MiR-214-3p Attenuates Sepsis-Induced Myocardial Dysfunction in Mice by Inhibiting Autophagy through PTEN/AKT/mTOR Pathway

Zhenzhen Sang,Shimin Dong,Pu Zhang,Yunxia Wei

doi:10.1155/2020/1409038

Abstract

Aims. More than half of the patients with sepsis would develop cardiac dysfunction, which is termed as sepsis-induced myocardial dysfunction (SIMD). Previous studies suggest that autophagy may play an important role in SIMD. The present study investigated whether miR-214-3p could attenuate SIMD by inhibiting autophagy. Main Methods. In this article, we investigated the role of autophagy in a mouse model of cecal ligation and puncture (CLP). The structure and function of hearts harvested from the mice were evaluated. Myocardial autophagy levels were detected with immunohistochemical, immunofluorescent, and Western blot. Key Findings. miR-214-3p can alleviate SIMD in septic mice by inhibiting the level of cardiac autophagy to attenuate myocardial dysfunction. Moreover, this study showed that miR-214-3p inhibited autophagy by silencing PTEN expression in the myocardial tissues of septic mice. Significance. This study showed that miR-214-3p attenuated SIMD through myocardial autophagy inhibition by silencing PTEN expression and activating the AKT/mTOR pathway. The present findings supported that miR-214-3p may be a potential therapeutic target for SIMD.

Highlights

Sepsis, which is characterised by a systemic inflammatory response syndrome, complications with multiple organ dysfunctions, and high incidence and mortality rates, is a leading cause of death in patients with severe infection worldwide [1]
A moderate level of autophagy is the key to reduce Sepsis-induced myocardial dysfunction (SIMD). miR-214 has been demonstrated to be protective for H2O2-induced cardiac myocyte injury [5] and sepsis-induced apoptosis of cardiomyocytes [6]
Our results demonstrated that the overexpression of miR-214-3p attenuates cecal ligation and puncture (CLP)-induced myocardial injury by inhibiting excessive autophagy

Summary

Introduction

Sepsis, which is characterised by a systemic inflammatory response syndrome, complications with multiple organ dysfunctions, and high incidence and mortality rates, is a leading cause of death in patients with severe infection worldwide [1]. Sepsis-induced myocardial dysfunction (SIMD) is an identified serious component of the sepsis-induced multiorgan failure, and it is associated with adverse outcomes and higher mortality [2]. The mechanisms that underlie sepsis-induced cardiomyopathy are not well-known. Excessive autophagy may exert adverse effects on cardiac function and cellular health [4]. MiR-214 has been demonstrated to be protective for H2O2-induced cardiac myocyte injury [5] and sepsis-induced apoptosis of cardiomyocytes [6]. One study has reported that miR-214-3p could play a protective role in Alzheimer’s disease by inhibiting neurons autophagy [7]. Whether miR-214 could regulate myocardial autophagy in septic mice remains unknown. We investigated the effect and mechanism of miR-214-3p in SIMD in the CLP-treated mice model

Methods

Discussion

Conclusion