血管紧张素转化酶2对于胶原及其限速亚单位p4hα1的作用和机制分析-effect and mechanism analysis of angiotensin converting enzyme 2 on collagen and its rate-limiting subunit p4h1 α 1.docxVIP
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血管紧张素转化酶2对于胶原及其限速亚单位p4hα1的作用和机制分析-effect and mechanism analysis of angiotensin converting enzyme 2 on collagen and its rate-limiting subunit p4h1 α 1
TheroleofACE2forP4Hα1expressionandcollagenproductionAbstractIntroductionCollagenisthemainstructuralproteininextracellularmatrix(ECM),andmainlygeneratedfromvascularsmoothmusclecells(VSMC)whichdistributinginendarterium.Amongallsubtypesofcollagen,typeIandIIIcollagensarethemostcommonsubtypesinvascularwall.AbalanceofcollagenssynthesisanddegradationisthekeyfactorformaintainingECM,enhancingplaquestabilityandreducingrupturevulnerability.Itiswellknownthatprolyl4-hydroxylase(P4H)isthekeyintracellularenzymeofallknowntypesofcollagen,andplaysaveryimportantroleincollagenmetabolism.P4Hisatetramerwithtwoαsubunitsandtwoβsubunits,ofwhich,αsubunitmainlydeterminestheactivityofenzyme.Therefore,P4Hα1,asthecrucialrate-limitingenzyme,iscloselyrelatedtotheproductionofcollagen.OverexpressionofP4Hα1couldincreasecollagenproductionandtheinhibitionofP4Hα1wouldleadtocollagendegradation.Invivorennin-angiotensinsystemplaysacentralroleinthedevelopmentofatherosclerosis.AngiotensinII(AngII)cancausevasoconstriction,VSMCproliferation,hypertrophyandinduceinflammatoryresponse.IthasbeenreportedthatAngIIinhibittheactivityofP4Hα1andthesynthesisofcollagens,promotethedegradationofECM,andfinallyleadtoplaquevulnerabilityandrupture.Onthecontrary,ACE2canconvertAngIItoAng(1-7).Ang(1-7)isaendogenousantagonistfactor,actingonAngIIAT1acceptorandhastheopposeeffecttoAngII.PreviousstudieshavebeenreportedthatAng(1-7)maystimulatevasodilation,antiproliferative,antihypertrophyandanti-inflammatory,thusindicatedAng(1-7)playstheanti-atheroscleroticeffectintheprogressionofatherosclerosis.Uniformly,ourpriorstudiesshowedthatoverexpressionofACE2alsoexertedastrongantiinflammatoryeffectstoincreasecollagenproductionandkeepplaquestability.ObjectiveToinvestigatewhetherACE2enhancestheP4Hα1expressionandcollagenproductioninvitro.ToelucidatethemechanismsofACE2effectsonP4Hα1andcollageninvitro.MethodsPreparationofACE2AdenovirusVectorsTheACE2cDNAwasamplifiedbyRT-PCRfromRNAofmousekidney.Then,recombinantadenovirusescarryingtheACE2(AdACE2)oracontr
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