Increased expression and phosphorylation of focal adhesion kinase correlates with dysfunction in the volume-overloaded human heart

Autor(es)

Lopes‚ M. ; Ribeiro‚ G. ; Tornatore‚ T. ; Clemente‚ C. ; Teixeira‚ V. ; Franchini‚ K.

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 113, n. 3/4, p. 195-204, Aug. 2007.
• Área do conhecimento: Ciências da Saúde - Medicina
• Assunto(s): Sistema cardiovascular Miocárdio Insuficiência cardíaca Hipertrofia Miócitos cardíacos Transdução de sinais Colágenos fibrilares Proteína-tirosina quinases de adesão focal

Resumo

FAK (focal adhesion kinase) has been shown to mediate the hypertrophic growth of the left ventricle. Experimental results also suggest that FAK may contribute to the structural and functional deterioration of the chronically overloaded left ventricle. In the present study, we postulated that FAK expression and phosphorylation may be altered in the volume-overloaded heart in humans. FAK expression and phosphorylation at Tyr397 were detected by Western blotting and immunohistochemistry in samples from endomyocardial biopsies from patients with MR (mitral regurgitation; n=21) and donor subjects (n=4). Hearts from patients with MR had degenerated cardiac myocytes and areas of fibrosis. In this group, the myocardial collagen area was increased (18% in MR hearts compared with 3% in donor hearts respectively) and correlated negatively with left ventricular ejection fraction (r=-0.74; P>0.001). FAK expression and phosphorylation at Tyr397 (a marker of the enzyme activity) were increased in samples from MR hearts compared with those from donor hearts (3.1- and 4.9-fold respectively). In myocardial samples from donor hearts, anti-FAK staining was almost exclusively restricted to cardiac myocytes; however, in myocardial samples from MR hearts, staining with the anti-FAK antibody was found to occur in myocytes and the interstitium. There was a positive correlation between collagen and the interstitial areas stained with the anti-FAK antibody (r=0.76; P>0.001). Anti-FAK and anti-vimentin staining of the interstitial areas of samples from MR hearts were extensively superimposed, indicating that most of the interstitial FAK was located in fibroblasts. In conclusion, FAK expression and phosphorylation are increased and may contribute to the underlying structural and functional abnormalities in the volume-overloaded heart in humans. (AU)

• Processo FAPESP: 01/11698-1 - Mecanismos de sinalização celular ativados por sobrecarga mecânica: implicações na hipertrofia e remodelamento miocárdicos
• Beneficiário: Kleber Gomes Franchini
• Modalidade de apoio: Auxílio à Pesquisa - Temático