Resveratrol ameliorates myocardial fibrosis by regulating Sirt1/Smad3 deacetylation pathway in rat model with dilated cardiomyopathy

Qingquan Chen,Yu Zeng,Shuyu Zhang,Shirong Huang,Xiulin Yang,Min Chen,Yue Wu,Yameng Zhong

doi:10.1186/s12872-021-02401-y

Abstract

BackgroundThe aim of this study was to investigate the effects of Resveratrol (RSV) in rats with dilated cardiomyopathy (DCM).MethodsPorcine cardiac myosin was used to set up rat model with DCM. RSV (10 mg/kg in RSV-L group and 50 mg/kg in RSV-H group) or vehicle was administered to rats with DCM once daily from the 28th day till the 90th day after the first immunization. Cardiac function of rats was evaluated by echocardiographic analysis. The deposition of fibrous tissues in the hearts was evaluated by Masson and picrosirius red staining. The mRNA levels of collagen type I (Col I), collagen type III (Col III) and silence information regulator 1 (Sirt1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction of Sirt1 with Smad3 was revealed by coimmunoprecipitation.ResultsThe heart weight, heart weight/body weight ratio, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly increased in rats with DCM, and attenuated by RSV. RSV also positively decreased fibrosis, and the expression of Col I and Col III in the myocardium. The Sirt1 mRNA was significantly decreased in myosin-immunized hearts and was positively increased by RSV. The Sirt1 combined with Smad3 directly. Acetylation of Smad3 (Ac-Smad3) was significantly increased in DCM and was markedly decreased by RSV.ConclusionRSV effectively ameliorated myocardial fibrosis and improved cardiac function by regulating Sirt1/Smad3 deacetylation pathway in rat model with DCM.

Highlights

Dilated cardiomyopathy (DCM) is mainly characterized by complex remodeling of one or both ventricles with an associated increase in mass, volume and the architecture of the myocardium fibres, resulting in leftChen et al BMC Cardiovascular Disorders (2022) 22:17 risks
One is to reduce the activity of acetyltransferase, such as lysine acetyltransferase 5 can be suppressed by metformin [15] to decreased the Ac-Smad3 level, the other is to enhance the activation of histone deacetylase, such as the activation of histone deacetylase silence information regulator 1 (Sirt1) can be increased by resveratrol (RSV) [14], geniposide[8], carnosic acid [16] and nicotinamide riboside [17] to decreased the AcSmad3 level
Our results showed that heart weight, heart weight/body weight ratio, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly higher in rats with dilated cardiomyopathy (DCM) than controls, while body weight, left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were obvious lower in rats with DCM when compared to controls

Summary

Introduction

Dilated cardiomyopathy (DCM) is mainly characterized by complex remodeling of one or both ventricles with an associated increase in mass, volume and the architecture of the myocardium fibres, resulting in leftChen et al BMC Cardiovascular Disorders (2022) 22:17 risks. Studies found that Ac-Smad can be targeted by resveratrol (RSV) [14], geniposide [8], metformin [15], carnosic acid [16] and nicotinamide riboside [17] to ameliorate the tissue fibrosis. One is to reduce the activity of acetyltransferase, such as lysine acetyltransferase 5 can be suppressed by metformin [15] to decreased the Ac-Smad level, the other is to enhance the activation of histone deacetylase, such as the activation of histone deacetylase silence information regulator 1 (Sirt1) can be increased by resveratrol (RSV) [14], geniposide[8], carnosic acid [16] and nicotinamide riboside [17] to decreased the AcSmad level. The aim of this study was to investigate the effects of Resveratrol (RSV) in rats with dilated cardiomyopathy (DCM)

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