动脉硬化图象PPT课件.ppt

,.,1,.,2,.,3,PLAQUEPROGRESSION4Inflammatorymoleculescanpromotefurthergrowthoftheplaqueandformationofafibrouscapoverthelipidcore.Thecapdevelopswhenthemoleculesinducesmoothmusclecellsofthemediatomigratetothetopoftheintima,multiplyandproduceatough,fibrousmatrixthatgluesthecellstogether.Thecapaddstothesizeoftheplaquebutalsowallsitoffsafelyfromtheblood.,.,4,PLAQUERUPTURE5Later,inflammatorysubstancessecretedbyfoamcellscandangerouslyweakenthecapbydigestingmatrixmoleculesanddamagingsmoothmusclecells,whichthenfailtorepairthecap.Meanwhilethefoamcellsmaydisplaytissuefactor,apotentclotpromoter.Iftheweakenedplaqueruptures,tissuefactorwillinteractwithclot-promotingelementsintheblood,causingathrombus,orclot,toform.Iftheclotisbigenough,itwillhalttheflowofbloodtotheheart,producingaheartattackthedeathofcardiactissue.FibrouscapMigratingsmoothmusclecell,.,5,.,6,.,7,.,8,.,9,.,10,正常动脉结构,.,11,冠脉病变进展,.,12,冠脉狭窄和阻塞,.,13,损伤反应学说,.,14,运动试验心电图,.,15,运动试验,.,16,动脉硬化分期,.,17,血管内皮细胞,.,18,免疫组化检测oxLDL,.,19,白细胞积聚,.,20,.,21,为何分叉处病变多发,.,22,3岁男孩的冠状动脉脂质条纹,.,23,SmoothMuscleCellMigrationandProliferation,.,24,动脉粥样硬化呈阶梯式发展,.,25,FIGURE308.Mechanismsofplaquedisruption,.,26,TheArterialExtracellularMatrix,AngiogenesisinPlaquesPlaqueMineralization,.,27,COMPLICATIONSOFATHEROSCLEROSIS,ArterialStenosesandTheirClinicalImplications,.,28,PlaqueRuptureandThrombosis,Afibrofattyeccentriccoronaryatheroscleroticplaquewithruptureofitsthin,delicatefibrouscap(arrows),exposureofthenecroticlipidcore(NLC)tothebloodstream,andsubsequentluminalthrombosisprecipitatinganacuteischemicepisode,.,29,aorticcomplicatedatheromatouslesion,Grossphotographsillustrateanaorticcomplicatedatheromatouslesionwithruptureofitsfibrouscap(FC).,lipidcore(LC)M=media;T=thrombus,.,30,Rupturedaorticatheroscleroticplaques,Additionalexamplesofrupturedaorticatheroscleroticplaqueswithexposureoftheirlipidcores(LC)tobloodelementsandsubsequentthrombosis.A,Therupturedendsofthefibrouscap(FC),.,31,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.,.,32,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,.,33,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,.,34,ThrombosisDuetoSuperficialErosionoflaques,Superficialerosionofexperimentalatheroscleroticlesionsshownbyscanningelectronmicroscopy.A,Inthelow-powerview,therentinendotheliumisevident.Leukocyteshaveadheredtothesubendothelium,whichisbeginningtobecoveredwithacarpetofplatelets.B,Thehigh-powerviewshowsafieldselectedfromthecenterofAthatshowstheleukocytesandplateletsadherenttothesubendothelium.,.,35,Plateletthrombuscomplicatingaplaquedisruptioninexperimentalatherosclerosis,Thistransmissionelectronmicrographshowsacrosssectionofmacrophagestuddedwithplateletsthathaveclumpedtoformamicroscopicthrombus.,.,36,SPECIALCASESOFARTERIOSCLEROSIS,RestenosisafterArterialIntervention,.,37,Comparisonofusualatherosclerosisandtransplantationarteriosclerosis,.,38,Amultifactorialviewofthepathogenesisofatherosclerosis,.,39,RiskFactorsforAtheroscleroticDisease,.,40,DYSLIPIDEMIA,.,41,Structureoflipoproteins,.,42,Structureoflipoproteins,Theoil-dropormixedmicellemodeloflipoproteinstructureforchylomicron,verylow-densitylipoprotein(VLDL),low-densitylipoprotein(LDL),andhigh-densitylipoprotein(HDL).,.,43,Relativesizeofplasmalipoproteinsaccordingtotheirhydrateddensity.,.,44,TABLE312.APOLIPOPROTEINS,.,45,Cellularcholesterolhomeostasisinvarioustissues,.,46,Schematicdiagramofthelipidtransportsystem,Apo=apolipoprotein;LPL=lipoproteinlipase;HL=hepaticlipase;CETP=cholesterylestertransferprotein;LCAT=lecithincholesterolacyltransferase;FFA=freefattyacids;,.,47,Lipoprotein(a)Lp(a),Lipoprotein(a)Lp(a)representsadistinctgeneticformofLDLwhereinapolipoprotein(a)apo(a)islinkedtoapoB100viacysteineK436ofapo(a)andanunknowncysteinefromthecarboxylendofapoBbydisulfidelinkage,.,48,ManagementofLipoproteinDisorders,.,49,ManagementofLipoproteinDisorders,GENERALAPPROACHES.SPECIFICTREATMENTS,RESINS.HMGCoAREDUCTASEINHIBITORS(STATINS).FIBRICACIDDERIVATIVES(FIBRATES).NICOTINICACID(NIACIN).FISHOILS.MONITORING.OTHERMEDICATIONS.DIETARYSUPPLEMENTS(“NUTRACEUTICALS”).AGGRESSIVEMEASURESFORTREATINGREFRACTORYELEVATIONOFLDL.GENETHERAPY:AFUTUREAPPROACHTODYSLIPIDEMIA?,.,50,饮食控制,Correlationbetweenincreasingdietaryfatandserumcholesterolinpopulationsmigratingtocountrieswithdifferentdietaryhabits.,.,51,Proposedmechanismbywhichdietarysaturatedfattyacidsraiseserumcholesterol,AmechanismbywhichdietarysaturatedfattyacidselevatetheLDLcholesterollevelappearstobedown-regulationoftheexpressionofhepaticLDLreceptors.DietarysaturatedfattyacidshavebeenshowntoinhibitLDLreceptoractivity,althoughtheirmechanismofactionisunclear.,.,52,Thepopulation-basedapproachtocholesterolloweringbydiet,.,53,Mechanismofactionofstatins,Thestatinsinhibittherate-limitingenzyme,hydroxymethylglutaryl-coenzymeA(HMG-CoA)reductase,incholesterolbiosynthesis(1).Themajororgansforcholesterolbiosynthesisarethesmallintestineandliver.TheassociateddecreaseinhepaticandcellularcholesterolconcentrationstimulatestheproductionofLDLreceptors,whichincreasetherateofremovalofLDLfromtheplasma(2).ThereisalsoincreasedremovalofVLDLremnantsandintermediate-densitylipoprotein(IDL),whichareprecursorstoLDLformation.Insomepatients,theremayalsobeadecreaseinlipoproteinsynthesis(3).TheenhancedremovalofVLDLremnantsandIDLandtheinhibitionoflipoproteinsynthesismaycontributetothemodesttr