Activation of cardiac fibroblasts by ethanol is blocked by TGF-ß inhibition.
Alcohol Clin Exp Res
; 37(8): 1286-94, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23528014
ABSTRACT
BACKGROUND:
Alcohol abuse is the second leading cause of dilated cardiomyopathy, a disorder specifically referred to as alcoholic cardiomyopathy (ACM). Rodent and human studies have revealed cardiac fibrosis to be a consequence of ACM, and prior studies by this laboratory have associated this occurrence with elevated transforming growth factor-beta (TGF-ß) and activated fibroblasts (myofibroblasts). To date, there have been no other studies to investigate the direct effect of alcohol on the cardiac fibroblast.METHODS:
Primary rat cardiac fibroblasts were cultured in the presence of ethanol (EtOH) and assayed for fibroblast activation by collagen gel contraction, alpha-smooth muscle actin (α-SMA) expression, migration, proliferation, apoptosis, collagen I and III, and TGF-ß expression. The TGF-ß receptor type 1 inhibitor compound SB 431542 and a soluble recombinant TGF-ßII receptor (RbII) were used to assess the role of TGF-ß in the response of cardiac fibroblasts to EtOH.RESULTS:
Treatment for cardiac fibroblasts with EtOH at concentrations of 100 mg/dl or higher resulted in fibroblast activation and fibrogenic activity after 24 hours including an increase in contraction, α-SMA expression, migration, and expression of collagen I and TGF-ß. No changes in fibroblast proliferation or apoptosis were observed. Inhibition of TGF-ß by SB 431542 and RbII attenuated the EtOH-induced fibroblast activation.CONCLUSIONS:
EtOH treatment directly promotes cardiac fibroblast activation by stimulating TGF-ß release from fibroblasts. Inhibiting the action of TGF-ß decreases the fibrogenic effect induced by EtOH treatment. The results of this study support TGF-ß to be an important component in cardiac fibrosis induced by exposure to EtOH.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Alcoólica
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Depressores do Sistema Nervoso Central
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Fator de Crescimento Transformador beta
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Etanol
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Fibroblastos
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article