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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorGUIDO, Maria C.
dc.contributor.authorCLEMENTE, Carolina F.
dc.contributor.authorMORETTI, Ana I.
dc.contributor.authorBARBEIRO, Hermes V.
dc.contributor.authorDEBBAS, Victor
dc.contributor.authorCALDINI, Elia G.
dc.contributor.authorFRANCHINI, Kleber G.
dc.contributor.authorSORIANO, Francisco G.
dc.date.accessioned2013-07-30T15:15:07Z
dc.date.available2013-07-30T15:15:07Z
dc.date.issued2012
dc.description.abstractSepsis 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.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo Research Foundation) [06/00443-6]
dc.identifier.citationSHOCK, v.37, n.1, p.77-84, 2012
dc.identifier.doi10.1097/SHK.0b013e31823532ec
dc.identifier.issn1073-2322
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1014
dc.language.isoeng
dc.publisherLIPPINCOTT WILLIAMS & WILKINS
dc.relation.ispartofShock
dc.rightsrestrictedAccess
dc.rights.holderCopyright LIPPINCOTT WILLIAMS & WILKINS
dc.subjectFocal adhesion protein-tyrosine kinases
dc.subjectcytokines
dc.subjectinflammation
dc.subjectsepsis
dc.subjectshock septic
dc.subject.otherhuman septic shock
dc.subject.othersevere sepsis
dc.subject.otherventricular dysfunction
dc.subject.otherlung injury
dc.subject.othermice
dc.subject.otherhypertrophy
dc.subject.otherheart
dc.subject.otherpathogenesis
dc.subject.otheractivation
dc.subject.otherresponses
dc.subject.wosCritical Care Medicine
dc.subject.wosHematology
dc.subject.wosSurgery
dc.subject.wosPeripheral Vascular Disease
dc.titleSMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalCLEMENTE, Carolina F.:Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, Campinas, SP, Brazil
hcfmusp.author.externalFRANCHINI, Kleber G.:Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, Campinas, SP, Brazil
hcfmusp.citation.scopus10
hcfmusp.contributor.author-fmusphcMARIA CAROLINA GUIDO
hcfmusp.contributor.author-fmusphcANA IOCHABEL SOARES MORETTI
hcfmusp.contributor.author-fmusphcHERMES VIEIRA BARBEIRO
hcfmusp.contributor.author-fmusphcVICTOR DEBBAS
hcfmusp.contributor.author-fmusphcELIA TAMASO ESPIN GARCIA CALZOLARI
hcfmusp.contributor.author-fmusphcFRANCISCO GARCIA SORIANO
hcfmusp.description.beginpage77
hcfmusp.description.endpage84
hcfmusp.description.issue1
hcfmusp.description.volume37
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed21921830
hcfmusp.origem.scopus2-s2.0-83655191975
hcfmusp.origem.wosWOS:000298884900012
hcfmusp.publisher.cityPHILADELPHIA
hcfmusp.publisher.countryUSA
hcfmusp.relation.referenceAoyama T, 2010, GASTROENTEROL RES PR
hcfmusp.relation.referenceBarbeiro DF, 2011, IMMUNOBIOLOGY, V216, P302, DOI 10.1016/j.imbio.2010.08.002
hcfmusp.relation.referenceBergman MR, 2007, AM J PHYSIOL-HEART C, V292, pH1847, DOI 10.1152/ajpheart.00434.2006
hcfmusp.relation.referenceCazita PM, 2008, SHOCK, V30, P590, DOI 10.1097/SHK.0b013e31816e30fd
hcfmusp.relation.referenceCinel I, 2007, CURR OPIN INFECT DIS, V20, P345, DOI 10.1097/QCO.0b013e32818be70a
hcfmusp.relation.referenceClemente CFMZ, 2007, CIRC RES, V101, P1339, DOI 10.1161/CIRCRESAHA.107.160978
hcfmusp.relation.referenceDykxhoorn DM, 2006, CELL, V126, P231, DOI 10.1016/j.cell.2006.07.007
hcfmusp.relation.referenceEble DM, 2000, AM J PHYSIOL-HEART C, V278, pH1695
hcfmusp.relation.referenceFALLACH R, 2011, J MOL CELL CARDIOL, V48, P1236
hcfmusp.relation.referenceGuido MC, 2007, CLIN EXP PHARMACOL P, V34, P1165, DOI 10.1111/j.1440-1681.2007.04689.x
hcfmusp.relation.referenceHamar P, 2004, P NATL ACAD SCI USA, V101, P14883, DOI 10.1073/pnas.040621101
hcfmusp.relation.referenceHe ZY, 2009, J RECEPT SIG TRANSD, V29, P119, DOI 10.1080/10799890902845690
hcfmusp.relation.referenceHutchinson KR, 2010, J MOL CELL CARDIOL, V48, P564, DOI 10.1016/j.yjmcc.2009.06.001
hcfmusp.relation.referenceJones AE, 2009, CRIT CARE CLIN, V25, P769, DOI 10.1016/j.ccc.2009.06.003
hcfmusp.relation.referenceKATZ AM, 1994, ANN INTERN MED, V121, P363
hcfmusp.relation.referenceKluwe J, 2009, J MOL MED-JMM, V87, P125, DOI 10.1007/s00109-008-0426-z
hcfmusp.relation.referenceGaddnas F, 2009, CRIT CARE, V13, DOI 10.1186/cc7780
hcfmusp.relation.referenceLORIGADOS CB, 2011, ENDOCR METAB IMMUNE, V10, P274
hcfmusp.relation.referenceMELO ES, 2011, IMMUNOBIOLOGY, V215, P435
hcfmusp.relation.referenceMELO ES, 2011, MOL IMMUNOL, V47, P2587
hcfmusp.relation.referenceNadruz W, 2005, CARDIOVASC RES, V68, P87, DOI 10.1016/j.cardiores.2005.05.011
hcfmusp.relation.referenceNATANSON C, 1989, J EXP MED, V169, P823, DOI 10.1084/jem.169.3.823
hcfmusp.relation.referenceNegri EM, 2000, HISTOPATHOLOGY, V37, P393, DOI 10.1046/j.1365-2559.2000.00992.x
hcfmusp.relation.referenceNogueira AC, 2008, SHOCK, V29, P342
hcfmusp.relation.referenceOtte JM, 2003, GASTROENTEROLOGY, V124, P1866, DOI 10.1016/S0016-5085(03)00403-7
hcfmusp.relation.referencePARKER MM, 1990, CHEST, V97, P126, DOI 10.1378/chest.97.1.126
hcfmusp.relation.referenceRojas M, 2005, AM J PHYSIOL-LUNG C, V288, pL333, DOI 10.1152/ajplung.00334.2004
hcfmusp.relation.referenceSALDIVA PHN, 1989, CHEST, V95, P953, DOI 10.1378/chest.95.5.953
hcfmusp.relation.referenceSeki E, 2007, NAT MED, V13, P1324, DOI 10.1038/nm1663
hcfmusp.relation.referenceSorensen DR, 2003, J MOL BIOL, V327, P761, DOI 10.1016/S0022-2836(03)00181-5
hcfmusp.relation.referenceSoriano FG, 2006, CRIT CARE MED, V34, P1073, DOI 10.1097/01.CCM.0000206470.47721.8D
hcfmusp.relation.referenceSoriano FG, 2002, SHOCK, V17, P286, DOI 10.1097/00024382-200204000-00008
hcfmusp.relation.referenceTaylor JM, 2000, J BIOL CHEM, V275, P19250, DOI 10.1074/jbc.M909099199
hcfmusp.relation.referenceVincent JL, 2002, CLIN INFECT DIS, V34, P1084, DOI 10.1086/339549
hcfmusp.relation.referenceZanotti-Cavazzoni SL, 2009, CURR OPIN CRIT CARE, V15, P392, DOI 10.1097/MCC.0b013e3283307a4e
hcfmusp.relation.referenceZeisel MB, 2005, J IMMUNOL, V174, P7393
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.scopus.lastupdate2024-05-17
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