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

Objective: MicroRNAs (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. Methods: The 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. Results: The 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/dt(max) 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/dt(max) 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. Conclusion: These results demonstrated that miR-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats. (C) 2015 Elsevier Masson SAS. All rights reserved.