title: Effects of the Activin A-Follistatin System on Myocardial Cell Apoptosis through the Endoplasmic Reticulum Stress Pathway in Heart Failure.
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.
  
  
  CONCLUSIONS
  Activin A-follistatin system participated in ERS-mediated myocardial cell apoptosis in HF.
authors.affiliation: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China. anne20081122@126.com.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China. megeren@163.com.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Mao
authors.affiliation: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China. yuanyuanlijiayu@163.com.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China. cian1984@163.com.
authors.forename: Fanglei
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China. pyang@jlu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D028341:Activins / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D005260:Female; D038681:Follistatin / Q000378:metabolism*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D007150:Immunohistochemistry; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D015415:Biomarkers; D038681:Follistatin; C422405:activin A; D028341:Activins; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D051742:Transcription Factor CHOP; D053148:Caspase 3
keywords: activin A; apoptosis; endoplasmic reticulum stress; follistatin; heart failure