{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:12:57Z","timestamp":1781716377267,"version":"3.54.5"},"reference-count":63,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research (MIUR) program \u201cDepartments of Excellence 2018\u20132022\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) could be involved in the onset of systemic sclerosis (SSc) through the modulation of vascular function. Anyway, available data are contradictory, and further investigation would be necessary to clarify this aspect. Here, we characterized circulating EVs isolated from SSc patients and evaluated their effects on human vascular endothelial cells (HUVECs) and smooth muscle cells. In EVs from 13 complicated and 27 uncomplicated SSc patients and five healthy controls (HCs), we analyzed the size, concentration, and surface marker expression. In addition, EVs were used to stimulate HUVECs, and we evaluated cell viability, mitochondrial membrane potential, and nitric oxide (NO) and mitochondrial reactive oxygen species (MitoROS) release. In smooth muscle cells, the effects of EVs on calcium movement were examined. The results showed that the EVs of SSc patients expressed markers of T-lymphocyte\/platelet\/endothelial cell origin and were larger and more concentrated than those from HCs. In addition, the EVs of SSc patients reduced cell viability and mitochondrial membrane potential and increased NO and MitoROS release in HUVECs and intracellular calcium in smooth muscle cells. In conclusion, we found a specific pattern for EVs isolated from SSc patients, which could have a pathogenic role through direct actions on endothelial and smooth muscle cells.<\/jats:p>","DOI":"10.3390\/ijms26062380","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T04:29:59Z","timestamp":1741321799000},"page":"2380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of Circulating Vesicles of Complicated and Uncomplicated Systemic Sclerosis Patients and Their Role in Vascular Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-259X","authenticated-orcid":false,"given":"Elena","family":"Grossini","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-8736","authenticated-orcid":false,"given":"Mattia","family":"Bellan","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Azienda Ospedaliera Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"},{"name":"CAAD, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Azienda Ospedaliera Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-2574","authenticated-orcid":false,"given":"Sakthipriyan","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-4688","authenticated-orcid":false,"given":"Mohammad Mostafa","family":"Ola Pour","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mennuni","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Azienda Ospedaliera Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"D\u2019Amario","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Azienda Ospedaliera Universitaria Maggiore della Carit\u00e0, 28100 Novara, 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Orientale, 28100 Novara, Italy"},{"name":"UPO Biobank, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-9158","authenticated-orcid":false,"given":"Pier Paolo","family":"Sainaghi","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Azienda Ospedaliera Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"},{"name":"CAAD, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Azienda Ospedaliera Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-0155","authenticated-orcid":false,"given":"Mario","family":"Pirisi","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of 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