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Increased myostatin activity and decreased myocyte proliferation in chronic alcoholic cardiomyopathy.
Alcohol Clin Exp Res ; 35(7): 1220-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21463333
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.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Cardiomiopatia Alcoólica / Miócitos Cardíacos / Proliferação de Células / Miostatina Limite: Adulto / Idoso / Feminino / Humanos / Masculino / Meia-Idade Idioma: Inglês Revista: Alcohol Clin Exp Res Ano de publicação: 2011 Tipo de documento: Artigo País de afiliação: Espanha