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Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis.
Zhang, Ying-Min; Bo, Jacqueline; Taffet, George E; Chang, Jiang; Shi, Jianjian; Reddy, Anilkumar K; Michael, Lloyd H; Schneider, Michael D; Entman, Mark L; Schwartz, Robert J; Wei, Lei.
Afiliação
  • Zhang YM; The Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University, School of Medicine, R4 building, Rm. 370, 1044 West Walnut St., Indianapolis, Indiana 46202-5225, USA.
FASEB J ; 20(7): 916-25, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16675849
ABSTRACT
Ventricular myocyte hypertrophy is an important compensatory growth response to pressure overload. However, pathophysiological cardiac hypertrophy is accompanied by reactive fibrosis and remodeling. The Rho kinase family, consisting of ROCK1 and ROCK2, has been implicated in cardiac hypertrophy and ventricular remodeling. However, these previous studies relied heavily on pharmacological inhibitors,and not on gene deletion. Here we used ROCK1knockout (ROCK1-/-) mice to investigate role of ROCK1 in the development of ventricular remodeling induced by transverse aortic banding. We observed that ROCK1 deletion did not impair compensatory hypertrophic response induced by pressure overload. However, ROCK1-/- mice exhibited reduced perivascular and interstitial fibrosis, which was observed at 3 wk but not at 1 wk after the banding. The reduced fibrosis in the myocardium of ROCK1-/- mice was closely associated with reduced expression of a variety of extracellular matrix (ECM) proteins and fibrogenic cytokines such as TGFbeta2 and connective tissue growth factor. This inhibitory effect of ROCK1 deletion on pathophysiological induction of fibrogenic cytokines was further confirmed in the myocardium of transgenic mice with cardiomyocyte-specific overexpression of Gq. Thus, these results indicate that ROCK1 contributes to the development of cardiac fibrosis and induction of fibrogenic cytokines in cardiomyocytes in response to pathological stimuli.
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Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Fibrose / Proteínas Serina-Treonina Quinases / Cardiomegalia / Coração Limite: Animais Idioma: Inglês Revista: FASEB J Assunto da revista: Biologia / Fisiologia Ano de publicação: 2006 Tipo de documento: Artigo País de afiliação: Estados Unidos