更新时间:2011-01-05 18:02:13
急性心肌梗死信号转导图信息来源:本站原创http://www.bioon.com生物谷网站Myocardialinfraction(MI)istheconditionofirreversiblenecrosisoftheheartmusclethatresultsfromprolongedischemia.Nearly1.5millionpeopleinUSsustainanMIeachyear,andthiseventprovesfatalinapproximatelyonethirdofpatients.Approximately90%ofMIresultfromformationofanacutethrombusthatobstructsanatheroscleroticcoronaryartery.Thethrombustransformsaregionofplaquenarrowingtooneofcompletevesselocclusion(toprightinpink).Theresponsiblethrombusappearstobegeneratedbyinteractionsbetweentheatheroscleroticplaque,thecoronaryendothelium,circulatingplatelets,anddynamicvasomotortoneofthevesselwall,allofwhichoverwhelmnaturalprotectivemechanisms.Theendogenousprotectivemechanismsagainstthrombosisinclude:1.InactivationofthrombinbyantithrombinIII(ATIII),theeffectivenessofwhichisenhancedbybindingofATIIItoheparinsulafate.Theantithrombinbindingregionofcommercialheparinconsistsofsulfateddisaccharideunits(bottompanel).2.InactivationofclottingfactorsVaandVIIIabyactivatedproteinC(proteinC*),anactionthatisenhancedbyproteinS.ProteinCisactivatedbythethrombomodulin(TM)-thrombincomplex.3.InactivationoffactorVII/tissuefactorcomplexbytissuefactorpathwayinhibitor(TFPI).Coumarindrugs(Warfarin)blockstheg-carboxylationofGluresiduesinprothrombinandfactorsVII,IXandXwhichresultsinincompletemoleculesthatarebiologicallyinactiveincoagulation(leftpanel).4.Lysisoffibrinclotsbytissueplasminogenactivator(tPA).5.InhibitionofplateletactivationbyprostacyclinandEDRF-NO.Plateletsadheretoexposedcollagenandareactivatedatthesiteofendothelialdamageinthebloodvessel.Activatedplateletsreleaseadenosinediphosphate(ADP),serotonin(5-HT),andthromboxaneA2(TXA2),whichactivateadditionalplatelets.Bindingofthrombinfurtheractivatestheplatelets.Threeadjoiningplateletsareshownintheprocessofviscousmetamorphosis(topright).IncreasedcellularCa2+facilitatesbindingoffibrinogen.Iftheintraluminalthrombusatthesiteofplaquedisruptiontotallyoccludesthevessel,bloodflowbeyondtheobstructionwillcease,prolongedischemiawilloccurandMI(usuallyQ-waveMI)willlikelyresult(seeelectrocardiogramonthetopleft).AcuteMiocardialInfraction(Ch7inPathophysiologyofHeartDisease2ndeditionbyLeonardS.Lilly)pp.145-169BloodCoagulationinCardiovascularDisease(Ch23inMolecularBasisofcardiovascularDisease.ACompaniontoBraunwaldsHeartDiseaseed.byKennethRChien)pp.505-535DrugsUsedinDisordersofCoagulation(Ch33inBasicandClinicalPharmacology6theditionbyBertramGKatzung)pp.507-521