{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:11:07Z","timestamp":1790655067652,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Miguel Servet contract CP13\/00221 from the \u201cInstituto de Salud Carlos III-FEDER\u201d"],"award-info":[{"award-number":["Miguel Servet contract CP13\/00221 from the \u201cInstituto de Salud Carlos III-FEDER\u201d"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Fondo de Investigaciones Sanitarias [PI18\/01875],"],"award-info":[{"award-number":["Fondo de Investigaciones Sanitarias [PI18\/01875],"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PhD grant"],"award-info":[{"award-number":["PhD grant"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["sara borrell"],"award-info":[{"award-number":["sara borrell"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR- 16-CE14-0021-01"],"award-info":[{"award-number":["ANR- 16-CE14-0021-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fight-HF Avenir Investment Program","award":["ANR-15-RHUS-0004"],"award-info":[{"award-number":["ANR-15-RHUS-0004"]}]},{"name":"FP7-funded COST ADMIRE network","award":["BM1301"],"award-info":[{"award-number":["BM1301"]}]},{"name":"Region Ile de France ARDoc","award":["a PhD grant"],"award-info":[{"award-number":["a PhD grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitral valve prolapse (MVP) patients develop myocardial fibrosis that is not solely explained by volume overload, but the pathophysiology has not been defined. Mineralocorticoid receptor antagonists (MRAs) improve cardiac function by decreasing cardiac fibrosis in other heart diseases. We examined the role of MRA in myocardial fibrosis associated with myxomatous degeneration of the mitral valve. Myocardial fibrosis has been analyzed in a mouse model of mitral valve myxomatous degeneration generated by pharmacological treatment with Nordexfenfluramine (NDF) in the presence of the MRA spironolactone. In vitro, adult human cardiac fibroblasts were treated with NDF and spironolactone. In an experimental mouse, MRA treatment reduced interstitial\/perivascular fibrosis and collagen type I deposition. MRA administration blunted NDF-induced cardiac expression of vimentin and the profibrotic molecules galectin-3\/cardiotrophin-1. In parallel, MRA blocked the increase in cardiac non-fibrillar proteins such as fibronectin, aggrecan, decorin, lumican and syndecan-4. The following effects are blocked by MRA: in vitro, in adult human cardiac fibroblasts, NDF-treatment-induced myofibroblast activation, collagen type I and proteoglycans secretion. Our findings demonstrate, for the first time, the contribution of the mineralocorticoid receptor (MR) to the development of myocardial fibrosis associated with mitral valve myxomatous degeneration. MRA could be a therapeutic approach to reduce myocardial fibrosis associated with MVP.<\/jats:p>","DOI":"10.3390\/ijms21155372","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T07:31:45Z","timestamp":1596007905000},"page":"5372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Beneficial Effects of Mineralocorticoid Receptor Antagonism on Myocardial Fibrosis in an Experimental Model of the Myxomatous Degeneration of the Mitral Valve"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0604-9289","authenticated-orcid":false,"given":"Jaime","family":"Ibarrola","sequence":"first","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4046","authenticated-orcid":false,"given":"Mattie","family":"Garaikoetxea","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Garcia-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Matilla","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Jover","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1746-9580","authenticated-orcid":false,"given":"Benjamin","family":"Bonnard","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, USPC, Universit\u00e9 Paris Descartes, Universit\u00e9 Paris Diderot, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cuesta","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Fern\u00e1ndez-Celis","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Jaisser","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, USPC, Universit\u00e9 Paris Descartes, Universit\u00e9 Paris Diderot, 75013 Paris, France"},{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, UMR 1116, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"L\u00f3pez-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, UMR 1116, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,28]]},"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: New insights into disease progression, genetics, and molecular 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