Differences in MEF2 and NFAT Transcriptional Pathways According to Human Heart Failure Aetiology 英文参考文献.docVIP

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Differences in MEF2 and NFAT Transcriptional Pathways According to Human Heart Failure Aetiology 英文参考文献.doc

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Differences in MEF2 and NFAT Transcriptional Pathways According to Human Heart Failure Aetiology 英文参考文献

DifferencesinMEF2andNFATTranscriptionalPathways AccordingtoHumanHeartFailureAetiology RaquelCorte′s1.,MiguelRivera1,EstherRosello′-Llet?′1.,LuisMart?′nez-Dolz2,LuisAlmenar2, InmaculadaAzor?′n3,FranciscaLago4,Jose′ Ramo′nGonza′lez-Juanatey4,ManuelPortole′s5* 1Cardiocirculatory Unit, Research Center, Hospital Universitario La Fe, Valencia, Spain, 2Cardiology Unit, Hospital Universitario La Fe, Valencia, Spain, 3Experimental Neurology,ResearchCenter,HospitalUniversitarioLaFe,Valencia,Spain,4MolecularandCellularCardiologyUnit,InstituteofBiomedicalResearch,andDepartmentof Cardiology,HospitalCl?′nicoUniversitario,SantiagodeCompostela,Spain,5CellBiologyandPathologyUnit,ResearchCenter,HospitalUniversitarioLaFe,Valencia,Spain Abstract Background:Ca2+handlingmachinerymodulatestheactivationofcardiactranscriptionpathwaysinvolvedinheartfailure (HF).ThepresentstudyinvestigatedtheeffectofHFaetiologyonCa handlingproteinsandNFAT1,MEF2CandGATA4 (transcriptionfactors)inthesamecardiactissue. +2 MethodologyandPrincipalFindings:Atotalof83heartsfromischemic(ICM,n=43)anddilated(DCM,n=31)patients undergoinghearttransplantationandcontrols(CNT,n=9)wereanalyzedbywesternblotting.Subcellulardistributionwas analyzedbyfluorescenceandelectronmicroscopy.WhenwecomparedCa+2handlingproteinsaccordingtoHFaetiology, 2+ ICMshowedhigherlevelsofcalmodulin(24%,p,0.01),calcineurin(26%,p,0.01)andCa /Calmodulin-dependentkinaseII (CaMKIIdb nuclear isoform 62%, p,0.001) than the CNT group. However, these proteins in DCM did not significantly increase.Furthermore,ICMshowedasignificantelevationinMEF2C(33%,p,0.01),andGATA4(49%,p,0.05);alsoNFAT1 (66%, p,0.001) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These resultsweresupportedbyfluorescenceandelectronmicroscopyanalysis.Whereas,DCMonlyhadasignificantincreasein GATA4(52%,p,0.05).CorrelationsbetweenNFAT1andMEF2Cinbothgroups(ICMr=0.38andDCMr=0.59,p,0.05and p,0.01,respectively)werefound;onlyICMshow