Targeting focal adhesion kinase with small interfering RNA prevents and reverses load-induced cardiac hypertrophy in mice

dc.creatorClemente, CFMZ
dc.creatorTornatore, TF
dc.creatorTheizen, TH
dc.creatorDeckmann, AC
dc.creatorPereira, TC
dc.creatorLopes-Cendes, I
dc.creatorSouza, JRM
dc.creatorFranchini, KG
dc.date2007
dc.dateDEC 7
dc.date2014-11-15T10:00:50Z
dc.date2015-11-26T17:19:22Z
dc.date2014-11-15T10:00:50Z
dc.date2015-11-26T17:19:22Z
dc.date.accessioned2018-03-29T00:07:03Z
dc.date.available2018-03-29T00:07:03Z
dc.identifierCirculation Research. Lippincott Williams & Wilkins, v. 101, n. 12, n. 1339, n. 1348, 2007.
dc.identifier0009-7330
dc.identifierWOS:000251445500017
dc.identifier10.1161/CIRCRESAHA.107.160978
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/79048
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/79048
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/79048
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1282890
dc.descriptionHypertrophy is a critical event in the onset of failure in chronically overloaded hearts. Focal adhesion kinase (FAK) has attracted particular attention as a mediator of hypertrophy induced by increased load. Here, we demonstrate increased expression and phosphorylation of FAK in the hypertrophic left ventricles (LVs) of aortic-banded mice. We used an RNA interference strategy to examine whether FAK signaling plays a role in the pathophysiology of load-induced LV hypertrophy and failure. Intrajugular delivery of specific small interfering RNA induced prolonged FAK silencing (approximate to 70%) in both normal and hypertrophic LVs. Myocardial FAK silencing was accompanied by prevention, as well as reversal, of load-induced left ventricular hypertrophy. The function of LVs was preserved and the survival rate was higher in banded mice treated with small interfering RNA targeted to FAK, despite the persistent pressure overload. Studies in cardiac myocytes and fibroblasts harvested from LVs confirmed the ability of the systemically administered specific small interfering RNA to silence FAK in both cell types. Further analysis indicated attenuation of cardiac myocyte hypertrophic growth and of the rise in the expression of beta-myosin heavy chain in overloaded LVs. Moreover, FAK silencing was demonstrated to attenuate the rise in the fibrosis, collagen content, and activity of matrix metalloproteinase-2 in overloaded LVs, as well as the rise of matrix metalloproteinase-2 protein expression in fibroblasts harvested from overloaded LVs. This study provides novel evidence that FAK may be involved in multiple aspects of the pathophysiology of cardiac hypertrophy and failure induced by pressure overload.
dc.descriptionO TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE FEVEREIRO DE 2015.
dc.description101
dc.description12
dc.description1339
dc.description1348
dc.languageen
dc.publisherLippincott Williams & Wilkins
dc.publisherPhiladelphia
dc.publisherEUA
dc.relationCirculation Research
dc.relationCirc.Res.
dc.rightsembargo
dc.sourceWeb of Science
dc.subjectcardiac myocytes
dc.subjectsignaling
dc.subjectmechanical stress
dc.subjectheart failure
dc.subjectFas Protects Mice
dc.subjectHeart-failure
dc.subjectVentricular Hypertrophy
dc.subjectMyocyte Hypertrophy
dc.subjectActivation
dc.subjectExpression
dc.subjectOverload
dc.subjectStretch
dc.subjectSirnas
dc.subjectPhosphorylation
dc.titleTargeting focal adhesion kinase with small interfering RNA prevents and reverses load-induced cardiac hypertrophy in mice
dc.typeArtículos de revistas


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