{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:21:20Z","timestamp":1790824880829,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004362","name":"Swiss Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_175546"],"award-info":[{"award-number":["310030_175546"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_166576)"],"award-info":[{"award-number":["310030_166576)"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alfred and Annemarie von Sick Grants for Translational and Clinical Research Cardiology and Oncology"},{"name":"Hans-Peter Wild to the Foundation for Cardiovascular Research\u2013Zurich Heart House"},{"name":"H.H. Sheikh Khalifa bin Hamad Al Thani Foundation Assistant Professorship at the Faculty of Medicine, University of Zurich"},{"name":"European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme","award":["759248"],"award-info":[{"award-number":["759248"]}]},{"name":"German Research Foundation (DFG","award":["SFB834"],"award-info":[{"award-number":["SFB834"]}]},{"name":"German Research Foundation (DFG","award":["75732319"],"award-info":[{"award-number":["75732319"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Arterial thrombosis as a result of plaque rupture or erosion is a key event in acute cardiovascular events. Sirtuin 5 (SIRT5) belongs to the lifespan-regulating sirtuin superfamily and has been implicated in acute ischaemic stroke and cardiac hypertrophy. This project aims at investigating the role of SIRT5 in arterial thrombus formation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Sirt5 transgenic (Sirt5Tg\/0) and knock-out (Sirt5\u2212\/\u2212) mice underwent photochemically induced carotid endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) were treated with SIRT5 silencing-RNA (si-SIRT5) as well as peripheral blood mononuclear cells from acute coronary syndrome (ACS) patients and non-ACS controls (case\u2013control study, total n\u2009=\u2009171) were used to increase the translational relevance of our data. Compared to wild-type controls, Sirt5Tg\/0 mice displayed accelerated arterial thrombus formation following endothelial-specific damage. Conversely, in Sirt5\u2212\/\u2212 mice, arterial thrombosis was blunted. Platelet function was unaltered, as assessed by ex vivo collagen-induced aggregometry. Similarly, activation of the coagulation cascade as assessed by vascular and plasma tissue factor (TF) and TF pathway inhibitor expression was unaltered. Increased thrombus embolization episodes and circulating D-dimer levels suggested augmented activation of the fibrinolytic system in Sirt5\u2212\/\u2212 mice. Accordingly, Sirt5\u2212\/\u2212 mice showed reduced plasma and vascular expression of the fibrinolysis inhibitor plasminogen activator inhibitor (PAI)-1. In HAECs, SIRT5-silencing inhibited PAI-1 gene and protein expression in response to TNF-\u03b1. This effect was mediated by increased AMPK activation and reduced phosphorylation of the MAP kinase ERK 1\/2, but not JNK and p38 as shown both in vivo and in vitro. Lastly, both PAI-1 and SIRT5 gene expressions are increased in ACS patients compared to non-ACS controls after adjustment for cardiovascular risk factors, while PAI-1 expression increased across tertiles of SIRT5.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>SIRT5 promotes arterial thrombosis by modulating fibrinolysis through endothelial PAI-1 expression. Hence, SIRT5 may be an interesting therapeutic target in the context of atherothrombotic events.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa268","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T19:14:13Z","timestamp":1599160453000},"page":"2275-2288","source":"Crossref","is-referenced-by-count":28,"title":["Sirtuin 5 promotes arterial thrombosis by blunting the fibrinolytic system"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-7975","authenticated-orcid":false,"given":"Luca","family":"Liberale","sequence":"first","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"},{"name":"First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3052-9493","authenticated-orcid":false,"given":"Alexander","family":"Akhmedov","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-8078","authenticated-orcid":false,"given":"Nikolaos I","family":"Vlachogiannis","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Framlington Place, NE2 4HH Newcastle upon Tyne,\u00a0UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3580-352X","authenticated-orcid":false,"given":"Nicole R","family":"Bonetti","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"},{"name":"Department of Internal Medicine, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanasa","family":"Nageswaran","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melroy X","family":"Miranda","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5448-407X","authenticated-orcid":false,"given":"Yustina M","family":"Puspitasari","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Costantino","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-7844","authenticated-orcid":false,"given":"Francesco","family":"Paneni","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland"},{"name":"Department of Cardiology, University Heart Center, 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-8729","authenticated-orcid":false,"given":"Fabrizio","family":"Montecucco","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino Genoa\u2014Italian Cardiovascular Network, L.go R. 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Tyne,\u00a0UK"},{"name":"Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Lourou 4-2, 115 28 Athens,\u00a0Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-0825","authenticated-orcid":false,"given":"Konstantinos","family":"Stellos","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Framlington Place, NE2 4HH Newcastle upon Tyne,\u00a0UK"},{"name":"Department of Cardiology, Newcastle Hospitals NHS Foundation Trust, Freeman Rd, High Heaton, Newcastle upon Tyne NE7 7DN,\u00a0UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0523-0695","authenticated-orcid":false,"given":"Giovanni G","family":"Camici","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, 8952 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