MicroRNA-17-5p Downregulation Inhibits Autophagy and Myocardial Remodeling after Myocardial Infarction by Targeting STAT3

Abstract

Objective: Myocardial infarction (MI) is acknowledged as a major cause of heart disease related death in the world. This study aims to explore the function and mechanism of miR-17-5p-induced STAT3 in myocardial remodeling after MI.Methods: MI mice were infected by lentivirus antago-miR-17-5p vector. The expression of miR-17-5p in myocardial tissues was detected. The levels of STAT3 and specific markers of autophagy LC3-II/LC3-I, Beclin-1 and p62 were measured. Myocardial remodeling and scar size were assessed and cell apoptosis was determined. The binding of miR-17-5p and STAT3 was analyzed. The functions of miR-17-5p and STAT3 in autophagy and myocardial remodeling after MI were confirmed by functional rescue experiment after injecting STAT3 inhibitor S31-20.Results: Decreased fractional shortening, increased left ventricular systolic diameter and ventricular filling velocity were detected in MI mice. High expression of miR-17-5p was found in myocardial tissues after MI. The inhibition of miR-17-5p expression led to reduction of fibrosis of myocardial tissues, scarring, cardiomyocyte apoptosis, and expressions of LC3-II/LC3-I and Beclin-1, and increased p62 expression after MI. miR-17-5p targeted STAT3 and negatively regulated its expression. Inhibition of STAT3 level reversed the improving effect of antago-miR-17-5p on MI.Conclusion: Inhibition of miR-17-5p can inhibit myocardial autophagy through targeting STAT3, and then inhibit myocardial remodeling, thereby protecting myocardium after MI.