Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, 443000, Hubei, China.
Mol Biol Rep. 2014 Jan;41(1):555-61. doi: 10.1007/s11033-013-2891-x. Epub 2013 Dec 12.
MicroRNAs are extensively involved in the pathogenesis of major cardiovascular diseases by suppressing target gene expression. Recent studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R) induced myocardial injury. However, the specific function of miR-22 in myocardial I/R injury is far from clear nowadays. The present study was designed to determine the role of miR-22 in myocardial I/R injury and investigate the underlying cardio-protective mechanism. The rat myocardial I/R injury model was induced by occluding the left anterior descending coronary artery for 30 min followed by 12 h reperfusion. As predicted, adenovirus-mediated miR-22 overexpression markedly reduced the release of creatine kinase and lactate dehydrogenase, infarct size and cardiomyocytes apoptosis. Moreover, CREB binding protein (CBP) as a potential miR-22 target by bioinformatics was significantly inhibited after miR-22 transfection. We also found that p53 acetylation activity, pro-apoptotic related genes Bax and p21 levels were all decreased associated with the down-regulation of CBP. In conclusion, our data demonstrate that miR-22 could inhibit apoptosis of cardiomyocytes through one of its targets, CBP. Thus, miR-22 may constitute a new therapeutic target for the prevention of myocardial I/R injury.
微小 RNA 通过抑制靶基因的表达广泛参与主要心血管疾病的发病机制。最近的研究报道，微小 RNA-22（miR-22）可能与缺血再灌注（I/R）引起的心肌损伤有关。然而，miR-22 在心肌 I/R 损伤中的具体功能尚不清楚。本研究旨在确定 miR-22 在心肌 I/R 损伤中的作用，并探讨其潜在的心脏保护机制。通过结扎左前降支冠状动脉 30 min 再灌注 12 h 诱导大鼠心肌 I/R 损伤模型。正如预测的那样，腺病毒介导的 miR-22 过表达显著减少了肌酸激酶和乳酸脱氢酶的释放、梗死面积和心肌细胞凋亡。此外，miR-22 转染后，CREB 结合蛋白（CBP）作为一种潜在的 miR-22 靶标，通过生物信息学被显著抑制。我们还发现，p53 乙酰化活性、促凋亡相关基因 Bax 和 p21 水平均随着 CBP 的下调而降低。综上所述，我们的数据表明，miR-22 可以通过其靶标之一 CBP 抑制心肌细胞凋亡。因此，miR-22 可能成为预防心肌 I/R 损伤的新治疗靶点。
