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RoleofLipoproteinsinInflammation
PhilipBarterandKerry-AnneRyeAtherosclerosisisanInflammatoryDiseaseRossR.NEnglJMed1999;340:115-126.EndotheliumVesselLumenIntimaFoamCellMonocyteCytokinesGrowthFactorsMetalloproteinasesCellProliferation
MatrixDegradationMacrophageLipoproteinClassesandInflammationDoiHetal.Circulation2000;102:670-676;ColomeCetal.Atherosclerosis2000;
149:295-302;CockerillGWetal.Arterioscler
Thromb
Vasc
Biol1995;15:1987-1994.HDLLDLChylomicrons,
VLDL,and
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
RemnantsCytokinesCellProliferation
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
Oxidation
ofLDLInhibitionofLDLOxidationbyHDL:
RoleofParaoxonaseParaoxonaseistransportedinplasmaasacomponentofHDLParaoxonaseisknowntoinhibittheoxidativemodificationofLDLThus,thepresenceofparaoxonaseinHDLmayaccountforaproportionoftheantioxidantpropertiesoftheselipoproteinsMacknessMIetal.FEBSLett1991;286:152-154.RoleofHDLApolipoproteinsinRemovingOxidizedLipidsfromLDLCETPtransfersoxidizedlipidsfromLDLtoHDLTheoxidizedlipidsinHDLarereducedbyHDLapolipoproteinsThelivertakesupreducedlipidsfromHDLmorerapidlythanfromLDLChristisonJKetal.JLipidRes1995;36:2017-2026;GardnerBetal.JBiol
Chem1998;273:6088-6095.LDLLDLCockerillGWetal.Arterioscler
Thromb
Vasc
Biol1995;15:1987-1994.EndotheliumVesselLumenMonocyteModifiedLDLMacrophageMCP-1Adhesion
MoleculesCytokinesInhibitionofAdhesionMoleculesIntimaHDLInhibit
Oxidation
ofLDLHDLInhibitAdhesionMoleculeExpressionFoam
CellHDLPromoteCholesterolEffluxEndotheliumVesselLumenMCP-1E-SelectinCharoIF.Curr
Opin
Lipidol1992;3:335-343.RecruitmentofBloodMonocytesbyEndothelialCellAdhesionMoleculesIntimaVCAM-1ICAM-1StickingMonocyteRollingTransmigrationHDLInhibitEndothelialCellSphingosine
KinaseXiaPetal.JBiol
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-;
rHDL=reconstitutedHDLAdditionalAnti-inflammatoryPropertiesofHDLHDLbindandneutralizeproinflammatory
lipopolysaccharidesTheacutephasereactantSAAbindstoplasmaHDL,whichpossiblyneutralizestheeffects
ofSAABaumbergerCetal.Pathobiology1991;59:378-383;BendittEPetal.ProcNatl
Acad
SciUSA1977;74:4025-4028.AnimalStudiesIncreasingtheconcentrationofLDLorremnantparticlesinanimalmodelsresultsinexpressionofendothelialcelladhesionmoleculesatthesiteswhereatheroscleroticlesionsdevelopInfusionoroverexpressionofapoA-IinanimalmodelsreducesoxidationofLDLandreducesendothelialcelladhesionmoleculeexpressionSakaiAetal.Arterioscler
Thromb
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Biol1997;17:310-316;DimayugaPetal.Biochem
Biophys
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Commun1999;264:465-468;CockerillGWetal.Circulation2001;103:108-112;TheilmeierGetal.FASEBJ2000;14:2032-2039.StudiesinHumansTreatmentsthatreducethelevelofLDLreducetheplasmalevelsofC-reactiveproteinandsolubleadhesionmolecules
BUTTheseef
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