动脉硬化图象PPT课件.ppt

,.,.,.,PLAQUEPROGRESSION4Inflammatorymoleculescanpromotefurthergrowthoftheplaqueandformationofafibrouscapoverthelipidcore.Thecapdevelopswhenthemoleculesinducesmoothmusclecellsofthemediatomigratetothetopoftheintima,multiplyandproduceatough,fibrousmatrixthatgluesthecellstogether.Thecapaddstothesizeoftheplaquebutalsowallsitoffsafelyfromtheblood.,.,PLAQUERUPTURE5Later,inflammatorysubstancessecretedbyfoamcellscandangerouslyweakenthecapbydigestingmatrixmoleculesanddamagingsmoothmusclecells,whichthenfailtorepairthecap.Meanwhilethefoamcellsmaydisplaytissuefactor,apotentclotpromoter.Iftheweakenedplaqueruptures,tissuefactorwillinteractwithclot-promotingelementsintheblood,causingathrombus,orclot,toform.Iftheclotisbigenough,itwillhalttheflowofbloodtotheheart,producingaheartattackthedeathofcardiactissue.FibrouscapMigratingsmoothmusclecell,.,.,.,.,.,.,正常动脉结构,.,冠脉病变进展,.,冠脉狭窄和阻塞,.,损伤反应学说,.,运动试验心电图,.,运动试验,.,动脉硬化分期,.,血管内皮细胞,.,免疫组化检测oxLDL,.,白细胞积聚,.,.,为何分叉处病变多发,.,3岁男孩的冠状动脉脂质条纹,.,SmoothMuscleCellMigrationandProliferation,.,动脉粥样硬化呈阶梯式发展,.,FIGURE308.Mechanismsofplaquedisruption,.,TheArterialExtracellularMatrix,AngiogenesisinPlaquesPlaqueMineralization,.,COMPLICATIONSOFATHEROSCLEROSIS,ArterialStenosesandTheirClinicalImplications,.,PlaqueRuptureandThrombosis,Afibrofattyeccentriccoronaryatheroscleroticplaquewithruptureofitsthin,delicatefibrouscap(arrows),exposureofthenecroticlipidcore(NLC)tothebloodstream,andsubsequentluminalthrombosisprecipitatinganacuteischemicepisode,.,aorticcomplicatedatheromatouslesion,Grossphotographsillustrateanaorticcomplicatedatheromatouslesionwithruptureofitsfibrouscap(FC).,lipidcore(LC)M=media;T=thrombus,.,Rupturedaorticatheroscleroticplaques,Additionalexamplesofrupturedaorticatheroscleroticplaqueswithexposureoftheirlipidcores(LC)tobloodelementsandsubsequentthrombosis.A,Therupturedendsofthefibrouscap(FC),.,粥样硬化形成中细胞外间质和内膜炎症的关系,Aschematicrelatingextracellularmatrixmetabolismtointimalinflammationduringatherogenesis,TNF-a=tumornecrosisfactor-alpha;M-CSF=macrophagecolonystimulatingfactor;MCP-1=monocytechemoattractantprotein-1.,.,外膜,lipidcore,脂核,不稳定性冠心病,血小板聚积在破裂/浸润的部位,.,外膜,lipidcore,脂核,血栓,不稳定性冠心病,血栓形成并扩展进入管腔及斑块,纤维胶原合成减少，分解增多纤维帽中平滑肌细胞少脂核大，巨嗜细胞含量多,.,ThrombosisDuetoSuperficialErosionoflaques,Superficialerosionofexperimentalatheroscleroticlesionsshownbyscanningelectronmicroscopy.A,Inthelow-powerview,therentinendotheliumisevident.Leukocyteshaveadheredtothesubendothelium,whichisbeginningtobecoveredwithacarpetofplatelets.B,Thehigh-powerviewshowsafieldselectedfromthecenterofAthatshowstheleukocytesandplateletsadherenttothesubendothelium.,.,Plateletthrombuscomplicatingaplaquedisruptioninexperimentalatherosclerosis,Thistransmissionelectronmicrographshowsacrosssectionofmacrophagestuddedwithplateletsthathaveclumpedtoformamicroscopicthrombus.,.,SPECIALCASESOFARTERIOSCLEROSIS,RestenosisafterArterialIntervention,.,Comparisonofusualatherosclerosisandtransplantationarteriosclerosis,.,Amultifactorialviewofthepathogenesisofatherosclerosis,.,RiskFactorsforAtheroscleroticDisease,.,DYSLIPIDEMIA,.,Structureoflipoproteins,.,Structureoflipoproteins,Theoil-dropormixedmicellemodeloflipoproteinstructureforchylomicron,verylow-densitylipoprotein(VLDL),low-densitylipoprotein(LDL),andhigh-densitylipoprotein(HDL).,.,Relativesizeofplasmalipoproteinsaccordingtotheirhydrateddensity.,.,TABLE312.APOLIPOPROTEINS,.,Cellularcholesterolhomeostasisinvarioustissues,.,Schematicdiagramofthelipidtransportsystem,Apo=apolipoprotein;LPL=lipoproteinlipase;HL=hepaticlipase;CETP=cholesterylestertransferprotein;LCAT=lecithincholesterolacyltransferase;FFA=freefattyacids;,.,Lipoprotein(a)Lp(a),Lipoprotein(a)Lp(a)representsadistinctgeneticformofLDLwhereinapolipoprotein(a)apo(a)islinkedtoapoB100viacysteineK436ofapo(a)andanunknowncysteinefromthecarboxylendofapoBbydisulfidelinkage,.,ManagementofLipoproteinDisorders,.,ManagementofLipoproteinDisorders,GENERALAPPROACHES.SPECIFICTREATMENTS,RESINS.HMGCoAREDUCTASEINHIBITORS(STATINS).FIBRICACIDDERIVATIVES(FIBRATES).NICOTINICACID(NIACIN).FISHOILS.MONITORING.OTHERMEDICATIONS.DIETARYSUPPLEMENTS(“NUTRACEUTICALS”).AGGRESSIVEMEASURESFORTREATINGREFRACTORYELEVATIONOFLDL.GENETHERAPY:AFUTUREAPPROACHTODYSLIPIDEMIA?,.,饮食控制,Correlationbetweenincreasingdietaryfatandserumcholesterolinpopulationsmigratingtocountrieswithdifferentdietaryhabits.,.,Proposedmechanismbywhichdietarysaturatedfattyacidsraiseserumcholesterol,AmechanismbywhichdietarysaturatedfattyacidselevatetheLDLcholesterollevelappearstobedown-regulationoftheexpressionofhepaticLDLreceptors.DietarysaturatedfattyacidshavebeenshowntoinhibitLDLreceptoractivity,althoughtheirmechanismofactionisunclear.,.,Thepopulation-basedapproachtocholesterolloweringbydiet,.,Mechanismofactionofstatins,Thestatinsinhibittherate-limitingenzyme,hydroxymethylglutaryl-coenzymeA(HMG-CoA)reductase,incholesterolbiosynthesis(1).Themajororgansforcholesterolbiosynthesisarethesmallintestineandliver.TheassociateddecreaseinhepaticandcellularcholesterolconcentrationstimulatestheproductionofLDLreceptors,whichincreasetherateofremovalofLDLfromtheplasma(2).ThereisalsoincreasedremovalofVLDLremnantsandintermediate-densitylipoprotein(IDL),whichareprecursorstoLDLformation.Insomepatients,theremayalsobeadecreaseinlipoproteinsynthesis(3).TheenhancedremovalofVLDLremnantsandIDLandtheinhibitionoflipoproteinsynthesismaycontributetothemodesttriglyceride-loweringeffectofthestatins.Acetyl-CoA=acetylcoenzymeA;HTGL=hepatictriglyceridelipase.,.,SMOKING,.,Riskofsmoking,Relativerisksofdeathduetocoronaryarterydisease(top)andstroke(bottom)accordingtolevelofdailycigaretteconsumption,Smokingcessationalonereducestheriskofafirstheartattackbynea