{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:45:04Z","timestamp":1789184704817,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Italian Ministry of Health","award":["RC2020-CA1B ID: 2757547"],"award-info":[{"award-number":["RC2020-CA1B ID: 2757547"]}]},{"DOI":"10.13039\/501100009700","name":"Fondazione Gigi e Pupa Ferrari","doi-asserted-by":"publisher","award":["FPF-14"],"award-info":[{"award-number":["FPF-14"]}],"id":[{"id":"10.13039\/501100009700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p \u2264 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.<\/jats:p>","DOI":"10.3390\/ijms22042102","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T21:15:01Z","timestamp":1613942101000},"page":"2102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation"],"prefix":"10.3390","volume":"22","author":[{"given":"Paola","family":"Songia","sequence":"first","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-9954","authenticated-orcid":false,"given":"Mattia","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Bioinformatics and Artificial Intelligence Facility (BioAI), Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Massaiu","sequence":"additional","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Moschetta","sequence":"additional","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"},{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Myasoedova","sequence":"additional","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Valerio","sequence":"additional","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"},{"name":"Dipartimento di Medicina Clinica e Chirurgia, Universit\u00e0 degli Studi di Napoli Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-6231","authenticated-orcid":false,"given":"Laura","family":"Fusini","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Department, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Gripari","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Department, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4400-0451","authenticated-orcid":false,"given":"Marco","family":"Zanobini","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-3379","authenticated-orcid":false,"given":"Paolo","family":"Poggio","sequence":"additional","affiliation":[{"name":"Unit for the Study of Aortic, Valvular and Coronary Pathologies, Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1161\/CIRCULATIONAHA.113.006702","article-title":"Epidemiology and Pathophysiology of Mitral Valve Prolapse","volume":"129","author":"Delling","year":"2014","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM199907013410101","article-title":"Prevalence and Clinical Outcome of Mitral-Valve Prolapse","volume":"341","author":"Freed","year":"1999","journal-title":"N. 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