SMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA

dc.creatorGuido, Maria C.
dc.creatorClemente, Carolina F.
dc.creatorMoretti, Ana I.
dc.creatorBarbeiro, Hermes V.
dc.creatorDebbas, Victor
dc.creatorCaldini, Elia G.
dc.creatorFranchini, Kleber G.
dc.creatorSoriano, Francisco G.
dc.date2012
dc.date2013-09-19T18:05:51Z
dc.date2016-07-01T15:17:33Z
dc.date2013-09-19T18:05:51Z
dc.date2016-07-01T15:17:33Z
dc.date.accessioned2018-03-29T01:55:38Z
dc.date.available2018-03-29T01:55:38Z
dc.identifierShock. Lippincott Williams & Wilkins, v.37, n.1, p.77-84, 2012
dc.identifier1073-2322
dc.identifierWOS:000298884900012
dc.identifier10.1097/SHK.0b013e31823532ec
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/1792
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/1792
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1308849
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionSepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.
dc.description37
dc.description1
dc.description77
dc.description84
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageeng
dc.publisherLippincott Williams & Wilkins
dc.publisherPhiladelphia
dc.relationShock
dc.rightsfechado
dc.sourceWOS
dc.subjectFocal adhesion protein-tyrosine kinases
dc.subjectcytokines
dc.subjectinflammation
dc.subjectsepsis
dc.subjectshock septic
dc.subjectHUMAN SEPTIC SHOCK
dc.subjectSEVERE SEPSIS
dc.subjectVENTRICULAR DYSFUNCTION
dc.subjectLUNG INJURY
dc.subjectMICE
dc.subjectHYPERTROPHY
dc.subjectHEART
dc.subjectPATHOGENESIS
dc.subjectACTIVATION
dc.subjectRESPONSES
dc.titleSMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA
dc.typeArtículos de revistas


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