Yu-Xian Wu1, Rong-Yu Xu2, Ling Jiang3, Xiang-Yan Chen1, Xiong-Jian Xiao4. 1. Department of Critical Care Medicine, Quanzhou First Hospital, Quanzhou, 362000, Fujian Province, China. 2. Department of Thoracic Surgery, Quanzhou First Hospital, Quanzhou, 362000, Fujian Province, China. 3. Department of Cardiovascular Medicine, The First Hospital of Nanping, Nanping, 353000, Fujian Province, China. 4. Department of Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Fuzhou, 350000, Fujian, China. Xiaoxiongjian1999@163.com.
Abstract
OBJECTIVE: MicroRNA-30a-5p (miR-30a-5p) has been identified as a marker of heart failure; however, its functional mechanisms in chronic heart failure (CHF) remain unknown. We aim to investigate the role of miR-30a-5p targeting sirtuin-1 (SIRT1) in myocardial remodeling in CHF via the nuclear factor-κB/NOD-like receptor 3 (NF-κB/NLRP3) signaling pathway. METHODS: CHF rat models were established using aortic coarctation. The expression of miR-30a-5p, SIRT1, and the NF-κB/NLRP3 signaling pathway-related factors in CHF rats was determined. The CHF rats were then respectively treated with altered miR-30a-5p or SIRT1 to explore their roles in cardiac function, myocardial function, inflammatory response, pathological changes, and cardiomyocyte apoptosis. The binding relation between miR-30a-5p and SIRT1 was confirmed. RESULTS: MiR-30a-5p was upregulated whereas SIRT1 was downregulated in myocardial tissues of CHF rats. MiR-30a-5p inhibition or SIRT1 overexpression improved cardiac and myocardial function, and suppressed the inflammatory response, alleviated pathological changes and inhibited cardiomyocyte apoptosis in CHF rats. MiR-30a-5p targeted SIRT1 to regulate the NF-κB/NLRP3 signaling pathway. In CHF rats, downregulated miR-30a-5p and silenced SIRT1 could reverse the beneficial effects of downregulated miR-30a-5p. CONCLUSION: Inhibited miR-30a-5p inhibits CHF progression via the SIRT1-mediated NF-κB/NLRP3 signaling pathway.
OBJECTIVE: MicroRNA-30a-5p (miR-30a-5p) has been identified as a marker of heart failure; however, its functional mechanisms in chronic heart failure (CHF) remain unknown. We aim to investigate the role of miR-30a-5p targeting sirtuin-1 (SIRT1) in myocardial remodeling in CHF via the nuclear factor-κB/NOD-like receptor 3 (NF-κB/NLRP3) signaling pathway. METHODS: CHF rat models were established using aortic coarctation. The expression of miR-30a-5p, SIRT1, and the NF-κB/NLRP3 signaling pathway-related factors in CHF rats was determined. The CHF rats were then respectively treated with altered miR-30a-5p or SIRT1 to explore their roles in cardiac function, myocardial function, inflammatory response, pathological changes, and cardiomyocyte apoptosis. The binding relation between miR-30a-5p and SIRT1 was confirmed. RESULTS: MiR-30a-5p was upregulated whereas SIRT1 was downregulated in myocardial tissues of CHF rats. MiR-30a-5p inhibition or SIRT1 overexpression improved cardiac and myocardial function, and suppressed the inflammatory response, alleviated pathological changes and inhibited cardiomyocyte apoptosis in CHF rats. MiR-30a-5p targeted SIRT1 to regulate the NF-κB/NLRP3 signaling pathway. In CHF rats, downregulated miR-30a-5p and silenced SIRT1 could reverse the beneficial effects of downregulated miR-30a-5p. CONCLUSION: Inhibited miR-30a-5p inhibits CHF progression via the SIRT1-mediated NF-κB/NLRP3 signaling pathway.