资源描述
Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Role of Lipoproteins in Inflammation,Philip Barter and Kerry-Anne Rye,Role of Lipoproteins in Inflam,Atherosclerosis is an Inflammatory Disease,Ross R.,N Engl J Med,1999;340:115-126.,Endothelium,Vessel Lumen,Intima,Foam Cell,Monocyte,Cytokines,Growth Factors,Metalloproteinases,Cell ProliferationMatrix Degradation,Macrophage,Atherosclerosis is an Inflamma,Lipoprotein Classes and Inflammation,Doi H et al.,Circulation,2000;102:670-676;Colome C et al.,Atherosclerosis,2000;149:295-302;Cockerill GW et al.,Arterioscler Thromb Vasc Biol,1995;15:1987-1994.,HDL,LDL,Chylomicrons,VLDL,and their catabolic remnants,30 nm,2022 nm,Potentially proinflammatory,915 nm,Potentially anti-inflammatory,Lipoprotein Classes and Inflam,Structure of LDL,Murphy HC et al.,Biochemistry,2000;39:9763-970.,Hydrophobic Core of Triglyceride and Cholesteryl Esters,apoB,Surface Monolayer of Phospholipids and Free Cholesterol,Structure of LDLMurphy HC et a,Role of LDL in Inflammation,Steinberg D et al.,N Engl J Med,1989;320:915-924.,Endothelium,Vessel Lumen,LDL,LDL Readily Enter the Artery Wall Where They May be Modified,LDL,Intima,Modified LDL,Modified LDL are Proinflammatory,Hydrolysis of Phosphatidylcholineto Lysophosphatidylcholine,Other Chemical Modifications,Oxidation of Lipidsand ApoB,Aggregation,Role of LDL in InflammationSte,LDL,LDL,Modified LDL Stimulate Expression of MCP-1 in Endothelial Cells,Navab M et al.,J Clin Invest,1991;88:2039-2046.,Endothelium,Vessel Lumen,Intima,Monocyte,Modified LDL,MCP-1,LDLLDLModified LDL Stimulate E,LDL,LDL,Differentiation of Monocytes into Macrophages,Steinberg D et al.,N Engl J Med,1989;320:915-924.,Endothelium,Vessel Lumen,Intima,Monocyte,Modified LDL,Modified LDL PromoteDifferentiation ofMonocytes intoMacrophages,MCP-1,Macrophage,LDLLDLDifferentiation of Monoc,LDL,LDL,Modified LDL Induces Macrophages to Release Cytokines That Stimulate Adhesion Molecule Expression in Endothelial Cells,Nathan CF.,J Clin Invest,1987;79:319-326.,Endothelium,Vessel Lumen,Monocyte,Modified LDL,Macrophage,MCP-1,AdhesionMolecules,Cytokines,Intima,LDLLDLModified LDL Induces Mac,LDL,LDL,Endothelium,Vessel Lumen,Monocyte,Macrophage,MCP-1,AdhesionMolecules,Steinberg D et al.,N Engl J Med,1989;320:915-924.,Macrophages Express Receptors That Take up Modified LDL,Foam Cell,Modified LDL Taken up by Macrophage,Intima,LDLLDLEndotheliumVessel LumenM,LDL,LDL,Endothelium,Vessel Lumen,Monocyte,Macrophage,AdhesionMolecules,Macrophages and Foam Cells Express Growth Factors and Proteinases,Foam Cell,Intima,Modified LDL,Cytokines,Cell ProliferationMatrix Degradation,Growth FactorsMetalloproteinases,Ross R.,N Engl J Med,1999;340:115-126.,MCP-1,LDLLDLEndotheliumVessel LumenM,Endothelium,Vessel Lumen,Monocyte,Macrophage,MCP-1,AdhesionMolecules,The Remnants of VLDL and Chylomicrons are Also Proinflammatory,Foam Cell,Intima,ModifiedRemnants,Cytokines,Cell ProliferationMatrix Degradation,Doi H et al.,Circulation,2000;102:670-676.,Growth FactorsMetalloproteinases,Remnant Lipoproteins,Remnants,EndotheliumVessel LumenMonocyt,Structure of HDL,Rye KA et al.,Atherosclerosis,1999;145:227-238.,Hydrophobic Core of Triglyceride and Cholesteryl Esters,apoA-II,Surface Monolayer of Phospholipids and Free Cholesterol,apoA-I,Structure of HDLRye KA et al.,LDL,LDL,Miyazaki A et al.,Biochim Biophys Acta,1992;1126:73-80.,Endothelium,Vessel Lumen,Monocyte,Modified LDL,Macrophage,MCP-1,AdhesionMolecules,Cytokines,HDL Prevent Formation of Foam Cells,Intima,HDL Promote Cholesterol Efflux,Foam Cell,LDLLDLMiyazaki A et al.Biochi,LDL,LDL,Mackness MI et al.,Biochem J,1993;294:829-834.,Endothelium,Vessel Lumen,Monocyte,Modified LDL,Macrophage,MCP-1,AdhesionMolecules,Cytokines,HDL Inhibit the Oxidative Modification of LDL,Foam Cell,HDL Promote Cholesterol Efflux,Intima,HDL InhibitOxidationof LDL,LDLLDLMackness MI et al.Bioch,Inhibition of LDL Oxidation by HDL:,Role of Paraoxonase,Paraoxonase is transported in plasma as a component of HDL,Paraoxonase is known to inhibit the oxidative modification of LDL,Thus,the presence of paraoxonase in HDL may account for a proportion of the antioxidant properties of these lipoproteins,Mackness MI et al.,FEBS Lett,1991;286:152-154.,Inhibition of LDL Oxidation by,Role of HDL Apolipoproteins in Removing Oxidized Lipids from LDL,CETP transfers oxidized lipids from LDL to HDL,The oxidized lipids in HDL are reduced by HDL apolipoproteins,The liver takes up reduced lipids from HDL more rapidly than from LDL,Christison JK et al.,J Lipid Res,1995;36:2017-2026;Gardner B et al.,J Biol Chem,1998;273:6088-6095.,Role of HDL Apolipoproteins in,LDL,LDL,Cockerill GW et al.,Arterioscler Thromb Vasc Biol,1995;15:1987-1994.,Endothelium,Vessel Lumen,Monocyte,Modified LDL,Macrophage,MCP-1,AdhesionMolecules,Cytokines,Inhibition of Adhesion Molecules,Intima,HDL InhibitOxidationof LDL,HDL Inhibit Adhesion Molecule Expression,Foam Cell,HDL Promote Cho
展开阅读全文