{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:10:49Z","timestamp":1792455049277,"version":"4.5.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007368","name":"Fondazione Pisa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev\u2013Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev\u2013Rem during the late postoperative period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary MR patients (<jats:italic>n<\/jats:italic> = 19; age, 45\u201371 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev\u2013Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev\u2013Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, \u201321\u20135p, \u2013133a, and \u2013208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 \u03bcM for 48 h).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, <jats:italic>p<\/jats:italic> = 0.016), who showed lower cardiac mass index (\u201311%, <jats:italic>p<\/jats:italic> = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). <jats:italic>In vitro<\/jats:italic>, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary\/Conclusion<\/jats:title><jats:p>High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev\u2013Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev\u2013Rem after successful early surgical MVR.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.943068","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T11:06:43Z","timestamp":1659092803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve 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