LDL oxidation by arterial wall macrophages depends on the oxidative status in the lipoprotein and in the cells: role of prooxidants vs. antioxidants.
Oxidized LDL is highly atherogenic as it stimulates macrophage cholesterol accumulation and foam cell formation, it is cytotoxic to cells of the arterial wall and it stimulates inflammatory and thrombotic processes. LDL oxidation can lead to its subsequent aggregation, which further increases cellular cholesterol accumulation. All major cells in the arterial wall including endothelial cells, smooth muscle cells and monocyte derived macrophages can oxidize LDL. Macrophage-mediated oxidation of LDL is probably a hallmark in early atherosclerosis, and it depends on the oxidative state of the LDL and that of the macrophages. The LDL oxidative state is elevated by increased ratio of poly/mono unsaturated fatty acids, and it is reduced by elevation of LDL-associated antioxidants such as vitamin E, beta-carotene, lycopene, and polyphenolic flavonoids. The macrophage oxidative state depends on the balance between cellular NADPH-oxidase and the glutathione system. LDL-associated polyphenolic flavonoids which inhibit its oxidation, can also reduce macrophage oxidative state, and subsequently the cell-mediated oxidation of LDL. Oxidation of the macrophage lipids, which occurs under oxidative stress, can lead to cell-mediated oxidation of LDL even in the absence of transition metal ions, and may be operable in vivo. Finally, elimination of Ox-LDL from extracellular spaces, after it was formed under excessive oxidative stress, can possibly be achieved by the hydrolytic action of HDL-associated paraoxonase on lipoprotein's lipid peroxides. The present review article summarizes the above issues with an emphasis on our own data.
Aviram
M
M
Lipid Research Laboratory, Technion Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
Fuhrman
B
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects
D000975:Antioxidants; D008077:Lipoproteins, LDL; D016877:Oxidants; C099252:oxidized low density lipoprotein