Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation英文文献资料.docVIP

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Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation英文文献资料.doc

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Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation英文文献资料

HindawiPublishingCorporation InternationalJournalofVascularMedicine Volume2012,ArticleID159646,6pages doi:10.1155/2012/159646 ResearchArticle BradykininType-2ReceptorExpressionCorrelateswithAgeand IsSubjectedtoTranscriptionalRegulation InkaLiesmaa, 1 NaotakaShiota, 1JormaO.Kokkonen, 1,2 andKenA.Lindstedt 1 PetriT.Kovanen, 1 1 2 WihuriResearchInstitute,Kalliolinnantie4,00140Helsinki,Finland DepartmentofCardiology,Jyv¨askyl¨aCentralHospital,40620Jyv¨askyl¨a,Finland CorrespondenceshouldbeaddressedtoInkaLiesmaa,inka.liesmaa@kolumbus.? Received19May2011;Accepted11July2011 AcademicEditor:JohnW.Calvert Copyright?2012InkaLiesmaaetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Accumulatingworkinexperimentalanimalssuggeststhatbradykinin(BK)exertscardioprotectivee?ectsviabradykinintype-2 receptors(BK-2Rs).Inhumanend-stageheartfailure,BK-2Rsaresigni?cantlydownregulatedbymechanismsthathaveremained elusive.Hearttissuesfromidiopathicdilatedcardiomyopathy(IDC;n = 7),coronaryheartdisease(CHD;n = 6),andnormal patients(n=6)wereanalyzedbyRT-PCR,SSCP,andWesternblotting.InnormalandIDChearts,BK-2Rexpressionincreased with age, with a lower relative increase in IDC hearts. BK-2RmRNAand protein levels showed a positivelinear correlation, suggestingtranscriptionalregulation.TwoknownBK-2Rpromoterpolymorphisms,?58T/Cand?9/+9,werefoundtobepresent inthestudypopulation.TheallelicfrequenciesfortheC-allelein?58T/Cwere0.58innormalandCHDheartsand0.81inIDC hearts.Furthermore,theallelicfrequenciesforthe?9and+9alleleswere0.42and0.58innormalheartsand0.64and0.36inIDC hearts,respectively.AllanalyzedCHDheartswerehomozygousforthe?9allele.Thus,theexpressionofcardioprotectiveBK-2Rs inhumanheartsisincreasedwithageinnormalandIDCheartsandmayberegulatedonthetranscriptionallevel.Moreover, comparisonofnormalsubjectsandpatientswithfailingheartsrevealeddi?erentallelicfre