ROLE OF OXIDATIVELY MODIFIED LDL IN ATHEROSCLEROSIS

被引:572
作者
STEINBRECHER, UP
ZHANG, HF
LOUGHEED, M
机构
基金
英国医学研究理事会;
关键词
Aterosclerosis; Free radicals; Lipid peroxidation; Macrophages; Oxidized LDL; Scavenger receptor;
D O I
10.1016/0891-5849(90)90119-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative modification of LDL is accompanied by a number of compositional and structural changes, including increased electrophoretic mobility, increased density, fragmentation of apolipoprotein B, hydrolysis of phosphatidylcholine, derivatization of lysine amino groups, and generation of lfuorescent adducts due to covalent binding of lipid oxidation products to apo B. In addition, oxidation of LDL has been shown to result in numerous changes in its biologic properties that could have pathogenetic imortance, including accelerated uptake in macrophages, cytotoxicity, and chemotactic activity for monocytes. The present article summarrizes very recent developments related to the mechanism of oxidation of LDL by cells, receptor-mediated uptake of oxidized LDL in macrophages, the mechanism of phosphatidylcholine hydrolysis during LDL oxidation, and other biologic actions of oxidized LDL including cytotoxicity, altered eicosanoid metabolism, and effects on the secretion of growth factors and chemotactic factors. In addition, this review will exzmine the evidence for the presence of oxidized LDL in vivo and the evidence that oxidized LDL plays a pathogenetic role in atherosclerosis. © 1990.
引用
收藏
页码:155 / 168
页数:14
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  • [1] Fowler, Shio, Haley, Characterization of lipid-laden aortic cells from choleterol-fed rabbits. IV. Investigation of macrophage-like properties of aortic cell populations, Lab. Invest., 4, pp. 372-378, (1979)
  • [2] Schaffner, Taylor, Bartucci, Fischer-Dzoga, Beenson, Glagov, Wissler, Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages, Am. J. Pathol., 100, pp. 57-80, (1980)
  • [3] Gerrity, The role of the monocyte in atherogenesis. I. Transition of blood-borne monocytes into foam cells in fatty lesions, Am. J. Pathol., 1-3, pp. 181-190, (1981)
  • [4] Gerrity, The role of the monocyte in atherogenesis. II. Migration of foam cells from atherosclerotic lesions, Am. J. Pathol., 103, pp. 191-200, (1981)
  • [5] Faggiotto, Ross, Harker, Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation, Arteriosclerosis, 4, pp. 323-340, (1984)
  • [6] Aqel, Ball, Waldman, Mitchinson, Monocytic origin of foam cells in human atherosclerotic plaques, Atherosclerosis, 53, pp. 265-271, (1984)
  • [7] Rosenfield, Tsukuda, Gown, Ross, Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits, Arteriosclerosis, 7, pp. 9-23, (1987)
  • [8] Goldstein, Ho, Basu, Brown, Binding site on macrophages that mediates the uptake and degradation of actylated low density lipoprotein, producing massive cholesterol deposition, Proc. Natl. Acad. Sci. USA, 76, pp. 333-337, (1979)
  • [9] Brown, Basu, Falck, Ho, Goldstein, The scavenger cell pathway for lipoprotein degration: specificity of the binding site that mediates the uptake of negatively charged LDL by macrophages, J. Supramol. Struct., 13, pp. 67-81, (1980)
  • [10] Brown, Goldstein, Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in the macrophage: implications for cholesterol deposition in atherosclerosis, Ann. Rev. Biochem., 52, pp. 223-261, (1983)