Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, PR China.
Curr Pharm Des. 2013;19(27):4865-73. doi: 10.2174/13816128113199990325.
MicroRNA-34a (miR-34a) promotes apoptosis via down-regulating many anti-apoptotic proteins. Aldehyde dehydrogenase 2 (ALDH2) is an anti-apoptotic enzyme whose activity decline associates with myocardial injury. We tested hypothesis that miR-34a might play a pro-apoptotic role in myocardial infarction (MI) by down-regulating ALDH2. MiR-34a was highly increased while ALDH2 expression was decreased after experimental MI. Overexpression of miR-34a in neonatal rat cardiomyocyte could significantly enhance apoptosis and down-regulate ALDH2 expression. In 293 cells, luciferase reporter assay results demonstrated that ALDH2 was a direct target of miR-34a. Serum miR-34a levels in acute myocardial infarction (AMI) patients and rats were significantly higher than healthy subjects and sham rats. Our results proved that miR-34a could promote cardiomyocyte apoptosis via negatively regulating ALDH2 and circulating miR-34a was increased in the condition of MI. Thus, miR-34a may constitute a new therapeutic target and diagnostic marker for patients with MI.
miR-34a（微小 RNA-34a）通过下调许多抗凋亡蛋白促进细胞凋亡。乙醛脱氢酶 2（ALDH2）是一种抗凋亡酶，其活性下降与心肌损伤有关。我们假设 miR-34a 可能通过下调 ALDH2 在心肌梗死（MI）中发挥促凋亡作用。在实验性 MI 后，miR-34a 的表达显著增加，而 ALDH2 的表达减少。在新生大鼠心肌细胞中过表达 miR-34a 可显著增强细胞凋亡并下调 ALDH2 的表达。在 293 细胞中，荧光素酶报告基因检测结果表明 ALDH2 是 miR-34a 的直接靶标。急性心肌梗死（AMI）患者和大鼠血清 miR-34a 水平明显高于健康受试者和假手术大鼠。我们的研究结果证明，miR-34a 可以通过负调控 ALDH2 促进心肌细胞凋亡，并且在 MI 情况下循环 miR-34a 水平升高。因此，miR-34a 可能成为 MI 患者的新治疗靶点和诊断标志物。
