miR-1231 exacerbates arrhythmia by targeting calciumchannel gene CACNA2D2 in myocardial infarction.

MicroRNAs (miRNAs) are noncoding single-stranded RNAs of ~22 nucleotides suppressing a wide range of gene expression by direct degradation or translational inhibition of their target mRNAs. Acute myocardial infarction (AMI), a common cardiovascular disease mainly induced by coronary artery occlusion, can lead to the development of heart failure. Several recent findings have indicated that miRNAs might play vital roles in AMI, and some miRNAs have even been proposed as potential candidates for intervening AMI. However, the pathophysiological functions of miRNAs implicated in MI are still largely unidentified. Here, we show that miR-1231 is overexpressed both in human hearts after MI insults and in rat hearts with experimental MI compared with their healthy counterparts. Next, by using predictive strategy and gene expression array, cacna2d2 is identified as the target of miR-1231. In human and rat ischemic hearts, cacna2d2 expression is indeed suppressed by miR-1231. In addition, the inhibition of miR-1231 in vivo ameliorates arrhythmias in rat MI hearts; conversely, the forced overexpression of miR-1231 promotes arrhythmias. Furthermore, cacna2d2 knockdown alone induced arrhythmias in ischemic hearts, despite knockdown of miR-1231. Thus, these results indicate that miR-1231 exacerbates arrhythmia by inhibiting cacna2d2 in ischemic heart, which shed light on the important arrhythmogenic function of miR-1231 in MI and suggest it may serve as a potential antiarrhythmic target.