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 cholest erol accumulation and foam cell formation, it is cytotoxic to cells of the arterial wall and it stimulates inflammatory and thrombotic proce sses. LDL oxidation can lead to its subsequent aggregation, which furt her increases cellular cholesterol accumulation. All major cells in th e arterial wall including endothelial cells, smooth muscle cells and m onocyte derived macrophages can oxidize LDL. Macrophage-mediated oxida tion of LDL is probably a hallmark in early atherosclerosis, and it de pends on the oxidative state of the LDL and that of the macrophages. T he LDL oxidative state is elevated by increased ratio of poly/mono uns aturated fatty acids, and it is reduced by elevation of LDL-associated antioxidants such as vitamin E, beta-carotene, lycopene, and polyphen olic flavonoids. The macrophage oxidative state depends on the balance between cellular NADPH -oxidase and the glutathione system. LDL-assoc iated polyphenolic flavonoids which inhibit its oxidation, can also re duce macrophage oxidative state, and subsequently the cell-mediated ox idation 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. Fin ally elimination of Ox-LDL from extracellular spaces, after it was for med under excessive oxidative stress, can possibly be achieved by the hydrolytic action of I-IDL-associated paraoxonase on lipoprotein's lip id peroxides. The present review article summarizes the above issues w ith an emphasis on our own data.