Fig. 10.10 ). Several growth factors are implicated in SMC proliferation and matrix synthesis, including platelet-derived growth factor (released by locally adherent platelets, macrophages, ECs, and SMCs), fibroblast growth factor, and TGF-α. The recruited SMCs synthesize ECM (most notably collagen), which stabilizes atherosclerotic plaques. However, activated inflammatory cells in atheromas also can cause intimal SMC apoptosis and breakdown of matrix, leading to the development of unstable plaques (see later).
MORPHOLOGYThedevelopmentofatherosclerosistendstofollowaseriesofmorphologicchangesdescribedbelow.
Fatty Streaks. Fattystreaksbeginasminuteyellow,flatmaculesthatcoalesceintoelongatedlesions,1cmormoreinlength(
Fig.10.11 ).Theyarecomposedoflipid-filledfoamymacrophagesbutareonlyminimallyraisedanddonotcauseanysignificantflowdisturbance.Fattystreakscanappearintheaortasofinfantsyoungerthan1yearofageandarepresentinvirtuallyallchildrenolderthan10yearsofage,regardlessofgenetic,clinical,ordietaryriskfactors.Notallfattystreaksaredestinedtoprogresstoatheroscleroticplaques.Nevertheless,itisnotablethatcoronaryfattystreaksformduringadolescenceatthesameanatomicsitesthatarepronetoplaqueslaterinlife.
Atherosclerotic Plaque. Thekeyfeaturesoftheselesionsareintimalthickeningandlipidaccumulation(see
Fig.10.7 ).Atheromatousplaquesarewhitetoyellowraisedlesions;theyrangefrom0.3to1.5cmindiameterbutcancoalescetoformlargermasses.Thrombussuperimposedonulceratedplaquesimpartsared-browncolor(
Fig.10.12
Atheroscleroticplaquesarepatchy,usuallyinvolvingonlyaportionofanygivenarterialwall;oncross-section,therefore,thelesionsappear“eccentric”(
Fig.10.13A ).Thefocalnatureofatheroscleroticlesionsmayberelatedtothevagariesofvascularhemodynamics.Localflowdisturbances,suchasturbulenceatbranchpoints,makecertainpartsofavesselwallespeciallysusceptibletoplaqueformation.
Indescendingorderofseverity,atherosclerosisinvolvestheinfrarenalabdominalaorta,thecoronaryarteries,thepoplitealarteries,theinternalcarotidarteries,andthevesselsofthecircleofWillis.Eveninthesamepatient,atherosclerosistypicallyismoresevereintheabdominalaortathaninthethoracicaorta.Vesselsoftheupperextremitiesusuallyarespared,asarethemesentericandrenalarteries,exceptattheirostia.Itisimportanttonotethattheseverityofatherosclerosisinonevascularlocationdoesnotnecessarilypredictitsseverityinanother(e.g.,aortaversuscoronaryarteries);nevertheless,anygivenpatienttendstoshowcomparableseverityofdiseasethroughouthisorhervasculature.Finally,inanygivenvessel,lesionsatvariousstagesofseverityoftencoexist.
Atherosclerotic plaques have three principal components:(1) cells,including SMCs,macrophages,and T cells; http://ebooksmedicine.net
Fig. 10.11 Fattystreaks.(A)Aortawithfattystreaks(arrows), mainlyneartheostiaofbranchvessels.(B)Fattystreakinanexperimentalhypercholesterolemicrabbit,demonstratingintimal,macrophage-derivedfoamcells(arrows).(B,Courtesy of Myron I.Cybulsky,MD,University of Toronto,Toronto,Ontario,Canada.)