{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:28:18Z","timestamp":1767983298915,"version":"3.49.0"},"reference-count":119,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>miRNAs have recently attracted investigators\u2019 interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.<\/jats:p>","DOI":"10.3390\/ijms222212132","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T21:39:07Z","timestamp":1636493947000},"page":"12132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets"],"prefix":"10.3390","volume":"22","author":[{"given":"Francesco","family":"Nappi","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Centre Cardiologique du Nord de Saint-Denis, 93200 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-4689","authenticated-orcid":false,"given":"Adelaide","family":"Iervolino","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjeet Singh","family":"Avtaar Singh","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Glasgow G81 4DY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8178-7068","authenticated-orcid":false,"given":"Massimo","family":"Chello","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery, University Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. 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