{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T21:40:31Z","timestamp":1789854031841,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:00:00Z","timestamp":1495152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ASDIA (Assistance Service DIAb\u00e8te) company"},{"name":"University Hospital of Strasbourg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Islet transplantation is associated with early ischaemia\/reperfusion, localized coagulation and redox\u2010sensitive endothelial dysfunction. In animal models, islet cytoprotection by activated protein C (aPC) restores islet vascularization and protects graft function, suggesting that aPC triggers various lineages. aPC also prompts the release of endothelial MP that bear EPCR, its specific receptor. Microparticles (MP) are plasma membrane procoagulant vesicles, surrogate markers of stress and cellular effectors. We measured the cytoprotective effects of aPC on endothelial and insulin\u2010secreting Rin\u2010m5f \u03b2\u2010cells and its role in autocrine and paracrine MP\u2010mediated cell crosstalk under conditions of oxidative stress. MP from aPC\u2010treated primary endothelial (EC) or \u03b2\u2010cells were applied to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated Rin\u2010m5f. aPC activity was measured by enzymatic assay and ROS species by dihydroethidium. The capture of PKH26\u2010stained MP and the expression of EPCR were probed by fluorescence microscopy and apoptosis by flow cytometry. aPC treatment enhanced both annexin A1 (ANXA1) and PAR\u20101 expression in EC and to a lesser extent in \u03b2\u2010cells. MP from aPC\u2010treated EC (eM<jats:sub>aPC<\/jats:sub>) exhibited high EPCR and annexin A1 content, protected \u03b2\u2010cells, restored insulin secretion and were captured by 80% of \u03b2 cells in a phosphatidylserine and ANXA1\u2010dependent mechanism. eMP activated EPCR\/PAR\u20101 and ANXA1\/FPR2\u2010dependent pathways and up\u2010regulated the expression of EPCR, and of FPR2\/ALX, the ANXA1 receptor. Cytoprotection was confirmed in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated rat islets with increased viability (62% <jats:italic>versus<\/jats:italic> 48% H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), reduced apoptosis and preserved insulin secretion in response to glucose elevation (16 <jats:italic>versus<\/jats:italic> 5 ng\/ml insulin per 10 islets). MP may prove a promising therapeutic tool in the protection of transplanted islets.<\/jats:p>","DOI":"10.1111\/jcmm.13191","type":"journal-article","created":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T11:18:56Z","timestamp":1495192736000},"page":"2759-2772","source":"Crossref","is-referenced-by-count":14,"title":["Endothelial microparticles released by activated protein C protect beta cells through EPCR\/PAR1 and annexin A1\/FPR2 pathways in islets"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6561-8384","authenticated-orcid":false,"given":"Guillaume","family":"Kreutter","sequence":"first","affiliation":[{"name":"EA7293 Vascular and Tissular Stress in Transplantation Federation of Translational Medicine of Strasbourg Faculty of Medicine University of Strasbourg Illkirch France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Kassem","sequence":"additional","affiliation":[{"name":"EA7293 Vascular and 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