Effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure by regulating TGF-β1/Smad3 signaling pathway.

Chun Xie,Yan Yang,Huanxin Qi,Lei Huan

doi:10.1042/bsr20200566

Abstract

Purpose: The present study set out to investigate the effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure (HF) and its mechanism.Methods: HF rat model and hypoxia/reoxygenation (H/R) cardiomyocyte model were established. miR-195-5p expression and transforming growth factor-β1 (TGF-β1)/signal transduction protein (Smad)3 signaling pathway in HF rats and H/R cardiomyocytes were interfered. miR-195-5p expression was tested by Rt-PCR, TGF-β1/Smad3 signaling pathway related proteins were detected by Western Blot, apoptosis of HF rat cardiomyocytes was tested by TUNEL, and apoptosis of cardiomyocytes induced by H/R was checked by flow cytometry.Results: miR-195-5p was lowly expressed in myocardium of HF rats, while TGF-β1 and Smad3 proteins were high-expressed. Up-regulating miR-195-5p expression could obviously inhibit cardiomyocyte apoptosis of HF rats, improve their cardiac function, and inhibit activation of TGF-β1/Smad3 signaling pathway. Up-regulation of miR-195-5p expression or inhibition of TGF-β1/Smad3 signaling pathway could obviously inhibit H/R-induced cardiomyocyte apoptosis. Dual-luciferase reporter enzyme verified the targeted relationship between miR-195-5p and Smad3.Conclusion: miR-195-5p can inhibit cardiomyocyte apoptosis and improve cardiac function in HF rats by regulating TGF-β1/Smad3 signaling pathway, which may be a potential target for HF therapy.

Highlights

Heart failure (HF) is a complex clinical syndrome in which the ejection or filling ability of left ventricle is damaged due to cardiac structure or dysfunction
We found a targeted relationship between miR-195-5p and Smad3 through online website prediction, so we speculated whether miR-195-5p could participate in HF’s development and progression by regulating transforming growth factor-β1 (TGF-β1)/Smad3 pathway
Compared with rats in the blank control group (BCG) and sham operation group (SOG), miR-195-5p was dramatically down-regulated in the HF group and miR-negative control (NC) group rats, while its expression in myocardium of rats in the HF+miR-195-5p-agomir group increased markedly (P

Summary

Introduction

Heart failure (HF) is a complex clinical syndrome in which the ejection or filling ability of left ventricle is damaged due to cardiac structure or dysfunction. HF is usually the final stage of various cardiovascular diseases [1,2]. With the changes of social environment and living habits, incidence of cardiovascular diseases is getting higher and higher, and almost any cardiovascular disease will eventually lead to the occurrence of HF. Apoptosis refers to a kind of spontaneous programmed cell death. Recent studies have found that cardiomyocyte apoptosis may be a crucial part of HF pathogenesis [5]. Previous studies [6] have shown that cardiomyocyte apoptosis is very obvious in patients with HF. It is quite significant to explore the mechanism of cardiomyocyte apoptosis in HF patients and how to prevent it for HF treatment. MiRNA has been found to be effective in all kinds of diseases, including cardiovascular

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Results

Conclusion