Velvet Antler Ameliorates Cardiac Function by Restoring Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats With Heart Failure After Myocardial Infarction.

Haoyue Shi,Yanjun Li,Xiang Xiao,Li Huang,Tianzi Zhao,Lin Li,Jiajun Qiao,Haojun Zhang,Jiayun Wu

doi:10.3389/fphar.2021.621194

Abstract

Objective: Velvet antler (VA; cornu cervi pantotrichum), a well-known traditional Chinese medicine, has been shown to exert cardioprotective effects. The purpose of this study was to investigate the effect of VA on heart failure (HF) caused by ischemia-reperfusion, and explore its possible mechanism from the regulation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 alpha (SERCA2a). Methods: A rat model of HF was established by ligating the left anterior descending coronary artery of male Sprague–Dawley rats (n = 88). One week after surgery, VA (200, 400, or 800 mg/[kg day−1]) or enalapril (1 mg/[kg day−1]) was administered daily for the next 4 weeks. Heart function was detected by echocardiography and histopathological analysis. The serum BNP level was measured by ELISA, and the expression of SERCA2a, PLB, PLB-Ser16, and PKA was determined by western blotting. SERCA2a and PLB mRNA levels were determined by real-time quantitative PCR. Results: Compared with the sham group, cardiac function in the HF group, including the serum BNP level, heart mass index, myocardial collagen deposition, and left ventricular ejection fraction, was markedly reduced; however, these changes could be reversed by VA treatment. In addition, VA (200 mg/[kg·d−1]) inhibited the decrease of SERCA2a and PLB mRNA levels and SERCA2a, PLB, PLB-Ser16, and PKA protein expression and restored the activity of SERCA2a and PKA. Enalapril affected only PLB protein expression. Conclusion: VA can improve myocardial fibrosis and ventricular remodeling in rats, thereby helping to restore cardiac function. The underlying mechanism may be related to the upregulation of the expression and activation of PKA and PLB and the restoration of the expression and activity of SERCA2a.

Highlights

Heart failure (HF), which affects between 1 and 2% of the world’s adult population (Tanai and Frantz, 2015), is a complex clinical syndrome caused by ventricular filling or the ejection of blood (Yancy et al, 2013)
We further explored the mechanism by which velvet antlers (VA) improves cardiac function in rats with HF after myocardial infarction, and found that it likely involves the restoration of sarcoplasmic/endoplasmic reticulum Ca2+ATPase 2 alpha (SERCA2a) activity
Enalapril was used as a positive control as it belongs to the angiotensin-converting enzyme (ACE) inhibitor drug class—cornerstone drugs for the treatment of HF (Consensus Trial Study Group, 1987)—and because studies have shown that enalapril can alter the contractile performance and arrhythmogenicity of healthy myocardium in rats by upregulating SERCA2a (Matus et al, 2015)

Summary

Introduction

Heart failure (HF), which affects between 1 and 2% of the world’s adult population (Tanai and Frantz, 2015), is a complex clinical syndrome caused by ventricular filling or the ejection of blood (Yancy et al, 2013). 4 million people in China are estimated to have HF (Guo et al, 2018), while in the United States the figure is nearly 5.1 million (Go et al, 2013). This highlights the urgent need to identify new and effective approaches for the treatment of HF. The activity of sarcoplasmic/endoplasmic reticulum Ca2+ATPase 2 alpha (SERCA2a) tightly regulates cardiac contractility by performing active reuptake of cytoplasmic Ca2+. If SERCA2a expression and PLB phosphorylation are reduced, Ca2+ uptake into the sarcoplasmic reticulum (SR) will be negatively affected, thereby impairing the contractile performance of the heart (Sitsel et al, 2019). A reduction in SERCA2a activity can lead to the progressive deterioration of cardiac contractility in patients with HF

Methods

Results

Conclusion