Department of Cardiac Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Feb 4;53(2):140-148. doi: 10.1093/abbs/gmaa154.
Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3'-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.
心肌损伤仍然是一种严重的损害公共健康的疾病。临床上，心肌损伤常导致心脏功能障碍，严重时可导致死亡。缺血心肌组织的再灌注可以最大限度地减少急性心肌梗死（AMI）引起的损伤。microRNAs 在各种疾病中普遍被认识，并且经常参与心肌缺血/再灌注损伤的发展。然而，miR-431 在心肌损伤中的作用尚不清楚。在这项研究中，我们研究了 miR-431 在缺氧/复氧（H/R）下人原代心肌细胞凋亡和自噬中的潜在机制。H/R 处理降低了细胞活力，促进了细胞凋亡率，并下调了人原代心肌细胞中 miR-431 的表达。miR-431 抑制剂的下调通过靶向 ATG3 的 3'-非翻译区降低了人原代心肌细胞中 miR-431 的表达。pcDNA3.1-ATG3 上调 ATG3 的表达逆转了 miR-431 过表达对 H/R 处理后人原代心肌细胞活力和细胞凋亡的保护作用。更重要的是，H/R 处理促进了人原代心肌细胞中的自噬，而这种作用通过 miR-431 模拟物转染得到了极大缓解。我们的研究结果表明，miR-431 的过表达至少部分通过调节 ATG3 的表达来减轻 H/R 诱导的心肌损伤。
