{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T02:18:25Z","timestamp":1794104305746,"version":"4.8.0"},"reference-count":60,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":59,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100008666","name":"La Marat\u00f2 de TV3","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>Innovative biomarkers are needed to improve the management of patients with type 2 diabetes mellitus (T2DM). Blood circulating miRNAs have been proposed as a potential tool to detect T2DM complications, but the lack of tissue specificity, among other reasons, has hampered their translation to clinical settings. Extracellular vesicle (EV)-shuttled miRNAs have been proposed as an alternative approach. Here, we adapted an immunomagnetic bead\u2013based method to isolate plasma CD31+ EVs to harvest vesicles deriving from tissues relevant for T2DM complications. Surface marker characterization showed that CD31+ EVs were also positive for a range of markers typical of both platelets and activated endothelial cells. After characterization, we quantified 11 candidate miRNAs associated with vascular performance and shuttled by CD31+ EVs in a large (n = 218) cross-sectional cohort of patients categorized as having T2DM without complications, having T2DM with complications, and control subjects. We found that 10 of the tested miRNAs are affected by T2DM, while the signature composed by miR-146a, -320a, -422a, and -451a efficiently identified T2DM patients with complications. Furthermore, another CD31+ EV-shuttled miRNA signature, i.e., miR-155, -320a, -342-3p, -376, and -422a, detected T2DM patients with a previous major adverse cardiovascular event. Many of these miRNAs significantly correlate with clinical variables held to play a key role in the development of complications. In addition, we show that CD31+ EVs from patients with T2DM are able to promote the expression of selected inflammatory mRNAs, i.e., CCL2, IL-1\u03b1, and TNF\u03b1, when administered to endothelial cells in vitro. Overall, these data suggest that the miRNA cargo of plasma CD31+ EVs is largely affected by T2DM and related complications, encouraging further research to explore the diagnostic potential and the functional role of these alterations.<\/jats:p>","DOI":"10.2337\/db20-0199","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T20:45:19Z","timestamp":1603485919000},"page":"240-254","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":64,"title":["CD31+ Extracellular Vesicles From Patients With Type 2 Diabetes Shuttle a miRNA Signature Associated With Cardiovascular Complications"],"prefix":"10.2337","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-2658","authenticated-orcid":false,"given":"Francesco","family":"Prattichizzo","sequence":"first","affiliation":[{"name":"IRCCS MultiMedica, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"De Nigris","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9947-6778","authenticated-orcid":false,"given":"Jacopo","family":"Sabbatinelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche e Molecolari, Universit\u00e0 Politecnica delle Marche, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche e Molecolari, Universit\u00e0 Politecnica delle Marche, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"CIBERDEM, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelina","family":"P\u00e1rrizas","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"CIBERDEM, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Crespo","sequence":"additional","affiliation":[{"name":"Cytometry and Cell Sorting Facility, Centre Esther Koplowitz, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Baranzini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosangela","family":"Spiga","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d of Catanzaro, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elettra","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d of Catanzaro, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Rippo","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche e Molecolari, Universit\u00e0 Politecnica delle Marche, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Domenico","family":"Procopio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche e Molecolari, Universit\u00e0 Politecnica delle Marche, Ancona, Italy"},{"name":"Centre of Clinical Pathology and Innovative Therapy, IRCCS - INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0465-2949","authenticated-orcid":false,"given":"Anna","family":"Novials","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain"},{"name":"CIBERDEM, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Bonfigli","sequence":"additional","affiliation":[{"name":"Scientific Direction, IRCCS - INRCA, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Istituto per l\u2019Endocrinologia e l\u2019Oncologia Sperimentale \u201cG. 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