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: Joaquim Fernández-Solà, Meritxell Lluis, Emilio Sacanella, Ramón Estruch, Emilia Antúnez, Alvaro Urbano-Márquez
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 35 Issue 7 Pg. 1220-9 (Jul 2011) ISSN: 1530-0277 [Electronic] England
• PMID: 21463333 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 by the Research Society on Alcoholism.

Chemical References

• Myostatin

Topics

• Adult
• Aged
• Alcoholism (metabolism, pathology)
• Cardiomyopathy, Alcoholic (metabolism, pathology)
• Cell Proliferation
• Chronic Disease
• Female
• Humans
• Hypertension (metabolism, pathology)
• Male
• Middle Aged
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Myostatin (biosynthesis, metabolism)
• Up-Regulation (physiology)