 06:00 MHDA- 2016/06/22 06:00 CRDT- 2015/11/12 06:00 PHST- 2015/06/05 00:00 [received] PHST- 2015/10/20 00:00 [accepted] PHST- 2015/11/12 06:00 [entrez] PHST- 2015/11/12 06:00 [pubmed] PHST- 2016/06/22 06:00 [medline] AID - 10.1371/journal.pone.0142408 [doi] AID - PONE-D-15-24598 [pii] PST - epublish SO - PLoS One. 2015 Nov 10;10(11):e0142408. doi: 10.1371/journal.pone.0142408. eCollection 2015. PMID- 26377896 OWN - NLM STAT- MEDLINE DCOM- 20160104 LR - 20150917 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 43 IP - 3 DP - 2015 Sep 15 TI - The Cellular and Molecular Basis of Translational Immunometabolism. PG - 421-34 LID - 10.1016/j.immuni.2015.08.023 [doi] LID - S1074-7613(15)00356-8 [pii] AB - The immune response requires major changes to metabolic processes, and indeed, energy metabolism and functional activation are fully integrated in immune cells to determine their ability to divide, differentiate, and carry out effector functions. Immune cell metabolism has therefore become an attractive target area for therapeutic purposes. A neglected aspect in the translation of immunometabolism is the critical connection between systemic and cellular metabolism. Here, we discuss the importance of understanding and manipulating the integration of systemic and immune cell metabolism through in-depth analysis of immune cell phenotype and function in human metabolic diseases and, in parallel, of the effects of conventional metabolic drugs on immune cell differentiation and function. We examine how the recent identification of selective metabolic programs operating in distinct immune cell subsets and functions has the potential to deliver tools for cell- and function-specific immunometabolic targeting. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy; Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, 20092 Milan, Italy. Electronic address: danilo.norata@unimi.it. FAU - Caligiuri, Giuseppina AU - Caligiuri G AD - Unite 1148, INSERM, Hopital X Bichat, 75018 Paris, France; Universite Paris Diderot, Sorbonne Paris Cite, 75013 Paris, France; Departement Hospitalo-Universitaire "FIRE," 75018 Paris, France. FAU - Chavakis, Triantafyllos AU - Chavakis T AD - Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Technische Universitat Dresden, 01307 Dresden, Germany. FAU - Matarese, Giuseppe AU - Matarese G AD - Dipartimento di Medicina e Chirurgia, Universita degli Studi di Salerno, Baronissi, 84081 Salerno, Italy; IRCCS MultiMedica, 20138 Milan, Italy. FAU - Netea, Mihai Gheorge AU - Netea MG AD - Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands. FAU - Nicoletti, Antonino AU - Nicoletti A AD - Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Technische Universitat Dresden, 01307 Dresden, Germany. FAU - O'Neill, Luke A J AU - O'Neill LA AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. FAU - Marelli-Berg, Federica M AU - Marelli-Berg FM AD - William Harvey Research Institute, Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. LA - eng GR - RG/14/2/30616/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Immunity JT - Immunity JID - 9432918 SB - IM MH - Animals MH - Energy Metabolism/genetics/*immunology MH - Humans MH - Immune System/cytology/*immunology/*metabolism MH - Macrophages/immunology/metabolism MH - Metabolic Diseases/genetics/immunology/metabolism MH - Metabolic Networks and Pathways/genetics/*immunology MH - Models, Immunological MH - T-Lymphocyte Subsets/immunology/metabolism EDAT- 2015/09/18 06:00 MHDA- 2016/01/05 06:00 CRDT- 2015/09/18 06:00 PHST- 2015/07/06 00:00 [received] PHST- 2015/09/18 06:00 [entrez] PHST- 2015/09/18 06:00 [pubmed] PHST- 2016/01/05 06:00 [medline] AID - S1074-7613(15)00356-8 [pii] AID - 10.1016/j.immuni.2015.08.023 [doi] PST - ppublish SO - Immunity. 2015 Sep 15;43(3):421-34. doi: 10.1016/j.immuni.2015.08.023. PMID- 25770018 OWN - NLM STAT- MEDLINE DCOM- 20160411 LR - 20181113 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 220 IP - 8 DP - 2015 Aug TI - Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichment. PG - 1025-9 LID - 10.1016/j.imbio.2015.02.006 [doi] LID - S0171-2985(15)00033-9 [pii] AB - Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation. CI - Copyright (c) 2015 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Garetto, Stefano AU - Garetto S AD - Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy. FAU - Trovato, Anna Elisa AU - Trovato AE AD - Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy. FAU - Lleo, Ana AU - Lleo A AD - Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy; Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universita degli Studi di Milano, Via Manzoni 56, Rozzano (Milan), Italy. FAU - Sala, Federica AU - Sala F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Martini, Elisa AU - Martini E AD - Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy. FAU - Betz, Alexander G AU - Betz AG AD - Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, 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 - Invernizzi, Pietro AU - Invernizzi P AD - Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy; Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA. FAU - Kallikourdis, Marinos AU - Kallikourdis M AD - Adaptive Immunity Laboratory, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano (Milano), Italy; Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universita degli Studi di Milano, Via Manzoni 56, Rozzano (Milan), Italy. Electronic address: marinos.kallikourdis@humanitasresearch.it. LA - eng GR - 18297/Arthritis Research UK/United Kingdom GR - GGP13002/Telethon/Italy GR - Arthritis Research UK/United Kingdom GR - Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150226 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Receptors, LDL) SB - IM MH - Animals MH - Arthritis/*immunology MH - Atherosclerosis/*immunology MH - Autoimmune Diseases/*immunology MH - Cell Proliferation MH - Diet, Atherogenic/adverse effects MH - Disease Models, Animal MH - Disease Progression MH - Female MH - Humans MH - Inflammation/*immunology MH - Liver Cirrhosis, Biliary/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Receptors, LDL/genetics MH - T-Lymphocytes, Regulatory/*immunology PMC - PMC4457006 OTO - NOTNLM OT - Atherosclerosis OT - Autoimmunity OT - Inflammation OT - Primary biliary cirrhosis OT - Regulatory T cells OT - Rheumatoid arthritis EDAT- 2015/03/15 06:00 MHDA- 2016/04/12 06:00 CRDT- 2015/03/15 06:00 PHST- 2014/10/01 00:00 [received] PHST- 2015/02/03 00:00 [revised] PHST- 2015/02/19 00:00 [accepted] PHST- 2015/03/15 06:00 [entrez] PHST- 2015/03/15 06:00 [pubmed] PHST- 2016/04/12 06:00 [medline] AID - S0171-2985(15)00033-9 [pii] AID - 10.1016/j.imbio.2015.02.006 [doi] PST - ppublish SO - Immunobiology. 2015 Aug;220(8):1025-9. doi: 10.1016/j.imbio.2015.02.006. Epub 2015 Feb 26. PMID- 26100075 OWN - NLM STAT- MEDLINE DCOM- 20160405 LR - 20181113 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 6 DP - 2015 Jun 23 TI - PI3K-C2gamma is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling. PG - 7400 LID - 10.1038/ncomms8400 [doi] AB - In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective interplays exist is currently unclear. Here we report that insulin signalling triggers the association of the liver-specific class II PI3K isoform gamma (PI3K-C2gamma) with Rab5-GTP, and its recruitment to Rab5-positive early endosomes. In these vesicles, PI3K-C2gamma produces a phosphatidylinositol-3,4-bisphosphate pool specifically required for delayed and sustained endosomal Akt2 stimulation. Accordingly, loss of PI3K-C2gamma does not affect insulin-dependent Akt1 activation as well as S6K and FoxO1-3 phosphorylation, but selectively reduces Akt2 activation, which specifically inhibits glycogen synthase activity. As a consequence, PI3K-C2gamma-deficient mice display severely reduced liver accumulation of glycogen and develop hyperlipidemia, adiposity as well as insulin resistance with age or after consumption of a high-fat diet. Our data indicate PI3K-C2gamma supports an isoenzyme-specific forking of insulin-mediated signal transduction to an endosomal pool of Akt2, required for glucose homeostasis. FAU - Braccini, Laura AU - Braccini L AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Ciraolo, Elisa AU - Ciraolo E AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Campa, Carlo C AU - Campa CC AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Perino, Alessia AU - Perino A AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Longo, Dario L AU - Longo DL AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Tibolla, Gianpaolo AU - Tibolla G AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy. FAU - Pregnolato, Marco AU - Pregnolato M AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Cao, Yanyan AU - Cao Y AD - Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, New York 10461, USA. FAU - Tassone, Beatrice AU - Tassone B AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Damilano, Federico AU - Damilano F AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Laffargue, Muriel AU - Laffargue M AD - INSERM UMR 1048, I2MC, Bat. L3, 1 av Jean-Poulhes, BP 84225, Toulouse 4 31432, France. FAU - Calautti, Enzo AU - Calautti E AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. FAU - Falasca, Marco AU - Falasca M AD - Metabolic Signalling Group, School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth, Western Australia 6102, Australia. FAU - Norata, Giuseppe D AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan 20133, Italy. FAU - Backer, Jonathan M AU - Backer JM AD - Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, New York 10461, USA. FAU - Hirsch, Emilio AU - Hirsch E AUID- ORCID: 0000000290736024 AD - Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy. LA - eng GR - R01 AG039632/AG/NIA NIH HHS/United States GR - GM112524/GM/NIGMS NIH HHS/United States GR - P30 DK041296/DK/NIDDK NIH HHS/United States GR - GGP13002/Telethon/Italy GR - R01 GM112524/GM/NIGMS NIH HHS/United States GR - TCP06001/Telethon/Italy GR - AG039632/AG/NIA NIH HHS/United States GR - P30 DK020541/DK/NIDDK NIH HHS/United States GR - T32 HL007374/HL/NHLBI NIH HHS/United States GR - P60 DK020541/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150623 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Forkhead Transcription Factors) RN - 0 (Insulin) RN - 0 (Phosphatidylinositol Phosphates) RN - 0 (phosphatidylinositol 3,4-diphosphate) RN - 9005-79-2 (Glycogen) RN - EC 2.4.1.11 (Glycogen Synthase) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (Pik3c2g protein, mouse) RN - EC 2.7.11.1 (Akt1 protein, mouse) RN - EC 2.7.11.1 (Akt2 protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 3.6.5.2 (rab5 GTP-Binding Proteins) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adiposity/genetics MH - Aging/*genetics MH - Animals MH - Diet, High-Fat MH - Endosomes/metabolism MH - Forkhead Transcription Factors/metabolism MH - Glucose/metabolism MH - Glycogen/*metabolism MH - Glycogen Synthase/metabolism MH - Hepatocytes/*metabolism MH - Homeostasis MH - Hyperlipidemias/genetics MH - Insulin/*metabolism MH - Insulin Resistance/genetics MH - Liver/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Phosphatidylinositol 3-Kinases/*genetics/metabolism MH - Phosphatidylinositol Phosphates/metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction MH - rab5 GTP-Binding Proteins/*metabolism PMC - PMC4479417 MID - NIHMS688538 EDAT- 2015/06/24 06:00 MHDA- 2016/04/06 06:00 CRDT- 2015/06/24 06:00 PHST- 2014/10/10 00:00 [received] PHST- 2015/05/06 00:00 [accepted] PHST- 2015/06/24 06:00 [entrez] PHST- 2015/06/24 06:00 [pubmed] PHST- 2016/04/06 06:00 [medline] AID - ncomms8400 [pii] AID - 10.1038/ncomms8400 [doi] PST - epublish SO - Nat Commun. 2015 Jun 23;6:7400. doi: 10.1038/ncomms8400. PMID- 25522998 OWN - NLM STAT- MEDLINE DCOM- 20150415 LR - 20151119 IS - 0171-2004 (Print) IS - 0171-2004 (Linking) VI - 224 DP - 2015 TI - Impact of systemic inflammation and autoimmune diseases on apoA-I and HDL plasma levels and functions. PG - 455-82 LID - 10.1007/978-3-319-09665-0_14 [doi] AB - The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk. In this narrative review, we will focus on the pathophysiological relevance of HDL and apoA-I levels/functions in different acute and chronic inflammatory pathophysiological conditions. FAU - Montecucco, Fabrizio AU - Montecucco F AD - Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 rue Gabrielle Perret-Gentil, 1211, Geneva, Switzerland. FAU - Favari, Elda AU - Favari E FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Ronda, Nicoletta AU - Ronda N FAU - Nofer, Jerzy-Roch AU - Nofer JR FAU - Vuilleumier, Nicolas AU - Vuilleumier N LA - eng PT - Journal Article PT - Review PL - Germany TA - Handb Exp Pharmacol JT - Handbook of experimental pharmacology JID - 7902231 RN - 0 (APOA1 protein, human) RN - 0 (Apolipoprotein A-I) RN - 0 (Biomarkers) RN - 0 (Lipoproteins, HDL) RN - 0 (Lysophospholipids) RN - 0 (Receptors, Lysosphingolipid) RN - 26993-30-6 (sphingosine 1-phosphate) RN - NGZ37HRE42 (Sphingosine) SB - IM MH - Animals MH - Apolipoprotein A-I/*blood/chemistry MH - Autoimmune Diseases/*blood/immunology MH - Biomarkers/blood MH - Humans MH - Immunity, Innate MH - Inflammation/*blood/immunology MH - Lipoproteins, HDL/*blood/chemistry MH - Lymphocytes/immunology/metabolism MH - Lysophospholipids/blood MH - Membrane Microdomains/immunology/metabolism MH - Protein Conformation MH - Receptors, Lysosphingolipid/blood MH - Sphingosine/analogs & derivatives/blood MH - Structure-Activity Relationship 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_14 [doi] PST - ppublish SO - Handb Exp Pharmacol. 2015;224:455-82. doi: 10.1007/978-3-319-09665-0_14. PMID- 25960621 OWN - NLM STAT- MEDLINE DCOM- 20160201 LR - 20181113 IS - 1466-1861 (Electronic) IS - 0962-9351 (Linking) VI - 2015 DP - 2015 TI - Markers of inflammation associated with plaque progression and instability in patients with carotid atherosclerosis. PG - 718329 LID - 10.1155/2015/718329 [doi] AB - Atherosclerosis is the focal expression of a systemic disease affecting medium- and large-sized arteries, in which traditional cardiovascular risk factor and immune factors play a key role. It is well accepted that circulating biomarkers, including C-reactive protein and interleukin-6, reliably predict major cardiovascular events, including myocardial infarction or death. However, the relevance of biomarkers of systemic inflammation to atherosclerosis progression in the carotid artery is less established. The large majority of clinical studies focused on the association between biomarkers and subclinical atherosclerosis, that is, carotid intima-media thickening (cIMT), which represents an earlier stage of the disease. The aim of this work is to review inflammatory biomarkers that were associated with a higher atherosclerotic burden, a faster disease progression, and features of plaque instability, such as inflammation or neovascularization, in patients with carotid atherosclerotic plaque, which represents an advanced stage of disease compared with cIMT. The association of biomarkers with the occurrence of cerebrovascular events, secondary to carotid plaque rupture, will also be presented. Currently, the degree of carotid artery stenosis is used to predict the risk of future cerebrovascular events in patients affected by carotid atherosclerosis. However, this strategy appears suboptimal. The identification of suitable biomarkers could provide a useful adjunctive criterion to ensure better risk stratification and optimize management. FAU - Ammirati, Enrico AU - Ammirati E AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 58-60, 20132 Milan, Italy ; Cardiovascular and Thoracic Department, Niguarda Ca' Granda Hospital, Milan, Italy. FAU - Moroni, Francesco AU - Moroni F AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 58-60, 20132 Milan, Italy. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Departement of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy ; Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy ; Blizard Institute, Queen Mary University, London, UK. FAU - Magnoni, Marco AU - Magnoni M AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 58-60, 20132 Milan, Italy. FAU - Camici, Paolo G AU - Camici PG AD - Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 58-60, 20132 Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150416 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Biomarkers) RN - 0 (Interleukin-6) RN - 0 (Lipids) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Biomarkers/blood MH - C-Reactive Protein/metabolism MH - Cardiovascular Diseases/blood MH - Carotid Arteries/metabolism MH - Carotid Artery Diseases/*metabolism MH - Carotid Intima-Media Thickness MH - Disease Progression MH - Humans MH - Immune System MH - Inflammation/*metabolism MH - Interleukin-6/blood MH - Lipids/blood MH - Neovascularization, Pathologic MH - Plaque, Atherosclerotic/metabolism MH - Risk Factors PMC - PMC4415469 EDAT- 2015/05/12 06:00 MHDA- 2016/02/02 06:00 CRDT- 2015/05/12 06:00 PHST- 2015/02/23 00:00 [received] PHST- 2015/03/22 00:00 [accepted] PHST- 2015/05/12 06:00 [entrez] PHST- 2015/05/12 06:00 [pubmed] PHST- 2016/02/02 06:00 [medline] AID - 10.1155/2015/718329 [doi] PST - ppublish SO - Mediators Inflamm. 2015;2015:718329. doi: 10.1155/2015/718329. Epub 2015 Apr 16. PMID- 24681137 OWN - NLM STAT- MEDLINE DCOM- 20140811 LR - 20181202 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 63 IP - 24 DP - 2014 Jun 24 TI - The missing link between high-density lipoprotein cholesterol and inflammatory response in cardiovascular disease. PG - 2747-8 LID - 10.1016/j.jacc.2013.12.057 [doi] LID - S0735-1097(14)01517-4 [pii] FAU - Ammirati, Enrico AU - Ammirati E FAU - Scotti, Isabella AU - Scotti I FAU - Norata, Giuseppe D AU - Norata GD LA - eng PT - Letter PT - Comment DEP - 20140326 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Cholesterol, HDL) SB - AIM SB - IM CON - J Am Coll Cardiol. 2013 Nov 12;62(20):1826-33. PMID: 23973693 MH - Cholesterol, HDL/*blood MH - Female MH - Humans MH - Male MH - Myocardial Ischemia/*blood/*mortality EDAT- 2014/04/01 06:00 MHDA- 2014/08/12 06:00 CRDT- 2014/04/01 06:00 PHST- 2013/12/03 00:00 [received] PHST- 2013/12/17 00:00 [accepted] PHST- 2014/04/01 06:00 [entrez] PHST- 2014/04/01 06:00 [pubmed] PHST- 2014/08/12 06:00 [medline] AID - S0735-1097(14)01517-4 [pii] AID - 10.1016/j.jacc.2013.12.057 [doi] PST - ppublish SO - J Am Coll Cardiol. 2014 Jun 24;63(24):2747-8. doi: 10.1016/j.jacc.2013.12.057. Epub 2014 Mar 26. PMID- 24854692 OWN - NLM STAT- MEDLINE DCOM- 20150219 LR - 20161125 IS - 1873-2933 (Electronic) IS - 0009-9120 (Linking) VI - 47 IP - 9 DP - 2014 Jun TI - New therapeutic principles for Familial Hypercholesterolemia. PG - 756 LID - 10.1016/j.clinbiochem.2014.05.046 [doi] LID - S0009-9120(14)00274-4 [pii] FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro per lo Studio dell'Aterosclerosi, Societa Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy. Electronic address: danilo.norata@unimi.it. LA - eng PT - Journal Article DEP - 20140520 PL - United States TA - Clin Biochem JT - Clinical biochemistry JID - 0133660 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 - Anticholesteremic Agents/pharmacology/therapeutic use MH - Child MH - Early Diagnosis MH - Humans MH - Hypercholesterolemia/genetics/*therapy MH - Molecular Targeted Therapy MH - Proprotein Convertase 9 MH - Proprotein Convertases/antagonists & inhibitors MH - Serine Endopeptidases EDAT- 2014/05/24 06:00 MHDA- 2015/02/20 06:00 CRDT- 2014/05/24 06:00 PHST- 2014/05/24 06:00 [entrez] PHST- 2014/05/24 06:00 [pubmed] PHST- 2015/02/20 06:00 [medline] AID - S0009-9120(14)00274-4 [pii] AID - 10.1016/j.clinbiochem.2014.05.046 [doi] PST - ppublish SO - Clin Biochem. 2014 Jun;47(9):756. doi: 10.1016/j.clinbiochem.2014.05.046. Epub 2014 May 20. PMID- 25002170 OWN - NLM STAT- MEDLINE DCOM- 20140829 LR - 20161125 IS - 1827-6806 (Print) IS - 1827-6806 (Linking) VI - 15 IP - 5 DP - 2014 May TI - [PCSK9 inhibitors and dyslipidemias: an update on clinical evidence]. PG - 301-5 LID - 10.1714/1563.17029 [doi] AB - Elevated plasma LDL cholesterol (LDL-C) levels are associated with cardiovascular diseases and statin therapy was proven to decrease LDL-C and reduce cardiovascular death. However, in patients at high cardiovascular risk, achievement of optimal LDL-C levels is challenging, and therefore additional strategies for further loweing LDL-C levels are under development. Recently, silencing of apolipoprotein B gene and MTP inhibition have been approved for the treatment of patients with familial hypercholesterolemia, and there is great interest in the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9). PCSK9 promotes the degradation of the LDL receptor. The inhibition of PCSK9 favors LDL catabolism and reduces plasma LDLC levels. Monoclonal antibodies against PCSK9 represent so far the most advanced approach in clinical development, with alirocumab, evolocumab and bococizumab under advanced clinical development. Recent data from the first phase III studies show LDL-C reduction in monotherapy and on top of statins. Long-term studies on cardiovascular endpoints are ongoing and the results will be crucial to translate the benefit of this promising approach into clinical practice. FAU - Norata, Giuseppe Danilo AU - Norata GD LA - ita PT - Journal Article PT - Review TT - Inibitori di PCSK9 e dislipidemie: le evidenze cliniche. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Biomarkers) RN - 0 (Cholesterol, LDL) RN - 0 (Hypolipidemic 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 - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Biomarkers/blood MH - Cholesterol, LDL/*blood/drug effects MH - Clinical Trials as Topic MH - Dyslipidemias/*drug therapy/metabolism MH - Evidence-Based Medicine MH - Humans MH - Hypolipidemic Agents/*therapeutic use MH - Proprotein Convertase 9 MH - Proprotein Convertases/*antagonists & inhibitors MH - Serine Endopeptidases MH - Treatment Outcome EDAT- 2014/07/09 06:00 MHDA- 2014/08/30 06:00 CRDT- 2014/07/09 06:00 PHST- 2014/07/09 06:00 [entrez] PHST- 2014/07/09 06:00 [pubmed] PHST- 2014/08/30 06:00 [medline] AID - 10.1714/1563.17029 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2014 May;15(5):301-5. doi: 10.1714/1563.17029. PMID- 24324578 OWN - NLM STAT- MEDLINE DCOM- 20140908 LR - 20181202 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 12 DP - 2013 TI - The thyroid receptor modulator KB3495 reduces atherosclerosis independently of total cholesterol in the circulation in ApoE deficient mice. PG - e78534 LID - 10.1371/journal.pone.0078534 [doi] AB - BACKGROUND: Thyroid hormones (TH) regulate cholesterol metabolism but their use as lipid-lowering drugs is restricted due to negative cardiac effects. TH mimetic compounds modulating TH receptor beta (THRbeta) have been designed as potential drugs, reducing serum cholesterol levels while avoiding apparent deleterious cardiac effects. OBJECTIVE: Using ApoE deficient mice, we examined whether KB3495, a TH mimetic compound, reduces atherosclerosis and if there is a synergistic effect with atorvastatin. The effect of KB3495 was investigated after 10 and 25 weeks. RESULTS: KB3495 treatment reduced atherosclerotic plaque formation in aorta and decreased the cholesteryl ester (CE) content by 57%. Treatment with KB3495 was also associated with a reduction of macrophage content in the atherosclerotic plaques and reduced serum levels of IL-1beta, TNFalpha, IL-6, Interferon gamma, MCP-1 and M-CSF. Serum lipoprotein analysis showed no change in total cholesterol levels in ApoB-containing lipoproteins. KB3495 alone increased fecal BA excretion by 90%. The excretion of neutral sterols increased in all groups, with the largest increase in the combination group (350%). After 25 weeks, the animals treated with KB3495 showed 50% lower CE levels in the skin and even further reductions were observed in the combination group where the CE levels were reduced by almost 95% as compared to controls. CONCLUSION: KB3495 treatment reduced atherosclerosis independently of total cholesterol levels in ApoB-containing lipoproteins likely by stimulation of sterol excretion from the body and by inhibition of the inflammatory response. FAU - Mork, Lisa-Mari AU - Mork LM AD - Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. FAU - Rehnmark, Stefan AU - Rehnmark S FAU - Davoodpour, Padideh AU - Davoodpour P FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Larsson, Lilian AU - Larsson L FAU - Witt, Michael-Robin AU - Witt MR FAU - Malm, Johan AU - Malm J FAU - Parini, Paolo AU - Parini P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131204 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anticholesteremic Agents) RN - 0 (Apolipoproteins B) RN - 0 (Apolipoproteins E) RN - 0 (Bile Acids and Salts) RN - 0 (Cytokines) RN - 0 (Heptanoic Acids) RN - 0 (Pyrroles) RN - 0 (Thyroid Hormones) RN - A0JWA85V8F (Atorvastatin) SB - IM MH - Animals MH - Anticholesteremic Agents/chemical synthesis/*pharmacology MH - Apolipoproteins B/metabolism MH - Apolipoproteins E/deficiency/genetics MH - Atherosclerosis/*drug therapy/metabolism/pathology MH - Atorvastatin MH - Bile Acids and Salts/metabolism MH - Biological Transport/drug effects MH - Cytokines/biosynthesis/metabolism MH - Disease Models, Animal MH - Drug Synergism MH - Feces/chemistry MH - Heptanoic Acids/*pharmacology MH - Male MH - Mice MH - Mice, Knockout MH - Molecular Mimicry MH - Plaque, Atherosclerotic/metabolism/pathology/*prevention & control MH - Pyrroles/*pharmacology MH - Thyroid Hormones/chemistry PMC - PMC3850901 EDAT- 2013/12/11 06:00 MHDA- 2014/09/10 06:00 CRDT- 2013/12/11 06:00 PHST- 2013/03/21 00:00 [received] PHST- 2013/09/20 00:00 [accepted] PHST- 2013/12/11 06:00 [entrez] PHST- 2013/12/11 06:00 [pubmed] PHST- 2014/09/10 06:00 [medline] AID - 10.1371/journal.pone.0078534 [doi] AID - PONE-D-13-11668 [pii] PST - epublish SO - PLoS One. 2013 Dec 4;8(12):e78534. doi: 10.1371/journal.pone.0078534. eCollection 2013. PMID- 24005140 OWN - NLM STAT- MEDLINE DCOM- 20140116 LR - 20141120 IS - 0392-0488 (Print) IS - 0392-0488 (Linking) VI - 148 IP - 5 DP - 2013 Oct TI - The zebrafish embryo derivative affects cell viability of epidermal cells: a possible role in the treatment of psoriasis. PG - 479-83 AB - In patients affected by psoriasis, use of a topical formula containing a derivative of zebrafish embryos was associated with reduced skin inflammation and dermal turnover, as well as a generally better outcome. In an attempt to understand the molecular mechanisms lying beyond these findings, we investigated the anti-proliferative effects of the zebrafish embryos derivative by addressing the mitochondrial function (MTT assay) and cell nuclei distribution (Hoestch staining). In cell cultures stimulated with fetal calf serum (FCS) or epidermal growth factor (EGF), the zebrafish derivative significantly inhibited cell proliferation induced by either approach, although the effect was stronger in cells stimulated with FCS. These results suggest that the zebrafish embryos derivative may dampen increased cell proliferation; this observation may be relevant to cutaneous pathologies related to altered proliferative mechanisms, including psoriasis. FAU - Norata, G D AU - Norata GD AD - Department of Biomolecular Sciences, University of Milan, Milan, Italy - danilo.norata@unimi.it. FAU - Biava, P M AU - Biava PM FAU - Di Pierro, F AU - Di Pierro F LA - eng PT - Journal Article PL - Italy TA - G Ital Dermatol Venereol JT - Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia JID - 8102852 RN - 0 (Culture Media) RN - 0 (Tissue Extracts) RN - 62229-50-9 (Epidermal Growth Factor) SB - IM MH - Animals MH - Cattle MH - Cell Nucleus/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured/drug effects MH - Culture Media/pharmacology MH - Drug Evaluation, Preclinical MH - Epidermal Growth Factor/pharmacology MH - Fetal Blood MH - Humans MH - In Vitro Techniques MH - Keratinocytes/*drug effects/ultrastructure MH - Mitochondria/drug effects MH - Psoriasis/*drug therapy MH - Tissue Extracts/*pharmacology MH - Zebrafish/*embryology EDAT- 2013/09/06 06:00 MHDA- 2014/01/17 06:00 CRDT- 2013/09/06 06:00 PHST- 2013/09/06 06:00 [entrez] PHST- 2013/09/06 06:00 [pubmed] PHST- 2014/01/17 06:00 [medline] AID - R23Y2013N05A0479 [pii] PST - ppublish SO - G Ital Dermatol Venereol. 2013 Oct;148(5):479-83. PMID- 23539170 OWN - NLM STAT- MEDLINE DCOM- 20131030 LR - 20151119 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 13 IP - 2 DP - 2013 Apr TI - Pharmacogenetics in cardiovascular disorders: an update on the principal drugs. PG - 79-85 LID - 10.1007/s40256-013-0020-9 [doi] AB - In the coming years, genomics will impact clinical practice in multiple ways. However, one of the most important applications will be in the determination of the best treatments in personalized medicine. This is, in fact, one of the fields in which genetic variants have already been most successful and useful to clinicians. Here, we briefly review the current state of the art on pharmacogenomics and its applications to modern cardiovascular medicine. FAU - Predazzi, Irene M AU - Predazzi IM AD - Center for Human Genetics research, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, 511 Light Hall, 2215 Garland Avenue, Nashville, TN 37232, USA. Irene.m.predazzi@vanderbilt.edu FAU - Mango, Ruggiero AU - Mango R FAU - Norata, Giuseppe D AU - Norata GD FAU - Di Daniele, Nicola AU - Di Daniele N FAU - Sergi, Domenico AU - Sergi D FAU - Romeo, Francesco AU - Romeo F FAU - Novelli, Giuseppe AU - Novelli G LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Platelet Aggregation Inhibitors) RN - 5Q7ZVV76EI (Warfarin) SB - IM MH - Cardiovascular Diseases/drug therapy/*genetics MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/pharmacokinetics/*therapeutic use MH - Pharmacogenetics/*methods MH - Platelet Aggregation Inhibitors/adverse effects/pharmacokinetics/*therapeutic use MH - Precision Medicine/*methods MH - Warfarin/adverse effects/pharmacokinetics/*therapeutic use EDAT- 2013/03/30 06:00 MHDA- 2013/10/31 06:00 CRDT- 2013/03/30 06:00 PHST- 2013/03/30 06:00 [entrez] PHST- 2013/03/30 06:00 [pubmed] PHST- 2013/10/31 06:00 [medline] AID - 10.1007/s40256-013-0020-9 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2013 Apr;13(2):79-85. doi: 10.1007/s40256-013-0020-9. PMID- 23261173 OWN - NLM STAT- MEDLINE DCOM- 20130718 LR - 20181202 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 226 IP - 2 DP - 2013 Feb TI - European lipoprotein club: report of the 35th ELC annual conference (Tutzing, 10th-13th September 2012). PG - 510-6 LID - 10.1016/j.atherosclerosis.2012.11.030 [doi] LID - S0021-9150(12)00825-8 [pii] FAU - Costet, Philippe AU - Costet P AD - INSERM U915, IRTUN, 8 quai Moncousu BP70721, F-44007 Nantes, France. FAU - Ehrenborg, Ewa AU - Ehrenborg E FAU - Fisher, Rachel AU - Fisher R FAU - Fielding, Barbara AU - Fielding B FAU - Groen, Albert AU - Groen A FAU - Kardassis, Dimitris AU - Kardassis D FAU - Malle, Ernst AU - Malle E FAU - Mulder, Monique AU - Mulder M FAU - Niemeier, Andreas AU - Niemeier A FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Hansen, Anne Tybjaerg AU - Hansen AT FAU - Eckardstein, Arnold von AU - Eckardstein Av LA - eng PT - Congress PT - Research Support, Non-U.S. Gov't DEP - 20121205 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (ANGPTL4 protein, human) RN - 0 (Angiopoietin-like 4 Protein) RN - 0 (Angiopoietins) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, HDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Angiopoietin-like 4 Protein MH - Angiopoietins/physiology MH - Animals MH - Cholesterol/metabolism MH - Diabetes Mellitus, Type 2/physiopathology MH - Energy Metabolism MH - Humans MH - Inflammation/physiopathology MH - Lipid Metabolism Disorders/physiopathology MH - Lipoproteins/*metabolism MH - Lipoproteins, HDL/metabolism EDAT- 2012/12/25 06:00 MHDA- 2013/07/19 06:00 CRDT- 2012/12/25 06:00 PHST- 2012/11/26 00:00 [received] PHST- 2012/11/28 00:00 [accepted] PHST- 2012/12/25 06:00 [entrez] PHST- 2012/12/25 06:00 [pubmed] PHST- 2013/07/19 06:00 [medline] AID - S0021-9150(12)00825-8 [pii] AID - 10.1016/j.atherosclerosis.2012.11.030 [doi] PST - ppublish SO - Atherosclerosis. 2013 Feb;226(2):510-6. doi: 10.1016/j.atherosclerosis.2012.11.030. Epub 2012 Dec 5. PMID- 22773429 OWN - NLM STAT- MEDLINE DCOM- 20120917 LR - 20181201 IS - 1524-4571 (Electronic) IS - 0009-7330 (Linking) VI - 111 IP - 2 DP - 2012 Jul 6 TI - Antigen-dependent and antigen-independent pathways modulate CD4+CD28null T-cells during atherosclerosis. PG - e48-9; author reply e50-1 LID - 10.1161/CIRCRESAHA.112.271627 [doi] FAU - Ammirati, Enrico AU - Ammirati E FAU - Monaco, Claudia AU - Monaco C FAU - Norata, Giuseppe Danilo AU - Norata GD LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't PT - Comment PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Receptors, OX40) RN - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9) SB - IM CON - Circ Res. 2012 Mar 16;110(6):857-69. PMID: 22282196 MH - Acute Coronary Syndrome/*immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - Female MH - Humans MH - Male MH - Receptors, OX40/*immunology MH - Signal Transduction/*immunology MH - Tumor Necrosis Factor Receptor Superfamily, Member 9/*immunology EDAT- 2012/07/10 06:00 MHDA- 2012/09/18 06:00 CRDT- 2012/07/10 06:00 PHST- 2012/07/10 06:00 [entrez] PHST- 2012/07/10 06:00 [pubmed] PHST- 2012/09/18 06:00 [medline] AID - 111/2/e48 [pii] AID - 10.1161/CIRCRESAHA.112.271627 [doi] PST - ppublish SO - Circ Res. 2012 Jul 6;111(2):e48-9; author reply e50-1. doi: 10.1161/CIRCRESAHA.112.271627. PMID- 22415012 OWN - NLM STAT- MEDLINE DCOM- 20121119 LR - 20181113 IS - 1528-3658 (Electronic) IS - 1076-1551 (Linking) VI - 18 DP - 2012 May 9 TI - A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis. PG - 712-8 LID - 10.2119/molmed.2012.00094 [doi] AB - All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26) enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic arteries than in normal arteries. Databases were queried for nonsynonymous CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophagelike cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions, as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis. FAU - Krivospitskaya, Olesya AU - Krivospitskaya O AD - Department of Clinical Medicine, School of Health and Medical Sciences, Orebro University, Orebro, Sweden. FAU - Elmabsout, Ali Ateia AU - Elmabsout AA FAU - Sundman, Eva AU - Sundman E FAU - Soderstrom, Leif A AU - Soderstrom LA FAU - Ovchinnikova, Olga AU - Ovchinnikova O FAU - Gidlof, Andreas C AU - Gidlof AC FAU - Scherbak, Nikolai AU - Scherbak N FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Samnegard, Ann AU - Samnegard A FAU - Torma, Hans AU - Torma H FAU - Abdel-Halim, Samy M AU - Abdel-Halim SM FAU - Jansson, Jan-Hakan AU - Jansson JH FAU - Eriksson, Per AU - Eriksson P FAU - Sirsjo, Allan AU - Sirsjo A FAU - Olofsson, Peder S AU - Olofsson PS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120509 PL - England TA - Mol Med JT - Molecular medicine (Cambridge, Mass.) JID - 9501023 RN - 0 (RNA, Messenger) RN - 5688UTC01R (Tretinoin) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase) SB - IM MH - Alleles MH - Animals MH - Atherosclerosis/*genetics/*metabolism MH - Cell Line MH - Cytochrome P-450 Enzyme System/*genetics/metabolism MH - Female MH - Gene Expression MH - Genotype MH - Humans MH - Macrophages/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Protein Transport MH - RNA, Messenger/genetics/metabolism MH - Retinoic Acid 4-Hydroxylase MH - Transcription, Genetic/drug effects MH - Tretinoin/*metabolism/pharmacology PMC - PMC3388133 EDAT- 2012/03/15 06:00 MHDA- 2012/12/10 06:00 CRDT- 2012/03/15 06:00 PHST- 2012/02/28 00:00 [received] PHST- 2012/03/02 00:00 [accepted] PHST- 2012/03/15 06:00 [entrez] PHST- 2012/03/15 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] AID - molmed.2012.00094 [pii] AID - 10.2119/molmed.2012.00094 [doi] PST - epublish SO - Mol Med. 2012 May 9;18:712-8. doi: 10.2119/molmed.2012.00094. PMID- 22267482 OWN - NLM STAT- MEDLINE DCOM- 20120413 LR - 20181113 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 32 IP - 3 DP - 2012 Mar TI - Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction: a biological rheostat for fibroblast growth factor 2-mediated angiogenesis. PG - 696-703 LID - 10.1161/ATVBAHA.111.243998 [doi] AB - OBJECTIVE: Angiogenesis is regulated by the balance between pro- and antiangiogenic factors and by extracellular matrix protein interactions. Fibroblast growth factor 2 (FGF2) is a major proangiogenic inducer inhibited by the interaction with the soluble pattern recognition receptor long pentraxin 3 (PTX3). PTX3 is locally coexpressed with its ligand tumor necrosis factor-stimulated gene-6 (TSG-6), a secreted glycoprotein that cooperates with PTX3 in extracellular matrix assembly. Here, we characterized the effect of TSG-6 on PTX3/FGF2 interaction and FGF2-mediated angiogenesis. METHODS AND RESULTS: Solid phase binding and surface plasmon resonance assays show that TSG-6 and FGF2 bind the PTX3 N-terminal domain with similar affinity. Accordingly, TSG-6 prevents FGF2/PTX3 interaction and suppresses the inhibition exerted by PTX3 on heparan sulfate proteoglycan/FGF2/FGF receptor complex formation and on FGF2-dependent angiogenesis in vitro and in vivo. Also, endogenous PTX3 exerts an inhibitory effect on vascularization induced by FGF2 in a murine subcutaneous Matrigel plug assay, the inhibition being abolished in Ptx3-null mice or by TSG-6 treatment in wild-type animals. CONCLUSION: TSG-6 reverts the inhibitory effects exerted by PTX3 on FGF2-mediated angiogenesis through competition of FGF2/PTX3 interaction. This may provide a novel mechanism to control angiogenesis in those pathological settings characterized by the coexpression of TSG-6 and PTX3, in which the relative levels of these proteins may fine-tune the angiogenic activity of FGF2. FAU - Leali, Daria AU - Leali D AD - Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. FAU - Inforzato, Antonio AU - Inforzato A FAU - Ronca, Roberto AU - Ronca R FAU - Bianchi, Roberta AU - Bianchi R FAU - Belleri, Mirella AU - Belleri M FAU - Coltrini, Daniela AU - Coltrini D FAU - Di Salle, Emanuela AU - Di Salle E FAU - Sironi, Marina AU - Sironi M FAU - Norata, Giuseppe Danilo AU - Norata GD FAU - Bottazzi, Barbara AU - Bottazzi B FAU - Garlanda, Cecilia AU - Garlanda C FAU - Day, Anthony J AU - Day AJ FAU - Presta, Marco AU - Presta M LA - eng GR - 16539/Arthritis Research UK/United Kingdom GR - 18472/Arthritis Research UK/United Kingdom GR - G0701180/Medical Research Council/United Kingdom GR - G0701180(84646)/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120119 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Cell Adhesion Molecules) RN - 0 (Heparan Sulfate Proteoglycans) RN - 0 (Nerve Tissue Proteins) RN - 0 (Recombinant Proteins) RN - 0 (Serum Amyloid P-Component) RN - 0 (TNFAIP6 protein, human) RN - 0 (neuronal pentraxin) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 148591-49-5 (PTX3 protein) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Animals MH - Binding, Competitive MH - C-Reactive Protein/deficiency/genetics/*metabolism MH - CHO Cells MH - Cattle MH - Cell Adhesion Molecules/genetics/*metabolism MH - Chick Embryo MH - Cricetinae MH - Cricetulus MH - Female MH - Fibroblast Growth Factor 2/genetics/*metabolism MH - HEK293 Cells MH - Heparan Sulfate Proteoglycans/metabolism MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - *Neovascularization, Physiologic MH - Nerve Tissue Proteins/deficiency/genetics/*metabolism MH - Protein Binding MH - Protein Interaction Domains and Motifs MH - Protein Interaction Mapping MH - Recombinant Proteins/metabolism MH - Serum Amyloid P-Component/genetics/*metabolism MH - Surface Plasmon Resonance MH - Transfection PMC - PMC3551298 MID - EMS50901 OID - NLM: EMS50901 EDAT- 2012/01/24 06:00 MHDA- 2012/04/14 06:00 CRDT- 2012/01/24 06:00 PHST- 2012/01/24 06:00 [entrez] PHST- 2012/01/24 06:00 [pubmed] PHST- 2012/04/14 06:00 [medline] AID - ATVBAHA.111.243998 [pii] AID - 10.1161/ATVBAHA.111.243998 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):696-703. doi: 10.1161/ATVBAHA.111.243998. Epub 2012 Jan 19. PMID- 24278703 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20131126 LR - 20181113 IS - 2090-908X (Print) IS - 2090-908X (Linking) VI - 2012 DP - 2012 TI - Established and emerging approaches for the management of dyslipidaemia. PG - 482423 LID - 10.6064/2012/482423 [doi] AB - The key role of dyslipidaemia in determining cardiovascular disease (CVD) has been proved beyond reasonable doubt, and therefore several dietary and pharmacological approaches have been developed. The discovery of statins has provided a very effective approach in reducing cardiovascular risk as documented by the results obtained in clinical trials and in clinical practice. The current efficacy of statins or other drugs, however, comes short of providing the benefit that could derive from a further reduction of LDL cholesterol (LDL-C) in high-risk and very high risk patients. Furthermore, experimental data clearly suggest that other lipoprotein classes beyond LDL play important roles in determining cardiovascular risk. For these reasons a number of new potential drugs are under development in this area. Aim of this review is to discuss the available and the future pharmacological strategies for the management of dyslipidemia. FAU - Norata, Giuseppe Danilo AU - Norata GD AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano 20122 Milan, Italy ; Center for the Study of Atherosclerosis, Societa Italiana Studio Aterosclerosi, Ospedale Bassini, 20092 Cinisello Balsamo, Italy ; Centre for Diabetes, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London E12AT, UK. LA - eng PT - Journal Article PT - Review DEP - 20120910 PL - Egypt TA - Scientifica (Cairo) JT - Scientifica JID - 101589932 PMC - PMC3820450 EDAT- 2012/01/01 00:00 MHDA- 2012/01/01 00:01 CRDT- 2013/11/27 06:00 PHST- 2012/07/26 00:00 [received] PHST- 2012/08/26 00:00 [accepted] PHST- 2013/11/27 06:00 [entrez] PHST- 2012/01/01 00:00 [pubmed] PHST- 2012/01/01 00:01 [medline] AID - 10.6064/2012/482423 [doi] PST - ppublish SO - Scientifica (Cairo). 2012;2012:482423. doi: 10.6064/2012/482423. Epub 2012 Sep 10. PMID- 15350356 OWN - NLM STAT- MEDLINE DCOM- 20041014 LR - 20061115 IS - 0090-8258 (Print) IS - 0090-8258 (Linking) VI - 94 IP - 3 DP - 2004 Sep TI - Matrix metalloproteinase-26 (matrilysin-2) expression is high in endometrial hyperplasia and decreases with loss of histological differentiation in endometrial cancer. PG - 661-70 AB - OBJECTIVE: Matrix metalloproteinases (MMPs) are key players in the degradation of extracellular matrix and basement membranes, and are thus important in tumor invasion. Recently, MMP-26 (endometase), a novel matrilysin-type member of the MMP family, was cloned from an endometrial tumor. This study examines the expression of MMP-26 mRNA in hyperplastic, premalignant and malignant endometrial samples, and compares with normal endometrial tissue. METHODS: Endometrial carcinoma samples (19) were histologically classified as well, intermediately and poorly differentiated. Samples with hyperplasia (n = 15) were classified as simple, complex, or complex with atypia. Normal endometrial specimens (n = 39) were classified according to an ideal 28-day menstrual cycle and subsequently grouped in the early, middle, and late parts of the cycle. All samples were analyzed using in situ hybridization and real time PCR. The probes used for in situ hybridization and real time PCR recognized non-overlapping sequences. MMP-26 protein was localized by immunohistochemistry. RESULTS: MMP-26 mRNA was exclusively localized in the epithelial component of normal, hyperplastic, premalignant, as well as malignant samples. It was not found in the stroma of any tissue category. Quantifications with real time PCR as well as semi-quantifications of the in situ hybridization signal revealed maximal levels in normal tissue at midcycle and in endometrial hyperplasia both with and without atypia. The amount of MMP-26 mRNA decreased progressively with loss of histological differentiation in malignant samples. Immunostaining localized MMP-26 in epithelial glandular and luminal cells, in vessel walls, and in tumor cells. Since the pattern of MMP-26 expression mimicked that of ER-alpha, we searched the MMP-26 promoter region for a potential estrogen response element (ERE). A sequence at position -130 to -116 had high homology to the consensus sequence of an ERE. Based on these observations, we suggest that ER-alpha is involved in regulation of the MMP-26 gene. CONCLUSIONS: MMP-26 mRNA is selectively localized in the epithelial compartment of normal, hyperplastic, and malignant endometrial tissue. Expression is high in normal and hyperplastic endometria, but is downregulated in the late part of the cycle and in malignant tumors. The expression pattern of MMP-26 mRNA mimics that of ER-alpha, and the promoter region of the MMP-26 gene has a potential ERE. FAU - Pilka, R AU - Pilka R AD - Department of Obstetrics and Gynecology, University Hospital, S-221 85 Lund, Sweden. FAU - Norata, G D AU - Norata GD FAU - Domanski, H AU - Domanski H FAU - Andersson, C AU - Andersson C FAU - Hansson, S AU - Hansson S FAU - Eriksson, P AU - Eriksson P FAU - Casslen, B AU - Casslen B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (RNA, Messenger) RN - EC 3.4.24.- (MMP26 protein, human) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.- (Matrix Metalloproteinases, Secreted) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Differentiation/physiology MH - Cell Transformation, Neoplastic/metabolism/pathology MH - Endometrial Hyperplasia/*enzymology/pathology MH - Endometrial Neoplasms/*enzymology/pathology MH - Female MH - Humans MH - In Situ Hybridization MH - Matrix Metalloproteinases/*biosynthesis/genetics MH - Matrix Metalloproteinases, Secreted MH - Middle Aged MH - Precancerous Conditions/enzymology/pathology MH - RNA, Messenger/biosynthesis/genetics EDAT- 2004/09/08 05:00 MHDA- 2004/10/16 09:00 CRDT- 2004/09/08 05:00 PHST- 2003/11/04 00:00 [received] PHST- 2004/09/08 05:00 [pubmed] PHST- 2004/10/16 09:00 [medline] PHST- 2004/09/08 05:00 [entrez] AID - 10.1016/j.ygyno.2004.05.024 [doi] AID - S0090825804003348 [pii] PST - ppublish SO - Gynecol Oncol. 2004 Sep;94(3):661-70. doi: 10.1016/j.ygyno.2004.05.024.