Wu Yu-Xian, Xu Rong-Yu, Jiang Ling, Chen Xiang-Yan, Xiao Xiong-Jian
Department of Critical Care Medicine, Quanzhou First Hospital, Quanzhou, 362000, Fujian Province, China.
Department of Thoracic Surgery, Quanzhou First Hospital, Quanzhou, 362000, Fujian Province, China.
Cardiovasc Drugs Ther. 2023 Dec;37(6):1065-1076. doi: 10.1007/s10557-021-07304-w. Epub 2022 Apr 30.
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.
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.
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.
Inhibited miR-30a-5p inhibits CHF progression via the SIRT1-mediated NF-κB/NLRP3 signaling pathway.
微小RNA-30a-5p（miR-30a-5p）已被确定为心力衰竭的标志物；然而，其在慢性心力衰竭（CHF）中的功能机制仍不清楚。我们旨在研究miR-30a-5p靶向沉默调节蛋白1（SIRT1）通过核因子-κB/核苷酸结合寡聚化结构域样受体3（NF-κB/NLRP3）信号通路在CHF心肌重塑中的作用。
采用主动脉缩窄法建立CHF大鼠模型。测定CHF大鼠中miR-30a-5p、SIRT1及NF-κB/NLRP3信号通路相关因子的表达。然后分别用改变的miR-30a-5p或SIRT1处理CHF大鼠，以探讨它们在心脏功能、心肌功能、炎症反应、病理变化和心肌细胞凋亡中的作用。证实了miR-30a-5p与SIRT1之间的结合关系。
CHF大鼠心肌组织中miR-30a-5p上调而SIRT1下调。抑制miR-30a-5p或过表达SIRT1可改善CHF大鼠的心脏和心肌功能，抑制炎症反应，减轻病理变化并抑制心肌细胞凋亡。miR-30a-5p靶向SIRT1以调节NF-κB/NLRP3信号通路。在CHF大鼠中，下调miR-30a-5p和沉默SIRT1可逆转下调miR-30a-5p的有益作用。
抑制miR-30a-5p通过SIRT1介导的NF-κB/NLRP3信号通路抑制CHF进展。
