Macrophages and oxidized low density lipoproteins in the pathogenesis of atherosclerosis.

Oxidized low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. Recent evidence strongly suggests that oxidized LDL is present in atherosclerotic lesions in vivo: 1) LDL isolated from human and rabbit lesions (but not from normal intima) resembles oxidized LDL in its physical, chemical and immunological properties; 2) Oxidized LDL and/or oxidation specific lipid-protein adducts can be demonstrated in human and rabbit lesions by immunocytochemical techniques; 3) Human and rabbit serum contains autoantibodies against oxidized LDL and oxidation specific lipid-protein adducts; 4) atherosclerotic lesions contain IgG that recognizes oxidized LDL and 5) antioxidant therapy slows the development of atherosclerotic lesions in rabbits. Atherosclerosis in human and rabbit arteries may be linked to macrophage-induced oxidative modification of LDL mediated by 15-lipoxygenase which leads to an enhanced uptake of LDL in macrophages by way of the scavenger receptor(s). The identification of LDL oxidation as one of the key events in the early pathogenesis of atherosclerosis offers an interesting possibility to reduce atherosclerosis by antioxidants, enzyme inhibitors and other compounds that protect LDL against oxidative damage and/or reduce the subsequent harmful effects of oxidized LDL on various cellular functions.