Overexpression of micro RNA ‐99a attenuates heart remodelling and improves cardiac performance after myocardial infarction

Micro RNA s are involved in the regulation of various cellular processes, including cell apoptosis and autophagy. Expression of micro RNA ‐99a (miR‐99a) is reduced in apoptotic neonatal mice ventricular myocytes ( NMVM s) subjected to hypoxia. We hypothesize that miR‐99a might restore cardiac function after myocardial infarction ( MI ) by up‐regulation of myocyte autophagy and apoptosis. We observed down‐regulated miR‐99a expression in NMVM s exposed to hypoxia using TaqMan quantitative reverse transcriptase‐polymerase chain reaction analysis ( RT ‐ PCR ). We also observed that miR‐99a overexpression decreased hypoxia‐mediated apoptosis in cultured NMVM s. To investigate whether overexpression of miR‐99a in vivo could improve cardiac function in ischaemic heart, adult C57/BL6 mice undergoing MI were randomized into two groups and were intra‐myocardially injected with lenti‐99a‐green fluorescent protein ( GFP ) or lenti‐ GFP (control). Four weeks after MI , lenti‐99a‐ GFP group showed significant improvement in both left ventricular ( LV ) function and survival ratio, as compared to the lenti‐ GFP group. Histological analysis, western blotting analysis and electron microscopy revealed decreased cellular apoptosis and increased autophagy in cardiomyocytes of lenti‐99a‐ GFP group. Furthermore, western blotting analysis showed inhibited mammalian target of rapamycin (m TOR ) expression in the border zones of hearts in miR‐99a‐treated group. 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 m TOR /P70/S6K signalling pathway. These findings suggest that miR‐99a plays a cardioprotective role in post‐infarction LV remodelling and increased expression of miR‐99a may have a therapeutic potential in ischaemic heart disease.