miR-1231 exacerbates arrhythmia by targeting calciumchannel gene CACNA2D2 in myocardial infarction
Jiefang Zhang1, Lili Wu1, Zhengwei Li1
1Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University of MedicineHangzhou 310016, Zhejiang, PR China.
Abstract:
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.
Insights
MicroRNAs (miRNAs) are key in heart attacks. This study found miR-1231 worsens arrhythmias after myocardial infarction by targeting cacna2d2, suggesting miR-1231 as an antiarrhythmic target.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in cardiovascular diseases.
- Acute myocardial infarction (AMI) can lead to heart failure, and the role of miRNAs in AMI is under investigation.
- The specific functions of many miRNAs in myocardial infarction (MI) pathophysiology remain unclear.
Purpose of the Study:
- To investigate the role of miR-1231 in the context of myocardial infarction (MI).
- To identify the target gene of miR-1231 and elucidate its mechanism in ischemic heart.
- To evaluate miR-1231 as a potential therapeutic target for arrhythmias post-MI.
Main Methods:
- Quantitative analysis of miR-1231 and cacna2d2 expression in human and rat MI hearts.
- Bioinformatic prediction and gene expression arrays to identify miR-1231 targets.
- In vivo studies involving inhibition or overexpression of miR-1231 and cacna2d2 knockdown in rat MI models.
Main Results:
- miR-1231 was found to be overexpressed in ischemic heart tissue.
- cacna2d2 was identified and validated as a direct target of miR-1231, with its expression suppressed by miR-1231 in MI.
- Inhibition of miR-1231 ameliorated arrhythmias, while its overexpression promoted them; cacna2d2 knockdown also induced arrhythmias.
Conclusions:
- miR-1231 exacerbates cardiac arrhythmias in the context of MI by inhibiting cacna2d2.
- This study highlights the significant arrhythmogenic role of miR-1231 in MI.
- miR-1231 presents a potential novel antiarrhythmic therapeutic target for myocardial infarction.
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