NEW ROLES OF LOW-DENSITY LIPOPROTEINS AND VITAMIN-E IN THE PATHOGENESIS OF ATHEROSCLEROSIS

Accumulation of oxidized low density lipoproteins in macrophages and s mooth muscle cells causes foam cell formation, an initial step in athe rosclerosis. Active oxygen species are considered important in the pat hogenesis of the disease. Antioxidants, such as tocopherols and tocotr ienols have been considered to prevent the deleterious effects of acti ve oxygen species. We found native low density lipoproteins can stimul ate directly smooth muscle cell proliferation, it is associated with a n increase of protein kinase C activity. d-alpha-Trocopherol, biologic ally most active form of vitamin E, inhibits both cell proliferation a nd protein kinase C activity. The effect of d-alpha-tocopherol is not related to its radical scavenging properties. Transforming growth fact or-beta secreted by smooth muscle cells as growth inhibitor. Low densi ty lipoproteins decrease the release of transforming growth factor-bet a from smooth muscle cells thus activating growth. d-alpha-Tocopherol activates the cellular release of transforming growth factor-beta. The se new aspects explain the important role of low density lipoproteins and vitamin E in increasing and decreasing the risk of atherosclerosis , respectively.