The Effects And Mechanisms Of MicroRNA-99a On Heart Remodeling After Myocardial Infarction

Aims:MicroRNAs(miRNAs)are involved in various critical functions,including the regulation of cellular apoptosis and autophagy.The aim of the present study was to investigate the role of microRNA-99a(miR-99a)in heart remodeling after ischemia infarction.Methods and Results:Expression of miR-99a was down-regulated in neonatal mice ventricular myocytes(NMVMs)exposed to hypoxia using Taqman quantitative reverse transcriptase-polymerase chain reaction(RT-PCR)analysis.Gain-of-function approach was used to investigate miR-99a therapeutic potential on myocytes apoptosis,autophagy and heart remodeling after myocardial infarction in vivo and in vitro.Overexpressed miR-99a decreased hypoxia-mediated apoptosis in cultured NMVMs.To investigate whether overexpression of miR-99a in vivo could improve cardiac function in ischemic heart,adult C57/BL6 mice undergoing MI were randomized into two groups and were intra-myocardially injected with lenti-99a-GFP or lenti-GFP,respectively.Four weeks after MI,lenti-99a-GFP group showed a significant improvement in both left ventricular(LV)function and survival ratio compared with the lenti-GFP group(control group).Furhtermore,our study showed inhibited mTOR expression,decreased cellular apoptosis and increased autophagy in cardiomyocytes of lenti-99a-GFP group.Conclusion:Our results demonstrate that miR-99a overexpression improves both cardiac function and survival ratio in a murine model of MI by preventing cell apoptosis and increasing autophagy via an mTOR/P70/S6K signaling pathway.These findings suggest that miR-99a plays a cardioprotective role in post-infarction LV remodeling and increased expression of miR-99a may have a therapeutic potential in ischemic heart disease.