Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction

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Title:	Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction
Authors:	Chang, Wei-Ting Lin, Yu-Wen Chen, Chin-Yu Chen, Zhih-Cherng Shih, Jhih-Yuan Wu, Chia-Ching Luo, Chwan-Yau Liu, Ping-Yen
Contributors:	National Cheng Kung University Chi Mei Hospital Southern Taiwan University of Science & Technology Chi Mei Hospital Department of Health and Nutrition, Chia Nan University of Pharmacy & Science National Cheng Kung University National Cheng Kung University Hospital Kaohsiung Medical University
Keywords:	heart-failure oxidative stress spironolactone fibrosis disease
Date:	2022
Issue Date:	2023-12-11 13:57:50 (UTC+8)
Publisher:	MDPI
Abstract:	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-especially when strained-and 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.
Relation:	CELLS, v.11, n.17, pp.2750
Appears in Collections:	[Dept. of Health and Nutrition (including master's program)] Periodical Articles

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