急性心肌梗死信号转导图

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