Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94143, USA.
J Exp Med. 2011 Mar 14;208(3):549-60. doi: 10.1084/jem.20101547. Epub 2011 Mar 7.
Acute myocardial infarction (MI) involves necrotic and apoptotic loss of cardiomyocytes. One strategy to salvage ischemic cardiomyocytes is to modulate gene expression to promote cell survival without disturbing normal cardiac function. MicroRNAs (miRNAs) have emerged as powerful regulators of multiple cellular processes, including apoptosis, suggesting that regulation of miRNA function could serve a cardioprotective function. In this study, we report that miR-24 (miRNA-24) expression is down-regulated in the ischemic border zone of the murine left ventricle after MI. miR-24 suppresses cardiomyocyte apoptosis, in part by direct repression of the BH3-only domain-containing protein Bim, which positively regulates apoptosis. In vivo expression of miR-24 in a mouse MI model inhibited cardiomyocyte apoptosis, attenuated infarct size, and reduced cardiac dysfunction. This antiapoptotic effect on cardiomyocytes in vivo was partially mediated by Bim. Our results suggest that manipulating miRNA levels during stress-induced apoptosis may be a novel therapeutic strategy for cardiac disease.
急性心肌梗死（MI）涉及心肌细胞的坏死和凋亡性丢失。挽救缺血性心肌细胞的一种策略是调节基因表达，以促进细胞存活而不干扰正常的心脏功能。微小 RNA（miRNA）已成为多种细胞过程（包括细胞凋亡）的强大调节剂，这表明 miRNA 功能的调节可能具有心脏保护功能。在这项研究中，我们报告说，MI 后小鼠左心室缺血边界区的 miR-24（miRNA-24）表达下调。miR-24 抑制心肌细胞凋亡，部分是通过直接抑制 BH3 结构域仅包含蛋白 Bim 的表达来实现的，Bim 蛋白正向调节细胞凋亡。在小鼠 MI 模型中体内表达 miR-24 抑制心肌细胞凋亡，减轻梗死面积，减少心脏功能障碍。这种体内对心肌细胞的抗凋亡作用部分是由 Bim 介导的。我们的研究结果表明，在应激诱导的细胞凋亡过程中操纵 miRNA 水平可能是心脏疾病的一种新的治疗策略。
