title: Increased myostatin activity and decreased myocyte proliferation in chronic alcoholic cardiomyopathy.
abstract: BACKGROUND
  Apoptosis mediates in alcohol-induced heart damage leading to cardiomyopathy (CMP). Myocyte proliferation may compensate for myocyte loss. Myostatin is upregulated after cardiac damage and by alcohol consumption thereby decreasing myocyte renewal. We assess the potential role of alcohol in inducing myocyte apoptosis as well as in inhibiting myocyte proliferation.
  
  
  METHODS
  Heart samples were obtained from organ donors, including 22 high alcohol consumers, 22 with hypertension, 8 with other causes of CMP, and 10 healthy donors. Evaluation included medical record with data on daily, recent and lifetime ethanol consumption, chest X-ray, left ventricular (LV) function assessed by two-dimensional echocardiography, and LV histology and immunohistochemistry. Apoptosis was evaluated by TUNEL, BAX, and BCL-2 assays. Myocyte proliferation was evaluated with Ki-67 assay. Myostatin activity was measured with a specific immunohistochemical assay. CMP was assessed by functional and histological criteria.
  
  
  RESULTS
  Alcoholic and hypertensive donors with CMP showed higher apoptotic indices than did their partners without CMP. Myostatin activity was higher in alcoholics than in controls, mainly in those with CMP. The increase in myostatin expression in alcoholic CMP was higher than in other groups. The Ki-67 proliferation index increased in all groups with CMP compared to those without CMP, with alcoholics showing a lower increase in this proliferation response.
  
  
  CONCLUSIONS
  Alcohol produces cardiac myocyte loss through apoptosis but also partially inhibits myocyte proliferation through myostatin up-regulation. The final result may suppose an imbalance in myocyte homeostasis, with a net loss in total ventricular myocyte mass and progressive ventricular dysfunction.
authors.affiliation: Alcohol Research Unit, Hospital Clinic, Institut d'Investigació August Pi i Sunyer, Department of Medicine, University of Barcelona, Barcelona, Spain. jfernand@clinic.ub.es
authors.forename: Joaquim
authors.initials: J
authors.lastname: Fernández-Solà
authors.forename: Meritxell
authors.initials: M
authors.lastname: Lluis
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacanella
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.forename: Emilia
authors.initials: E
authors.lastname: Antúnez
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Márquez
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism / Q000473:pathology; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D055435:Myostatin