Beta3-Adrenergic Receptor Activation Alleviates Cardiac Dysfunction in Cardiac Hypertrophy by Regulating Oxidative Stress.

Mingming Zhang,Jing Liu,Jingxiao Yang,Yuerong Xu,Jianghong Chen,Rui Wang,Jianqiang Hu,Zikuan Wang,Chaoshi Qin,Qing Zou,Dong Guo,Xiaolin Niu

doi:10.1155/2021/3417242

Mingming Zhang, Jing Liu + Show 10 more

Open Access

https://doi.org/10.1155/2021/3417242

Copy DOI

Abstract

Background Excessive myocardial oxidative stress could lead to the congestive heart failure. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. β3-Adrenergic receptor (AR) could regulate cardiac dysfunction proved by recent researches. The molecular mechanism of β3-AR regulating oxidative stress, especially NADPH oxidase, remains to be determined. Methods Cardiac hypertrophy was constructed by the transverse aortic constriction (TAC) model. ROS and NADPH oxidase subunits expression were assessed after β3-AR agonist (BRL) or inhibitor (SR) administration in cardiac hypertrophy. Moreover, the cardiac function, fibrosis, heart size, oxidative stress, and cardiomyocytes apoptosis were also detected. Results β3-AR activation significantly alleviated cardiac hypertrophy and remodeling in pressure-overloaded mice. β3-AR stimulation also improved heart function and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis. Meanwhile, β3-AR stimulation inhibited superoxide anion production and decreased NADPH oxidase activity. Furthermore, BRL treatment increased the neuronal NOS (nNOS) expression in cardiac hypertrophy. Conclusion β3-AR stimulation alleviated cardiac dysfunction and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis by inhibiting NADPH oxidases. In addition, the protective effect of β3-AR is largely attributed to nNOS activation in cardiac hypertrophy.

Highlights

Despite the progress of therapeutic approaches, congestive heart failure (CHF) remains to be a high morbidity and mortality [1, 2]
Cardiac hypertrophy occurs as an adaptive response to maintain normal cardiac function and output by ameliorating ventricular wall stress
Our study suggested that sustained pressure overload for 3 weeks induced cardiac hypertrophy and increased the oxidative stress and cardiomyocytes apoptosis, which were associated with impaired cardiac function

Summary

Background

Excessive myocardial oxidative stress could lead to the congestive heart failure. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. β3-Adrenergic receptor (AR) could regulate cardiac dysfunction proved by recent researches. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. The molecular mechanism of β3-AR regulating oxidative stress, especially NADPH oxidase, remains to be determined. ROS and NADPH oxidase subunits expression were assessed after β3-AR agonist (BRL) or inhibitor (SR) administration in cardiac hypertrophy. The cardiac function, fibrosis, heart size, oxidative stress, and cardiomyocytes apoptosis were detected. Β3-AR activation significantly alleviated cardiac hypertrophy and remodeling in pressureoverloaded mice. Β3-AR stimulation improved heart function and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis. Β3-AR stimulation inhibited superoxide anion production and decreased NADPH oxidase activity. BRL treatment increased the neuronal NOS (nNOS) expression in cardiac hypertrophy. Β3-AR stimulation alleviated cardiac dysfunction and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis by inhibiting NADPH oxidases. The protective effect of β3-AR is largely attributed to nNOS activation in cardiac hypertrophy

Introduction

Methods

Results

Discussion