脂蛋白在动脉粥样硬化炎症中的作用优选课件.ppt

1、Ross R.N Engl J Med 1999;340:115-126.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.Murphy HC et al.Biochemistry 2000;39:9763-970.Steinberg D et al.N Engl J Med 1989;320:915-924.Navab M et al

2、.J Clin Invest 1991;88:2039-2046.Steinberg D et al.N Engl J Med 1989;320:915-924.Nathan CF.J Clin Invest 1987;79:319-326.Steinberg D et al.N Engl J Med 1989;320:915-924.Ross R.N Engl J Med 1999;340:115-126.Doi H et al.Circulation 2000;102:670-676.Rye KA et al.Atherosclerosis 1999;145:227-238.Miyazak

3、i A et al.Biochim Biophys Acta 1992;1126:73-80.Mackness MI et al.Biochem J 1993;294:829-834.nParaoxonase is transported in plasma as a component of HDLnParaoxonase is known to inhibit the oxidative modification of LDLnThus,the presence of paraoxonase in HDL may account for a proportion of the antiox

4、idant properties of these lipoproteinsMackness MI et al.FEBS Lett 1991;286:152-154.nCETP transfers oxidized lipids from LDL to HDLnThe oxidized lipids in HDL are reduced by HDL apolipoproteinsnThe liver takes up reduced lipids from HDL more rapidly than from LDLChristison JK et al.J Lipid Res 1995;3

5、6:2017-2026;Gardner B et al.J Biol Chem 1998;273:6088-6095.Cockerill GW et al.Arterioscler Thromb Vasc Biol 1995;15:1987-1994.Charo IF.Curr Opin Lipidol 1992;3:335-343.Xia P et al.J Biol Chem 1999;274:33143-33147.Rye KA et al.Atherosclerosis 1999;145:227-238.nInhibition unaffected by replacing apoA-

6、I with apoA-IInInhibition unaffected by replacing apoA-I with SAAnInhibition unaffected by varying the cholesteryl ester or triglyceride content of HDLnInhibition affected by varying HDL phospholipidsBaker PW et al.J Lipid Res 1999;40:345-353.05101520253035Fatty Acyl Moiety in Position%OccurrenceSub

7、baiah PV et al.Biochim Biophys Acta 1989;1003:145-150.PO=1-palmitoyl-2-oleoyl-;PL=1-palmitoyl-2-linoleoyl-;PA=1-palmitoyl-2-arachidonyl-Fatty Acyl Moiety in Position16:018:118:220:320:420:522:618:118:220:320:420:518:118:220:420:518:216:018:018:118:2POPC,PLPC and PAPC account for 55%of all PC molecul

8、ar speciesPOPLPA020406080100120VCAM-1 Expression(%of control)Baker PW et al.J Lipid Res 2000;41:1261-1267.POPC02468PAPCPLPCrHDL Particle Molarity(mM)PL=1-palmitoyl-2-linoleoyl-;PA=1-palmitoyl-2-arachidonyl-;PO=1-palmitoyl-2-oleoyl-;rHDL=reconstituted HDLnHDL bind and neutralize proinflammatory lipop

9、olysaccharidesnThe acute phase reactant SAA binds to plasma HDL,which possibly neutralizes the effects of SAABaumberger C et al.Pathobiology 1991;59:378-383;Benditt EP et al.Proc Natl Acad Sci U S A 1977;74:4025-4028.nIncreasing the concentration of LDL or remnant particles in animal models results

10、in expression of endothelial cell adhesion molecules at the sites where atherosclerotic lesions developnInfusion or overexpression of apoA-I in animal models reduces oxidation of LDL and reduces endothelial cell adhesion molecule expressionSakai A et al.Arterioscler Thromb Vasc Biol 1997;17:310-316;

11、Dimayuga P et al.Biochem Biophys Res Commun 1999;264:465-468;Cockerill GW et al.Circulation 2001;103:108-112;Theilmeier G et al.FASEB J 2000;14:2032-2039.nTreatments that reduce the level of LDL reduce the plasma levels of C-reactive protein and soluble adhesion molecules BUTnThese effects may repre

12、sent pleiotropic effects of lipid-modifying agents and be unrelated to the changes in lipoprotein levelsnThe evidence that atherosclerosis is an inflammatory disorder is overwhelmingnLDL are subject to proinflammatory modifications that may account for their atherogenicitynHDL have anti-inflammatory

13、 properties that may contribute to their ability to protect against atherosclerosisnStrategies that reduce proinflammatory modifications to LDL may reduce atherosclerosisnStrategies that increase the anti-inflammatory properties of HDL may also reduce atherosclerosisnMore research is needed to determine whether pharmacological increases in HDL are anti-inflammatory and reduce atherosclerosis谢谢您的聆听与观看THANK YOU FOR YOUR GUIDANCE.感谢阅读！为了方便学习和使用，本文档的内容可以在下载后随意修改，调整和打印。欢迎下载！汇报人：XXX日期：20XX年XX月XX日