Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy 英文参考文献.docVIP

SelectiveDecreaseofComponentsoftheCreatineKinase SystemandATPSynthaseComplexinChronicChagas DiseaseCardiomyopathy PriscilaCamilloTeixeira1,2,3,RonaldoHonoratoBarrosSantos4,AlfredoIna′cioFiorelli4 ,Angelina MorandBianchiBilate1,LuizAlbertoBenvenuti5,NoedirAntonioStolf4,JorgeKalil1,2,3,EdecioCunha- Neto1,2,3 * 1Laboratory of Immunology, Heart Institute, School of Medicine, University of Sa?o Paulo, Sa?o Paulo, Brazil, 2Division of Clinical Immunology and Allergy, School of Medicine,UniversityofSa?oPaulo,Sa?oPaulo,Brazil,3InstituteforInvestigationinImmunology(iii),INCT,Sa?oPaulo,Brazil,4DivisionofSurgery,HeartInstitute,Schoolof Medicine,UniversityofSa?o Paulo,Sa?o Paulo,Brazil,5DivisionofPathology,HeartInstitute,SchoolofMedicine,UniversityofSa?o Paulo,Sa?o Paulo,Brazil Abstract Background: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. Methodology/PrincipalFindings:MyocardiumhomogenatesfromCCC(N=5),IC(N=5)andIDC(N=5)patients,aswellas from heart donors (N=5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscularcreatine kinase(CKM) andATPsynthasesubunitsaplhaandbetaby immunoblottingandbyreal-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathygroups.However,totalCKactivity,aswellasATPsynthasealphachainproteinlevels,weresignificantly lowerinCCCsamplesthanICandIDCsamples.CCCmyocardiumdisplayedselectivere