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

dc.creatorPereira, AHM
dc.creatorClemente, CFMZ
dc.creatorCardoso, AC
dc.creatorTheizen, TH
dc.creatorRocco, SA
dc.creatorJudice, CC
dc.creatorGuido, MC
dc.creatorPascoal, VDB
dc.creatorLopes-Cendes, I
dc.creatorSouza, JRM
dc.creatorFranchini, KG
dc.date2009
dc.dateDEC 29
dc.date2014-07-30T13:40:58Z
dc.date2015-11-26T16:41:47Z
dc.date2014-07-30T13:40:58Z
dc.date2015-11-26T16:41:47Z
dc.date.accessioned2018-03-28T23:26:05Z
dc.date.available2018-03-28T23:26:05Z
dc.identifierPlos One. Public Library Science, v. 4, n. 12, 2009.
dc.identifier1932-6203
dc.identifierWOS:000273105200008
dc.identifier10.1371/journal.pone.0008472
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/53560
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/53560
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1273042
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBackground: 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.
dc.description4
dc.description12
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionLaboratorio Cristalia
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFAPESP [2006/54878-3, 2008/53583-5, 2008/53519-5]
dc.descriptionCNPq [305604/2006-6, 501160/2008-6]
dc.languageen
dc.publisherPublic Library Science
dc.publisherSan Francisco
dc.publisherEUA
dc.relationPlos One
dc.relationPLoS One
dc.rightsaberto
dc.sourceWeb of Science
dc.subjectFocal Adhesion Kinase
dc.subjectInduced Cardiac-hypertrophy
dc.subjectMyocyte Enhancer Factor-2
dc.subjectMitochondrial Biogenesis
dc.subjectTranscription Factor
dc.subjectHeart-failure
dc.subjectGenetic Program
dc.subjectC-jun
dc.subjectExpression
dc.subjectCardiomyopathy
dc.titleMEF2C Silencing Attenuates Load-Induced Left Ventricular Hypertrophy by Modulating mTOR/S6K Pathway in Mice
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución