Gene Remodeling in Type 2 Diabetic Cardiomyopathy and Its Phenotypic Rescue with SERCA2a 英文参考文献.docVIP

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Gene Remodeling in Type 2 Diabetic Cardiomyopathy and Its Phenotypic Rescue with SERCA2a 英文参考文献.doc

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Gene Remodeling in Type 2 Diabetic Cardiomyopathy and Its Phenotypic Rescue with SERCA2a 英文参考文献

GeneRemodelinginType2DiabeticCardiomyopathy andItsPhenotypicRescuewithSERCA2a IoannisKarakikes1.,MaengjoKim1.,LahouariaHadri1,SusumuSakata3,YezhouSun2,WeijiaZhang2, ElieR.Chemaly1,RogerJ.Hajjar1,DjamelLebeche1* 1CardiovascularResearchCenter,MountSinaiSchoolofMedicine,NewYork,NewYork,UnitedStatesofAmerica,2BioinformaticsLaboratoryofPersonalizedMedicine ResearchProgram,MountSinaiSchoolofMedicine,NewYork,NewYork,UnitedStatesofAmerica, 3DepartmentofPhysiologyII,NaraMedicalUniversity,Kashihara, Nara,Japan Abstract Background/Aim:Diabetes-associatedmyocardialdysfunctionresultsinalteredgeneexpressionintheheart.Weaimedto investigatethechangesingeneexpressionprofiles accompanyingdiabetes-inducedcardiomyopathyanditsphenotypic rescuebyrestorationofSERCA2aexpression. Methods/Results: Using the Otsuka Long-Evans Tokushima Fatty rat model of type 2 diabetes and the Agilent rat microarray chip, we analyzed gene expression by comparing differential transcriptional changes in age-matched control versusdiabeticheartsanddiabeticheartsthatreceivedgenetransferofSERCA2a.Microarrayexpressionprofilesofselected genes were verified with real-time qPCR and immunoblotting. Our analysis indicates that diabetic cardiomyopathy is associatedwithadownregulationoftranscripts.DiabeticcardiomyopathicheartshavereducedlevelsofSERCA2a.SERCA2a genetransferintheseheartsreduceddiabetes-associatedhypertrophy,anddifferentiallymodulatedtheexpressionof76 genes and reversed the transcriptional profile induced by diabetes. In isolated cardiomyocytes in vitro , SERCA2a overexpressionsignificantlymodifiedtheexpressionofanumberoftranscriptsknowntobeinvolvedininsulinsignaling, glucosemetabolismandcardiacremodeling. Conclusion:Thisinvestigationprovidedinsightintothepathophysiologyofcardiacremodelingandthepotentialroleof SERCA2anormalizationinmultiplepathwaysindiabeticcardiomyopathy. Citation: Karakikes I, Kim M, Hadri L, Sakata S, Sun Y, et al. (2009) Gene Remodeling in Type 2 Diabetic Cardiomyopathy and