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RoleofLipoproteinsinInflammation

PhilipBarterandKerry-AnneRyeAtherosclerosisisanInflammatoryDiseaseRossR.NEnglJMed1999;340:115-126.EndotheliumVesselLumenIntimaFoamCellMonocyteCytokinesGrowthFactorsMetalloproteinasesCellProliferation

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theircatabolicremnants>30nm20–22nmPotentiallyproinflammatory9–15nmPotentiallyanti-

inflammatoryStructureofLDLMurphyHCetal.Biochemistry2000;39:9763-970.HydrophobicCore

ofTriglycerideandCholesterylEstersapoBSurfaceMonolayerofPhospholipidsandFreeCholesterolRoleofLDLinInflammationSteinbergDetal.NEnglJMed1989;320:915-924.EndotheliumVesselLumenLDLLDLReadilyEntertheArteryWallWhereTheyMaybeModifiedLDLIntimaModifiedLDLModifiedLDLareProinflammatoryHydrolysisofPhosphatidylcholine

toLysophosphatidylcholineOtherChemicalModificationsOxidationofLipids

andApoBAggregationLDLLDLModifiedLDLStimulateExpressionofMCP-1inEndothelialCellsNavabMetal.JClinInvest1991;88:2039-2046.EndotheliumVesselLumenIntimaMonocyteModifiedLDLMCP-1LDLLDLDifferentiationofMonocytesintoMacrophagesSteinbergDetal.NEnglJMed1989;320:915-924.EndotheliumVesselLumenIntimaMonocyteModifiedLDLModifiedLDLPromote

Differentiationof

Monocytesinto

MacrophagesMCP-1MacrophageLDLLDLModifiedLDLInducesMacrophagestoReleaseCytokinesThatStimulateAdhesionMoleculeExpressioninEndothelialCellsNathanCF.JClinInvest1987;79:319-326.EndotheliumVesselLumenMonocyteModifiedLDLMacrophageMCP-1Adhesion

MoleculesCytokinesIntimaLDLLDLEndotheliumVesselLumenMonocyteMacrophageMCP-1Adhesion

MoleculesSteinbergDetal.NEnglJMed1989;320:915-924.MacrophagesExpressReceptorsThatTakeupModifiedLDLFoamCellModifiedLDLTakenupbyMacrophageIntimaLDLLDLEndotheliumVesselLumenMonocyteMacrophageAdhesion

MoleculesMacrophagesandFoamCellsExpressGrowthFactorsandProteinasesFoamCellIntimaModified

LDLCytokinesCellProliferation

MatrixDegradationGrowthFactors

MetalloproteinasesRossR.NEnglJMed1999;340:115-126.MCP-1EndotheliumVesselLumenMonocyteMacrophageMCP-1Adhesion

MoleculesTheRemnantsofVLDLandChylomicronsareAlsoProinflammatoryFoamCellIntimaModified

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MatrixDegradationDoiHetal.Circulation2000;102:670-676.GrowthFactors

MetalloproteinasesRemnantLipoproteinsRemnantsStructureofHDLRyeKAetal.Atherosclerosis1999;145:227-238.HydrophobicCore

ofTriglycerideandCholesterylEstersapoA-IISurfaceMonolayerofPhospholipidsandFreeCholesterolapoA-ILDLLDLMiyazakiAetal.Biochim

Biophys

Acta1992;1126:73-80.EndotheliumVesselLumenMonocyteModifiedLDLMacrophageMCP-1Adhesion

MoleculesCytokinesHDLPreventFormationofFoamCellsIntimaHDLPromoteCholesterolEffluxFoam

CellLDLLDLMacknessMIetal.BiochemJ1993;294:829-834.EndotheliumVesselLumenMonocyteModifiedLDLMacrophageMCP-1Adhesion

MoleculesCytokinesHDLInhibittheOxidativeModificationofLDLFoam

CellHDLPromoteCholesterolEffluxIntimaHDLInhibit

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ofLDLInhibitionofLDLOxidationbyHDL:

RoleofParaoxonaseParaoxonaseistransportedinplasmaasacomponentofHDLParaoxonaseisknowntoinhibittheoxidativemodificationofLDLThus,thepresenceofparaoxonaseinHDLmayaccountforaproportionoftheantioxidantpropertiesoftheselipoproteinsMacknessMIetal.FEBSLett1991;286:152-154.RoleofHDLApolipoproteinsinRemovingOxidizedLipidsfromLDLCETPtransfersoxidizedlipidsfromLDLtoHDLTheoxidizedlipidsinHDLarereducedbyHDLapolipoproteinsThelivertakesupreducedlipidsfromHDLmorerapidlythanfromLDLChristisonJKetal.JLipidRes1995;36:2017-2026;GardnerBetal.JBiol

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CellHDLPromoteCholesterolEffluxEndotheliumVesselLumenMCP-1E-SelectinCharoIF.Curr

Opin

Lipidol1992;3:335-343.RecruitmentofBloodMonocytesbyEndothelialCellAdhesionMoleculesIntimaVCAM-1ICAM-1StickingMonocyteRollingTransmigrationHDLInhibitEndothelialCellSphingosine

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Chem1999;274:33143-33147.SphingomyelinCeramideSphingosineSph-1-PHDLNF-KBAdhesionProteinSynthesisSM-aseSph

Kinase+TNFXHeterogeneityofHDLRyeKAetal.Atherosclerosis1999;145:227-238.ApolipoproteinCompositionA-IHDLA-I/A-IIHDLA-IIHDLParticleShapeDiscoidalSphericalLipidCompositionTG,CE,andPLParticleSizeHDL2bHDL2aHDL3aHDL3bHDL3cInhibitionofEndothelialCellVCAM-1ExpressionbyHDL:EffectofHDLCompositionInhibitionunaffectedbyreplacingapoA-IwithapoA-IIInhibitionunaffectedbyreplacingapoA-IwithSAAInhibitionunaffectedbyvaryingthecholesterylesterortriglyceridecontentofHDLInhibitionISaffectedbyvaryingHDLphospholipidsBakerPWetal.JLipidRes1999;40:345-353.FattyAcylMoietyinPosition%OccurrenceSubbaiahPVetal.Biochim

Biophys

Acta1989;1003:145-150.PhosphatidylcholineCompositionofHumanHDLPO=1-palmitoyl-2-oleoyl-;PL=1-palmitoyl-2-linoleoyl-;PA=1-palmitoyl-2-arachidonyl-FattyAcylMoietyinPosition16:018:118:220:320:420:522:618:118:220:320:420:518:118:220:420:518:216:018:018:118:2POPC,PLPCandPAPCaccountfor55%ofallPCmolecularspeciesPOPLPAVCAM-1Expression

(%ofcontrol)BakerPWetal.JLipidRes2000;41:1261-1267.InhibitionofEndothelialCellVCAM-1ExpressionbyHDL:EffectofHDLPhospholipidComposition

POPC02468PAPCPLPCrHDLParticleMolarity(mM)PL=1-palmitoyl-2-linoleoyl-;PA=1-palmitoyl-2-arachidonyl-;PO=1-palmitoyl-2-oleoyl-;

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lipopolysaccharidesTheacutephasereactantSAAbindstoplasmaHDL,whichpossiblyneutralizestheeffects

ofSAABaumbergerCetal.Pathobiology1991;59:378-383;BendittEPetal.ProcNatl

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SciUSA1977;74:4025-4028.AnimalStudiesIncreasingtheconcentrationofLDLorremnantparticlesinanimalmodelsresultsinexpressionofendothelialcelladhesionmoleculesatthesiteswhereatheroscleroticlesionsdevelopInfusionoroverexpressionofapoA-IinanimalmodelsreducesoxidationofLDLandreducesendothelialcelladhesionmoleculeexpressionSakaiAetal.Arterioscler

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