MEF2C Silencing Attenuates Load-Induced Left Ventricular Hypertrophy by Modulating mTOR/S6K Pathway in Mice

Autor(es):Mostrar menos -

Pereira, Ana Helena M. ^[1] ; Clemente, Carolina F. M. Z. ^[1] ; Cardoso, Alisson C. ^[1] ; Theizen, Thais H. ^[1] ; Rocco, Silvana A. ^[1] ; Judice, Carla C. ^[1] ; Guido, Maria Carolina ^[1] ; Pascoal, Vinicius D. B. ^[2] ; Lopes-Cendes, Iscia ^[2] ; Souza, Jose Roberto M. ^[1] ; Franchini, Kleber G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Internal Med, Sch Med, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Dept Med Genet, Sch Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 4, n. 12, p. e8472, 2009.
• Citações Web of Science: 22

Resumo

Background: The activation of the members of the myocyte enhancer factor-2 family (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and failure. However, the role of its individual components in the pathogenesis of cardiac hypertrophy remains unclear. Methodology/Principal Findings: In this study, we investigated whether MEF2C plays a role in mediating the left ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial MEF2C induced by specific small interfering RNA (siRNA) has been shown to attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic banded mice. We detected that the depletion of MEF2C also results in lowered levels of both PGC-1 alpha and mitochondrial DNA in the overloaded left ventricle, associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload. Treatment with the amino acid leucine stimulated S6K and suppressed the attenuation of left ventricular hypertrophy and fibrosis in the aforementioned aortic banded mice. Conclusion/Significance: These findings represent new evidences that MEF2C depletion attenuates the hypertrophic responses to mechanical stress and highlight the potential of MEF2C to be a target for new therapies to cardiac hypertrophy and failure. (AU)

• Processo FAPESP: 08/53519-5 - Caracterizacao topologica e funcional da interacao entre a tirosina quinase fak e o fator de transcricao mef2.
• Beneficiário: Alisson Campos Cardoso
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 06/54878-3 - Patogênese da hipertrofia e insuficiência cardíacas: mecanismos ativados por estimulo mecânico
• Beneficiário: Kleber Gomes Franchini
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/53583-5 - Efeito do silenciamento genico do fator de transcricao mef2c na hipertrofia e insuficiencia cardiaca induzida por sobrecarga pressorica cronica.
• Beneficiário: Ana Helena Macedo Pereira
• Modalidade de apoio: Bolsas no Brasil - Doutorado