Inhibition of microRNA-146a attenuated heart failure in myocardial infarction rats.

Junjie He,Xiaoxuan Gong,Xiaozheng Song,Yong Li,Ying Lu

doi:10.1042/bsr20191732

Junjie He, Xiaoxuan Gong + Show 3 more

Open Access

https://doi.org/10.1042/bsr20191732

Copy DOI

Abstract

The aim of the present study was to determine the roles of microRNA (miR)-146a on myocardial infarction (MI)-induced heart failure and cardiac remodeling. Experiments were carried out in Sprague-Dawley rats treated with ligation of left coronary artery to induce heart failure, and in primary neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes treated with angiotensin (Ang) II. Four weeks after MI, rats were injected with miR-146a antagomiR or agomiR via tail vein. After 2 weeks of injection, the rats were killed. In MI rats, left ventricle (LV) ejection fraction and fractional shortening were reduced, and LV volumes in diastole and systole were increased, which were reversed by miR-146a antagomiR, and further exacerbated after miR-146a agomiR treatment. Administration of miR-146a antagomiR improved the decreases of LV ±dp/dtmax and LV systolic pressure (LVSP), and the increase in LV end-diastolic pressure (LVEDP) of MI rats, but miR-146a agomiR deteriorated the LV ±dp/dtmax, LVSP and LVEDP. The increases in the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen I and collagen III in the heart, and ST2 and norepinephrine in the serum of MI rats were inhibited by miR-146a antagomiR, but aggravated after miR-146a agomiR treatment. The increases of collagen I and collagen III levels induced by Ang II in CFs, and the increases of ANP and BNP levels induced by Ang II in cardiomyocytes were inhibited by miR-146a antagomiR, but aggravated by miR-146a agomiR. These results demonstrated that inhibition of miR-146a improved cardiac dysfunction and cardiac remodeling in heart failure rats.

Highlights

The prevalence of heart failure (HF) continues to rise over time with the aging population [1]
MiR-146a antagomiR injection via tail vein increased the reduction of ejection fraction (EF) (%) and fractional shortening (FS) (%), and reduced the increases of LV volumes in diastole (LVVd) and left ventricle volume (LVV) in heart failure rats (Figure 1A)
left ventricle (LV) +dp/dtmax, LV −dp/dtmax and LV systolic pressure (LVSP) were decreased in myocardial infarction (MI) rats, and miR-146a antagomiR injection increased the decreases of LV +dp/dtmax, LV −dp/dtmax and LVSP induced by MI

Summary

Introduction

The prevalence of heart failure (HF) continues to rise over time with the aging population [1]. HF, a complex syndrome defined by inadequate cardiac output to meet the metabolic demands of body organs, resulted from a wide range of congenital and acquired cardiovascular or metabolic diseases leading to structural and functional cardiac impairment [2,3]. Epidemiological studies have indicated numerous causative and risks factors of HF, including coronary artery disease, diabetes mellitus, valvular heart disease, hypertension, atrial fibrillation and obesity [4,5]. The understanding and discovery of miRNAs has raised the possibility of using circulating miRNA as biomarkers in cardiovascular disease (CVD) [15,16]. Increasing evidence has demonstrated that several miRNAs, including miR-146a, miR-190a, miR-1233, miR-193b-3p, miR-211-5p are dysregulated in human or experimental model with heart failure [4,17].

Objectives

Results

Conclusion