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
相关论文
共 117 条
  • [31] Hiramatsu, Rosen, Heinecke, Wolfbauer, Chait, Superoxide initiates oxidation of low density lipoprotein by human monocytes, Arteriosclerosis, 7, pp. 55-60, (1987)
  • [32] Cathcart, Chisolm, McNally, Morel, Oxidation modification of low density lipoprotein by activated human monocytes and the cell lines U937 and HL60, In Vitro Cell. Dev. Biol., 24, pp. 1001-1008, (1988)
  • [33] Cathcart, McNally, Morel, Chisolm, Superoxide anion participation in human monocyte-mediated oxidation of low-density lipoprotein and conversion of low-density lipoprotein to a cytotoxin, J. Immunol., 142, pp. 1963-1969, (1989)
  • [34] Bedwell, Dean, Jessup, The action of defined oxygen-centered free radicals on human low-density lipoprotein, Biochem. J., 262, pp. 707-712, (1989)
  • [35] Parthasarathy, Wieland, Steinberg, A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein, Proc. Natl. Acad. Sci. USA, 86, pp. 1046-1050, (1989)
  • [36] Heinecke, Rosen, Suzuki, Chait, The role of sulfur-containing amino acids in superoxide production by arterial smooth muscle cells, J Biol Chem, 262, pp. 10098-10103, (1987)
  • [37] Parthasarthy, Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor, Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 917, pp. 337-340, (1987)
  • [38] Heinecke, Rosen, Chait, Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture, J. Clin. Invest., 74, pp. 1890-1894, (1984)
  • [39] Esterbauer, Jurgens, Quehenberger, Koller, Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes, J. Lipid Res., 28, pp. 495-509, (1987)
  • [40] Quintao, Witztum, Parthasarathy, Elam, Steinberg, Role of β-carotene in the oxidative modification of low density lipoproteins, Arteriosclerosis, 9, (1989)