Effects of the Activin A-Follistatin System on Myocardial Cell Apoptosis through the Endoplasmic Reticulum Stress Pathway in Heart Failure.

Miao Liu,Ping Yang,Jiayu Li,Cuiying Mao,Fanglei Han

doi:10.3390/ijms18020374

Abstract

Background: A previous study suggested that activin A inhibited myocardial cell apoptosis. This study thus aimed to explore the effects of the activin A–follistatin system on myocardial cell apoptosis in heart failure (HF) rats in order to determine whether or not the mechanism operates through the endoplasmic reticulum stress (ERS) pathway. Methods: Myocardial infarction (MI) by vascular deprivation was used to induce HF. The enzyme-linked immunosorbent assay was used to detect activin A, follistatin and brain natriuretic peptide (BNP) contents in serum. Immunohistochemical staining for activin A, follistatin, CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP) and caspase-3 was performed on the myocardial tissue. The activin A-stimulated apoptosis of H9c2 cells was tested by flow cytometry. Western blot was used to detect the expression levels of activin A, follistatin and ERS-related proteins. Results: It was found that the high expression of activin A could cause activin A–follistatin system imbalance, inducing myocardial cell apoptosis via ERS in vivo. When HF developed to a certain stage, the expression of follistatin was upregulated to antagonize the expression of activin A. Activin A inhibited cardiomyocyte apoptosis with a low concentration and promoted apoptosis with a high concentration in vitro, also via ERS. Conclusion: Activin A–follistatin system participated in ERS-mediated myocardial cell apoptosis in HF.

Highlights

Activin is a subgroup of the transforming growth factor (TGF)-β superfamily
Activin A is a homodimeric glycoprotein consisting of two βA subunits, which has a number of important functions in embryonic development, cell proliferation, differentiation, reproductive biology, fibrosis, apoptosis, metabolism, homeostasis, immune response, wound repair, inflammation, and so on [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
A few studies showed that the over-expressed activin A in the skin of transgenic mice led to dermal fibrosis and excessive epidermal incrassation, whereas the over-expressed follistatin distinctly reduced the formation of the scar areas [5,18]

Summary

Introduction

Activin is a subgroup of the transforming growth factor (TGF)-β superfamily. It consists of two disulfide-linked activin β subunits (βA–βD) [1]. The imbalance of activin A–follistatin system participates in remodeling and repairing of tissues. A previous study suggested that activin A inhibited myocardial cell apoptosis. This study aimed to explore the effects of the activin A–follistatin system on myocardial cell apoptosis in heart failure (HF) rats in order to determine whether or not the mechanism operates through the endoplasmic reticulum stress (ERS) pathway. Results: It was found that the high expression of activin A could cause activin A–follistatin system imbalance, inducing myocardial cell apoptosis via ERS in vivo. Conclusion: Activin A–follistatin system participated in ERS-mediated myocardial cell apoptosis in HF

Objectives

Methods

Findings

Conclusion