Abstract 1883: MicroRNAs in the Early Phase of Acute Myocardial Infarction
Several recent reports have suggested that microRNAs (miRNAs) might play critical roles in acute myocardial infarction (AMI); however, the miRNA expression signature in the early phase of AMI has not been identified. In this study, the miRNA expression signature was investigated in rat hearts at 6 h after AMI. Compared with the expression signature in the noninfarcted areas, aberrant miRNA expression was a prominent characteristic in both border and infarcted areas. In infarcted areas, 38 miRNAs were differentially expressed. Among them, 21 miRNAs were upregulated and 17 miRNAs were downregulated. In the border areas, 33 miRNAs were differentially expressed (19 up and 14 down). Remarkably, miR-21 expression was significantly upregulated at both 6 h and 24 h after AMI in the border areas compared with that in other areas and in sham-opened hearts. Overexpression of miR-21 by adenovirus (Ad-miR-21) decreased myocardial infarct size by 23% at 24 h and decreased the dimension of left ventricles at two weeks after AMI. Using both gain-of-function and loss-of-function approaches, we have identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that is associated with its target gene PDCD4 and AP-1 pathway in cultured cardiac myocytes. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by the decreased cell apoptosis in the border and infacted areas of the infarcted hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI.