高级病生第6次课动脉硬化讲座硕士班.ppt
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1、动脉粥样硬化发生机理的研究进展,赵 明 教授,南方医科大学 基础医学院 病理生理学教研室,二零零九年十二月七日,“Chronic inflammatory disorder of intima of large blood vessels characterised by formation of fibrofatty plaques called atheroma”. Hardening of arteries - Arteriosclerosis,Arteriosclerosis,Lumen,Fibrous cap,Endothelial cells,Atherosclerosis,Lip
2、id metabolism imbalance Inflammation Immuno-response,Lipid metabolism imbalance,Classification of lipids and lipoproteins,Characteristics of lipoproteins,Digestion and metabolism of dietary fat,HDL metabolism and reverse cholesterol transport,Cholesterol efflux and reverse cholesterol transport is m
3、odulated by two receptors,PPAR activators induce cholesterol efflux and reverse cholesterol transport,HDL metabolism: 5 key genes,PPAR: apo A-l, apo A-ll, LPL, ABCA-1 and SR-BI expression,PPARa activators induce cholesterol efflux from human macrophages,CLA-1/SR-BI protein may promote cholesterol re
4、moval from peripheral cells,CLA-1 expression is regulated by PPAR activators in differentiated human macrophages,PPAR activators induce cholesterol efflux and reverse cholesterol transport,LDL,The early lesion: modified lipoproteins and foam cell formation,Classes of Scavenger Receptors,Pluddemann e
5、t al. Methods 43 (2007) 207-217,The Scavenger Receptor Families for modified LDL,The macrophage as an inflammatory mediator,Statins induce PPAR activity,Lumen,Fibrous cap,Endothelial cells,Inflammation,Immuno-response,TLRs and atherosclerosis,CD14,TLR4,MD2,MyD88,TRAM,TRIF,Mal/Tirap,TLR1,TLR2,TLR6,TL
6、R2,TLR4,MyD88,MyD88,Bjrkbacka et al. Nat. Med. (2004) 10: 416-421,Why does oxidized LDL become immunogenic?,Fragmentation of apo B-100 Oxidation of phospholipids Formation of covalent aldehyde (MDA) and amino acid adducts,How Does Immunization With Oxidized LDL Affect Atherosclerosis?,Reduced develo
7、pment of atherosclerosis in rabbits (Palinski et al PNAS 1995, Ameli et al ATVB 1996) Reduced development of atherosclerosis in apo E deficient mice (George et al Atherosclerosis 1998, Freigang et al ATVB 1998, Zhou et al ATVB 2001),Is it possible to produce a vaccine against atherosclerosis?,What s
8、tructures in oxidized LDL are recognized by the immune system? Are these immune responses associated with cardiovascular disease in humans? Can protective immune responses be selectively activated by a vaccine? Can antibodies be used directly to treat atherosclerosis?,Characterization of epitopes in
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