{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:29:04Z","timestamp":1788791344849,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds pour la Chirurgie Cardiaque, Brussels, Belgium","award":["489639"],"award-info":[{"award-number":["489639"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Molecular mechanisms underlying the progression from compensated eccentric hypertrophy to heart failure in chronic aortic regurgitation (AR) remain poorly understood. We investigated associated transcriptional changes induced by chronic volume overload in an experimental model of severe AR. AR was induced in male Wistar rats (n = 10) by retrograde aortic valve perforation and compared with age-matched control rats (n = 8). Sixty days after surgery, cardiac remodeling was evaluated by echocardiography, invasive hemodynamics and myocardial gene-expression profiling using RT-qPCR. Chronic AR induced marked left ventricular dilatation and systolic dysfunction, consistent with decompensated eccentric hypertrophy. These functional alterations were accompanied by coordinated transcriptional changes involving pathways related to apoptosis, oxidative balance, metabolic regulation and calcium handling. AR hearts exhibited an increased BAX\/BCL2 ratio, together with reduced SOD2 and increased GPX1 expression, suggesting a transcriptional profile consistent with activation of pro-apoptotic and antioxidant responses. Metabolic remodeling was characterized by decreased AMPK\u03b11, PPAR\u03b3 and GLUT4 expression, together with increased OLR1 and 15-LOX. KLK10 expression was increased. Reduced SERCA2A expression was observed, consistent with transcriptional alterations involving calcium-handling pathways. Chronic AR is associated with marked structural and functional cardiac remodeling accompanied by coordinated transcriptional alterations across multiple pathways implicated in myocardial dysfunction. This provides potential molecular pathways for further investigation.<\/jats:p>","DOI":"10.3390\/ijms27177950","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Left Ventricular Molecular Signature in Chronic Aortic Regurgitation"],"prefix":"10.3390","volume":"27","author":[{"given":"Bachar","family":"El Oumeiri","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, H.U.B.\u2014Erasme University Hospital, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Laboratory of Physiology and Pharmacology, Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Laurence","family":"Dewachter","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Philippe","family":"Van de Borne","sequence":"additional","affiliation":[{"name":"Department of Cardiology, H.U.B.\u2014Erasme University Hospital, Route de Lennik 808, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Hubesch","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Jespers","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Stefanidis","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, H.U.B.\u2014Erasme University Hospital, Route de Lennik 808, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Mc Entee","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology, Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Experimental Laboratory of Intensive Care, Universit\u00e9 Libre de Bruxelles, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Vanden Eynden","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, H.U.B.\u2014Erasme University Hospital, Route de Lennik 808, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1136\/heartjnl-2014-307020","article-title":"The modern epidemiology of heart valve disease","volume":"102","author":"Coffey","year":"2016","journal-title":"Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1016\/j.jacc.2018.03.459","article-title":"Valvular Heart Disease in Patients \u226580 Years of Age","volume":"71","author":"Kodali","year":"2018","journal-title":"J. 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