MicroRNA-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats

ObjectiveMicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, have been implicated in the development and progression of heart failure.MethodsThe present study was undertaken to determine the roles of miR-133a on the anatomical, hemodynamic and fibrosis of heart in the chronic heart failure rats, and the downstream signaling pathway.ResultsThe expression of miR-133a in the heart of chronic heart failure from patients or rats was decreased. The miR-133a mimic and miR-133a overexpression caused a decrease in the heart weight/body weight (HW/BW) and LVEDP, and an increase in the LVSP and +LV dP/dtmax in the chronic heart failure rats. However, the miR-133a inhibitor promoted the HW/BW and LVEDP, and caused a decrease in the LVSP and LV dP/dtmax in the chronic heart failure rats. The miR-133a mimic and miR-133a overexpression significantly caused a decrease in the fibrosis of heart in chronic heart failure rats. The Akt inhibitor TCN abolished the effects of miR-133a on the HW/BW and LVEDP decrease, LVSP and LV dP/dtmax increase in the chronic heart failure rats. The miR-133a increased the expression of phosphorylated Akt in the heart of chronic heart failure rats.ConclusionThese results demonstrated that miR-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats.