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| 標題: | Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction |
| 作者: | Chang, Wei-Ting
Lin, Yu-Wen
Chen, Chin-Yu
Chen, Zhih-Cherng
Shih, Jhih-Yuan
Wu, Chia-Ching
Luo, Chwan-Yau
Liu, Ping-Yen |
| 貢獻者: | 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 |
| 關鍵字: | heart-failure
oxidative stress
spironolactone
fibrosis
disease |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 13:57:50 (UTC+8) |
| 出版者: | MDPI |
| 摘要: | 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. |
| 關聯: | CELLS, v.11, n.17, pp.2750 |
| 顯示於類別: | [保健營養系(所) ] 期刊論文
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