{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:45:59Z","timestamp":1787237159334,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030_175546"],"award-info":[{"award-number":["310030_175546"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swiss Heart Foundation"},{"name":"Faculty of Medicine"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["322900939"],"award-info":[{"award-number":["322900939"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["322900939 and LE 1350\/9"],"award-info":[{"award-number":["322900939 and LE 1350\/9"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Low-grade inflammation couples dysmetabolic states to insulin resistance and atherosclerotic cardiovascular (CV) disease (ASCVD). Selective sodium\u2013glucose co-transporter 2 (SGLT-2) inhibition by empagliflozin improves clinical outcomes in patients with ASCVD independently of its glucose lowering effects. Yet, its mechanism of action remains largely undetermined. Here, we aimed to test whether empagliflozin affects arterial thrombus formation in baseline (BSL) conditions or low-grade inflammatory states, a systemic milieu shared among patients with ASCVD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Sixteen-week-old C57BL\/6 mice were randomly assigned to acute administration of empagliflozin (25 mg\/kg body weight) or vehicle, of which a subgroup was pre-treated biweekly over 4 weeks with super-low-dose lipopolysaccharide (LPS; 5 ng\/kg body weight), before carotid thrombosis was induced by photochemical injury. The between-group difference in Doppler-flow probe detected time-to-occlusion remained within the predefined equivalence margin (\u0394 = |10.50|), irrespective of low-grade inflammation (95% confidence interval, \u20139.82 to 8.85 and \u20139.20 to 9.69), while glucose dropped by 1.64 and 4.84 mmoL\/L, respectively. Ex vivo platelet aggregometry suggested similar activation status, corroborated by unchanged circulating platelet-factor 4 plasma levels. In concert, carotid PAI-1 expression and tissue factor (TF) activity remained unaltered upon SGLT-2 inhibition, and no difference in plasma D-dimer levels was detected, suggesting comparable coagulation cascade activation and fibrinolytic activity. In human aortic endothelial cells pre-treated with LPS, empagliflozin neither changed TF activity nor PAI-1 expression. Accordingly, among patients with established ASCVD or at high CV risk randomized to a daily dose of 10 mg empagliflozin signatures of thrombotic (i.e. TF) and fibrinolytic activity (i.e. PAI-1) remained unchanged, while plasma glucose declined significantly during 3 months of follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SGLT-2 inhibition by empagliflozin does not impact experimental arterial thrombus formation, neither under BSL conditions nor during sustained low-grade inflammation, and has no impact on proxies of thrombotic\/fibrinolytic activity in patients with ASCVD. The beneficial pleiotropic effects of empagliflozin are likely independent of pathways mediating arterial thrombosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvac126","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T04:08:03Z","timestamp":1661141283000},"page":"843-856","source":"Crossref","is-referenced-by-count":14,"title":["SGLT-2 inhibition by empagliflozin has no effect on experimental arterial thrombosis in a murine model of low-grade inflammation"],"prefix":"10.1093","volume":"119","author":[{"given":"Luca","family":"Liberale","sequence":"first","affiliation":[{"name":"Center for Molecular Cardiology, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa , 16132 Genoa , 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Switzerland"}],"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, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ministrini","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"Internal Medicine, Angiology and Atherosclerosis, Department of Medicine and Surgery, University of Perugia , 06123 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-8729","authenticated-orcid":false,"given":"Fabrizio","family":"Montecucco","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa , 16132 Genoa , Italy"},{"name":"IRCCS Ospedale Policlinico San Martino Genoa \u2013 Italian Cardiovascular Network , 16132 Genoa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-634X","authenticated-orcid":false,"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Aachen, RWTH , 52074 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lehrke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Aachen, RWTH , 52074 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels-Ulrik K","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Aachen, RWTH , 52074 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg H","family":"Beer","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"Department of Internal Medicine, Cantonal Hospital of Baden , 5404 Baden , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-9918","authenticated-orcid":false,"given":"Florian A","family":"Wenzl","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, 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, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"University Heart Center, Department of Cardiology, University Hospital Zurich , 8091 Zurich , Switzerland"},{"name":"Department of Research and Education, University Hospital Zurich , 8091 Zurich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"L\u00fcscher","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"Royal Brompton and Harefield Hospitals and Imperial College , SW3 6NP London , UK"}],"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, University of Zurich , Wagistrasse 12, 8952 Schlieren , Switzerland"},{"name":"University Heart Center, Department of Cardiology, University Hospital Zurich , 8091 Zurich 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