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簡介：REVIEWENDOTHELIALSHEARSTRESSINTHEEVOLUTIONOFCORONARYATHEROSCLEROTICPLAQUEANDVASCULARREMODELLINGCURRENTUNDERSTANDINGANDREMAININGQUESTIONSJOLANDAJWENTZEL1,YIANNISSCHATZIZISIS2,3,FRANKJHGIJSEN1,GEORGEDGIANNOGLOU3,CHARLESLFELDMAN2,ANDPETERHSTONE21BIOMEDICALENGINEERING,DEPARTMENTCARDIOLOGY,ERASMUSMC,ROTTERDAM,THENETHERLANDS2CARDIOVASCULARDIVISION,BRIGHAMANDWOMEN’SHOSPITAL,HARVARDMEDICALSCHOOL,BOSTON,MA,USAAND31STDEPARTMENTOFCARDIOLOGY,AHEPAUNIVERSITYHOSPITAL,ARISTOTLEUNIVERSITYMEDICALSCHOOL,THESSALONIKI,GREECERECEIVED23MARCH2012REVISED12JUNE2012ACCEPTED25JUNE2012ONLINEPUBLISHAHEADOFPRINT29JUNE2012ABSTRACTTHEHETEROGENEITYOFPLAQUEFORMATION,THEVASCULARREMODELLINGRESPONSETOPLAQUEFORMATION,ANDTHECONSEQUENTPHENOTYPEOFPLAQUEINSTABILITYATTESTTOTHEEXTRAORDINARILYCOMPLEXPATHOBIOLOGYOFPLAQUEDEVELOPMENTANDPROGRESSION,CULMINATINGINDIFFERENTCLINICALCORONARYSYNDROMESATHEROSCLEROTICPLAQUESPREDOMINANTLYFORMINREGIONSOFLOWENDOTHELIALSHEARSTRESSESS,WHEREASREGIONSOFMODERATE/PHYSIOLOGICALANDHIGHESSAREGENERALLYPROTECTEDLOWESSINDUCEDCOMPENSATORYEXPANSIVEREMODELLINGPLAYSANIMPORTANTROLEINPRESERVINGLUMENDIMENSIONSDURINGPLAQUEPROGRESSION,BUTWHENTHEEXPANSIVEREMODELLINGBECOMESEXCESSIVEPROMOTESCONTINUEDINFLUXOFLIPIDSINTOTHEVESSELWALL,VULNERABLEPLAQUEFORMATIONANDPOTENTIALPRECIPITATIONOFANACUTECORONARYSYNDROMEADVANCEDPLAQUESWHICHSTARTTOENCROACHINTOTHELUMENEXPERIENCEHIGHESSATTHEIRMOSTSTENOTICREGION,WHICHAPPEARSTOPROMOTEPLAQUEDESTABILIZATIONTHISREVIEWDESCRIBESTHEROLEOFESSFROMEARLYATHEROGENESISTOEARLYPLAQUEFORMATION,PLAQUEPROGRESSIONTOADVANCEDHIGHRISKSTENOTICORNONSTENOTICPLAQUE,ANDPLAQUEDESTABILIZATIONTHECRITICALIMPLICATIONOFTHEVASCULARREMODELLINGRESPONSETOPLAQUEGROWTHISALSODISCUSSEDCURRENTDEVELOPMENTSINTECHNOLOGYTOCHARACTERIZELOCALESSANDVASCULARREMODELLINGINVIVOMAYPROVIDEARATIONALEFORINNOVATIVEDIAGNOSTICANDTHERAPEUTICSTRATEGIESFORCORONARYPATIENTSTHATAIMTOPREVENTCLINICALCORONARYSYNDROMESKEYWORDSSHEARSTRESS?HIGHRISKPLAQUE?INFLAMMATION?VASCULARREMODELLING1INTRODUCTIONATHEROSCLEROTICPLAQUESAREREGIONSINTHEARTERIALSYSTEMCHARACTERIZEDBYINTIMALTHICKENINGWITHEXCESSIVEBUILDUPOFOXIDIZEDLOWDENSITYLIPOPROTEINCHOLESTEROLACCOMPANIEDBYINFLAMMATORYCELLINFILTRATION,SMOOTHMUSCLEPROLIFERATION,ANDEXTRACELLULARMATRIXACCUMULATION1PLAQUESPRONETORUPTURESOCALLEDVULNERABLEPLAQUESAREFURTHERCHARACTERIZEDBYTHEPRESENCEOFALARGENECROTICCORECOVEREDBYANINFLAMEDTHINFIBROUSCAP2RUPTUREOFAVULNERABLECORONARYATHEROSCLEROTICPLAQUEISRESPONSIBLEFORTHEMAJORITYOFACUTECORONARYEVENTS,3WHICHARETHELEADINGCAUSEOFMORBIDITYANDMORTALITYINTHEWESTERNWORLDALTHOUGHTHERISKFACTORSFORATHEROSCLEROTICPLAQUEFORMATION,INCLUDINGHIGHCHOLESTEROL,DIABETES,ANDHIGHBLOODPRESSURE,ARESYSTEMICINNATURE,PLAQUESARELOCATEDATSPECIFICSITESINTHEARTERIALSYSTEMTHESESITESINCLUDESIDEBRANCHES,THEOUTERWAISTOFBIFURCATIONS,ORTHEINNERCURVEOFARTERIES,WHEREDISTURBEDFLOWANDLOWENDOTHELIALSHEARSTRESSESSOCCUR4–7INCONTRAST,ARTERIALREGIONSEXPOSEDTOMODERATE/PHYSIOLOGICALESSAREPROTECTEDFROMATHEROSCLEROSISEARLYOBSERVATIONSONTHERELATIONSHIPBETWEENESSANDPLAQUELOCALIZATIONWEREBASEDMAINLYONAUTOPSYMATERIAL,8,9ANDCONSEQUENTLYDIDNOTALLOWINVESTIGATIONOFTHEINFLUENCEOFESSONATHEROSCLEROSISTHEADVENTOFTHREEDIMENSIONAL3DRECONSTRUCTIONTECHNIQUESFORCORONARYARTERIESINVIVO,10–13BASEDONBIPLANEANGIOGRAPHYANDCORRESPONDINGAUTHORSJJWISATBIOMECHANICSLABORATORY,BIOMEDICALENGINEERING,EE2322,ERASMUSMC,POBOX2040,3000CAROTTERDAM,THENETHERLANDSYSCISATFIRSTDEPARTMENTOFCARDIOLOGY,AHEPAUNIVERSITYHOSPITAL,ARISTOTLEUNIVERSITYMEDICALSCHOOL,1STYLPKURIAKIDISTREET,54636,THESSALONIKI,GREECETEL31107044044JJW,302310994837YSCFAX31107044720,EMAILJWENTZELERASMUSMCNLJJWJOCMEDAUTHGRYSCPUBLISHEDONBEHALFOFTHEEUROPEANSOCIETYOFCARDIOLOGYALLRIGHTSRESERVEDFIGURE3BOFNOTE,THEABSOLUTECUTOFFPOINTFORLOWESSAPPEARSTOBEDEPENDENTONCONCOMITANTCONDITIONSASPRESENTEDBELOWSECTION3LOWESSTYPICALLYOCCURSATTHEINNERAREASOFCURVATURESANDPOTENTIALLYATTHEUPSTREAMSHOULDERSOFASTENOSISLOWOSCILLATORYESSISBIDIRECTIONAL,WITHAFLUCTUATINGMAGNITUDEBETWEENSYSTOLEANDDIASTOLE,RESULTINGINALOWTIMEAVERAGEAPPROXIMATELY,10–15PAFIGURE3BLOWOSCILLATORYESSOCCURSPRIMARILYDOWNSTREAMOFSTENOSES,ATTHELATERALWALLSOFBIFURCATIONSANDATTHEOSTIAOFBRANCHESHIGHESSISCHARACTERIZEDBYASIGNIFICANTLYHIGHTIMEAVERAGEAPPROXIMATELY30PAANDOCCURSATTHEUPSTREAMANDMOSTSTENOTICSITEOFTHEPLAQUE3DYNAMICNATUREOFLOCALESSESSISADYNAMICFACTORTHATCHANGESINDIRECTIONANDMAGNITUDEWITHPLAQUEFORMATIONANDVASCULARREMODELLING35ASACONTINUOUSVARIABLE,ESSCOVERSAWIDESPECTRUMOFVALUES,FROMLOWESSTOMODERATE/PHYSIOLOGICALESSANDTOHIGHESSTHECUTOFFPOINTSDEFININGLOW,MODERATE/PHYSIOLOGICAL,ANDHIGHESSMAYVARYAMONGSPECIES,ANDAMONGVASCULARBEDSEGFEMORAL,CAROTID,ANDCORONARYARTERIESINTHESAMESPECIES36EVENINTHESAMEVASCULARLOCATION,ESSCHANGESOVERTIMEINRESPONSETOSEVERALSYSTEMICANDLOCALFACTORSTHESEVERITYOFSYSTEMICRISKFACTORSEGHYPERCHOLESTEROLAEMIACERTAINLYINFLUENCESTHEEFFECTOFTHELOCALHAEMODYNAMICENVIRONMENTFURTHERMORE,THESTAGEOFATHEROSCLEROSISDEVELOPMENT,THEREMODELLINGRESPONSEOFTHEWALLTOPLAQUEFORMATION,ASWELLASREGIONALSTRUCTURALANDSTIFFNESSCHARACTERISTICSCRITICALLYDETERMINETHELOCALESSENVIRONMENTANDTHESUBSEQUEN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