{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:26:34Z","timestamp":1789619194463,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T00:00:00Z","timestamp":1662163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST 109-2326-B-384-001-MY3"],"award-info":[{"award-number":["MOST 109-2326-B-384-001-MY3"]}]},{"name":"Ministry of Science and Technology","award":["NHRI-EX111-11138SI"],"award-info":[{"award-number":["NHRI-EX111-11138SI"]}]},{"name":"National Health Research Institute","award":["MOST 109-2326-B-384-001-MY3"],"award-info":[{"award-number":["MOST 109-2326-B-384-001-MY3"]}]},{"name":"National Health Research Institute","award":["NHRI-EX111-11138SI"],"award-info":[{"award-number":["NHRI-EX111-11138SI"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote cardiac fibrosis. The mineralocorticoid receptor antagonist spironolactone is a potassium-sparing diuretic and a guideline-recommended therapy for HF, but whether it can ameliorate degenerative MR remains unknown. Herein, we investigate the efficacy of spironolactone in improving cardiac remodeling in MR-induced HF compared with that of a loop diuretic, furosemide. Using a novel and mini-invasive technique, we established a rat model of MR. We treated the rats with spironolactone or furosemide for twelve weeks. The levels of cardiac fibrosis, apoptosis, and stress-associated proteins were then measured. In parallel, we compared the cardiac remodeling of 165 patients with degenerative MR receiving either spironolactone or furosemide. Echocardiography was performed at baseline and at six months. In MR rats treated with spironolactone, left ventricular function\u2014especially when strained\u2014and the pressure volume relationship significantly improved compared to those of rats treated with furosemide. Spironolactone treatment demonstrated significant attenuation of cardiac fibrosis and apoptosis in left ventricular tissue compared to furosemide. Further, spironolactone suppressed the expression of apoptosis-, NADPH oxidase 4 (NOX4)- and inducible nitric oxide synthase (iNOS)-associated proteins. Similarly, compared with MR patients receiving furosemide those prescribed spironolactone demonstrated a trend toward reduction in MR severity and showed improvement in left ventricular function. Collectively, MR-induced cardiovascular dysfunction, including fibrosis and apoptosis, was effectively attenuated by spironolactone treatment. Our findings suggest a potential therapeutic option for degenerative MR-induced HF.<\/jats:p>","DOI":"10.3390\/cells11172750","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"2750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction"],"prefix":"10.3390","volume":"11","author":[{"given":"Wei-Ting","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan 71004, Taiwan"},{"name":"Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Chi-Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-5218","authenticated-orcid":false,"given":"Zhih-Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhih-Yuan","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan 71004, Taiwan"},{"name":"Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-8425","authenticated-orcid":false,"given":"Chia-Ching","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chwan-Yau","family":"Luo","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Yen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"ref_1","first-page":"e72","article-title":"2020 ACC\/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"143","author":"Otto","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e005971","DOI":"10.1161\/CIRCIMAGING.116.005971","article-title":"Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights","volume":"11","author":"Antoine","year":"2018","journal-title":"Circ Cardiovasc. 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