MiR-129-5p improves cardiac function in rats with chronic heart failure through targeting HMGB1.

Abstract

Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p in chronic heart failure and the underlying mechanisms. The levels of miR-129-5p and HMGB1 in chronic heart failure patients (CHF) and normal controls were examined by RT-qPCR and ELISA. Cardiac function, hemodynamics parameters, oxidative stress, and inflammation factors were analyzed in CHF rat model after transfection of miR-129-5p or HMGB1. Dual-luciferase activity reporter assay was conducted to validate the interaction between miR-129-5p and HMGB1. Downregulation of miR-129-5p and upregulation of HMGB1 were observed in the serum of CHF patients, respectively. Transfection of miR-129-5p improved heart function and hemodynamic parameters, as well as attenuated oxidative stress and inflammation factors in CHF rats. We further confirmed that HMGB1 is a direct target of miR-129-5p. Transfection of miR-129-5p also decreased the mRNA and protein levels of HMGB1 in myocardial tissues of CHF rats. Overexpression of HMGB1 diminished the effects of miR-129-5p on ameliorating oxidative stress and inflammatory response in rats with CHF. Our findings suggest that miR-129-5p protects the heart by targeting HMGB1.