Inhibiting miR-205 Alleviates Cardiac Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Function, and Apoptosis

• Published in: Oxidative medicine and cellular longevity 2021, Vol.2021 (1), p.9986506-9986506
• Main Authors: Xu, Yuerong, Guo, Wangang, Zeng, Di, Fang, Yexian, Wang, Runze, Guo, Dong, Qi, Bingchao, Xue, Yugang, Xue, Feng, Jin, Zuolin, Li, Yan, Zhang, Mingming
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Cardiac function; Cardiomyocytes; Cardiovascular disease; Gene expression; Genomes; Heart attacks; Ischemia; Laboratory animals; Male; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; Mortality; Myocardial Infarction - metabolism; Myocardial Ischemia - genetics; Myocardial Ischemia - metabolism; Myocardial Reperfusion Injury - metabolism; Myocytes, Cardiac - metabolism; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Quality control; Transmission electron microscopy
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2021/9986506

Background. miR-205 is important for oxidative stress, mitochondrial dysfunction, and apoptosis. The roles of miR-205 in cardiac ischemia/reperfusion (I/R) injury remain unknown. The aim of this research is to reveal whether miR-205 could regulate cardiac I/R injury by focusing upon the oxidative stress, mitochondrial function, and apoptosis. Methods. Levels of miR-205 and Rnd3 were examined in the hearts with I/R injury. Myocardial infarct size, cardiac function, oxidative stress, mitochondria function, and cardiomyocyte apoptosis were detected in mice with myocardial ischemia/reperfusion (MI/R) injury. The primary neonatal cardiomyocytes underwent hypoxia/reoxygenation (H/R) to simulate MI/R injury. Results. miR-205 levels were significantly elevated in cardiac tissues from I/R in comparison with those from Sham. In comparison with controls, levels of Rnd3 were significantly decreased in the hearts from mice with MI/R injury. Furthermore, inhibiting miR-205 alleviated MI/R-induced apoptosis, reduced infarct size, prevented oxidative stress increase and mitochondrial fragmentation, and improved mitochondrial functional capacity and cardiac function. Consistently, overexpression of miR-205 increased infarct size and promoted apoptosis, oxidative stress, and mitochondrial dysfunction in mice with MI/R injury. In cultured mouse neonatal cardiomyocytes, downregulation of miR-205 reduced oxidative stress in H/R-treated cardiomyocytes. Finally, inhibiting Rnd3 ablated the cardioprotective effects of miR-205 inhibitor in MI/R injury. Conclusions. We conclude that inhibiting miR-205 reduces infarct size, improves cardiac function, and suppresses oxidative stress, mitochondrial dysfunction, and apoptosis by promoting Rnd3 in MI/R injury. miR-205 inhibitor-induced Rnd3 activation is a valid target to treat MI/R injury.