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1、第十三章動(dòng)脈粥樣硬化和高血壓AtherosclerosisandHypertension心血管疾?。╟ardiovasculardisease,CVD）發(fā)病率和死亡率居所有疾病之首發(fā)病率↑：90年代-200萬(wàn)/年以上2000年-1700萬(wàn)，總死亡人數(shù)1/32020年-2500萬(wàn)80%在發(fā)展中國(guó)家一種與血脂異常及血管壁成分改變有關(guān)的動(dòng)脈疾病，主要累及彈性動(dòng)脈和較多彈性纖維的肌性動(dòng)脈，病變特征是血中脂質(zhì)在動(dòng)脈內(nèi)膜沉積，引起內(nèi)膜灶性纖維性增厚，病灶深部為由壞死組織和細(xì)胞外脂質(zhì)池形成的粥樣物質(zhì)（粥樣斑塊=纖維帽+脂質(zhì)核）。動(dòng)脈粥樣硬化（atheroscle
2、rosis）Atheroscleroticplaquehas2maincomponents:asoft,lipid-richcoreandahard,collagen-richfibrouscap.Instableplaques,athickfibrouscapmayrepresent>70%ofplaquevolume.Itstabilizestheplaqueandpreventsitfromundergoingrupture.Incontrast,unstableplaquehasathinfibrouscapandisatgreaterri
3、skforrupture.Inunstableplaque,thelipid-richcoremayrepresentthemajorityoftheplaquevolume.Thecoreisrichinextracellularlipids,whichareformedbytrappingblood-derivedlipids,notablylow-densitylipoprotein,orbylipid-filledmacrophages,knownasfoamcells.Theplaquedestabilizesduetoinflammat
4、ionbyfoamcellsandotherinflammatorymediatorsthatmaketheplaquemorevulnerabletorupture.Thiscommonlyoccursatthejunctionoftheplaqueandthelessdiseasedvesselwall.Asaresult,thelipidcoremaybeexposedtoflowingbloodleadingtoplatelet-mediatedthrombusformation.Falkreviewedtheworkofotherinve
5、stigatorsregardingtheseverityofstenosisanditsassociationwiththeriskofMI.Resultsshowedthat>86%ofMIsresultedfromlesionsthatwere<70%stenosed.MostexpertspriortoFalkthoughtthatpatientshadheartattacksbecauseofblockagesthatincreasedinsizeuntiltheyblockedthebloodvesselandcausedahearta
6、ttack.1BasedonthefindingsofFalk,wenowknowtheprimarycauseofaheartattackistheruptureofunstableplaquesthatare<70%stenosedandareclinicallysilent.Approximately200patientsfrom4studieswerestudiedtogeneratetheseresults,whichhavebeenconfirmedinotherstudies.1不穩(wěn)定斑塊（unstableplaque）指脂質(zhì)核較大、
7、病變偏心、纖維帽較薄、炎癥細(xì)胞浸潤(rùn)較重、在受到外力作用時(shí)容易破裂的斑塊，又稱脆性斑塊（vulnerableplaque）。穩(wěn)定斑塊（stableplaque）oxLDL可能參與動(dòng)脈粥樣硬化發(fā)生發(fā)展的全過(guò)程：1.對(duì)內(nèi)皮細(xì)胞的作用使內(nèi)皮細(xì)胞損傷，誘導(dǎo)內(nèi)皮細(xì)胞表達(dá)多種黏附分子，增強(qiáng)單核細(xì)胞和T淋巴細(xì)胞黏附及向內(nèi)皮下移行2.對(duì)單核巨噬細(xì)胞的作用促使單核細(xì)胞向巨噬細(xì)胞轉(zhuǎn)化，吞噬脂質(zhì)形成泡沫細(xì)胞。3.對(duì)平滑肌細(xì)胞的作用使平滑肌細(xì)胞由收縮型向合成型轉(zhuǎn)變，并促使平滑肌細(xì)胞游走；誘發(fā)細(xì)胞增殖的基因表達(dá)，促進(jìn)平滑肌細(xì)胞增生4.對(duì)血小板的作用可引起血小板黏附、聚集，促進(jìn)
8、血栓形成sLDL：LDL亞型中的小顆粒低密度脂蛋白：具有經(jīng)LDL受體清除緩慢、已粘附于血管壁及抗氧化能力低等特點(diǎn)3.脂蛋白
