Wu Chan, Hong Yi-Xiang, Zhang Xiao-Cheng, Li Jing-Zhou, Li Yu-Ting, Xie Jun, Wang Rui-Ying, Wang Yan, Li Gang
Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361000, China.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
Free Radic Biol Med. 2025 Jan;226:117-128. doi: 10.1016/j.freeradbiomed.2024.11.030. Epub 2024 Nov 16.
Myocardial infarction-triggered myocardial remodeling is fatal for therapies. The miR-30 family is an essential component of several physiological and pathological processes. Previous studies have proved that the miR-30 family may contribute to regulating myocardial infarction. This study aimed to demonstrate that the combination of miR-30a-5p and mitochondrial metabolism recapitulates the critical features for remodeling post-myocardial infarction. Using gain- and loss-of-function of miR-30a-5p in mice, we found miR-30a-5p is highly expressed in the heart and is reduced in infarcted hearts. Further evidence showed that miR-30a-5p acts as a protective molecule to maintain myocardial remodeling, fibrosis, and mitochondrial structure. Mitochondrial function, ATP production, and mitochondrial respiratory chain proteins were positively regulated by miR-30a-5p. Mechanistically, alterations in these properties depend on SIRT1, which modulates miR-30a-5p-regulated mitochondrial metabolism. Remarkably, reactivation of SIRT1 prevented miR-30a-5p deficiency-aggravated myocardial infarction-induced myocardial remodeling. These data identified miR-30a-5p as a critical modulator of mitochondrial function in cardiomyocytes and revealed that the miR-30a-5p-SIRT1-mitochondria network is essential for myocardial infarction-induced cardiac remodeling.
心肌梗死引发的心肌重塑对治疗来说是致命的。miR-30家族是多个生理和病理过程的重要组成部分。先前的研究已证明miR-30家族可能有助于调节心肌梗死。本研究旨在证明miR-30a-5p与线粒体代谢的结合概括了心肌梗死后重塑的关键特征。通过在小鼠中对miR-30a-5p进行功能获得和功能缺失实验，我们发现miR-30a-5p在心脏中高表达，而在梗死心脏中表达降低。进一步的证据表明，miR-30a-5p作为一种保护分子，可维持心肌重塑、纤维化和线粒体结构。miR-30a-5p对线粒体功能、ATP生成及线粒体呼吸链蛋白具有正向调节作用。从机制上讲，这些特性的改变取决于SIRT1，它调节miR-30a-5p介导的线粒体代谢。值得注意的是，SIRT1的重新激活可防止miR-30a-5p缺乏加剧的心肌梗死诱导的心肌重塑。这些数据确定miR-30a-5p是心肌细胞线粒体功能的关键调节因子，并揭示了miR-30a-5p-SIRT1-线粒体网络对心肌梗死诱导的心脏重塑至关重要。
