ANTI-ATHEROGENIC EFFECTS OF ANTIOXIDANTS
The difficulty in linking inhibition of LDL oxidation with inhibition of atherosclerosis ma. stem from the dynamic nature of CRD, CRD involves not only the development of ar. atherosclerotic plaque, but also plaque rupture, vasoconstriction, and local thrombosis, resulting in partial or total arterial obstruction. Some antioxidants may limit the clinical expression of atherosclerosis by stabilizing the plaque rather than by affecting its size. Scavenger recepto~ activity has been shown to be downregulated in macrophages after incubation with a-tocophero Several other mechanisms can contribute to the vascular effects of a-tocopherol: it has beel: shown to reduce monocyte adhesion and transmigration into the intima, it can inhibit thE: proliferation of smooth muscle cells, and it prevents the cytotoxic effects of oxidized LDL b. reducing endothelial cell damage. Oxidized LDL also impairs the release of nitric oxide froIr. normal arteries, which usually prevents inappropriate adhesion of leukocytes and platelets and vasospasm.
Thus, the presence of oxidized LDL might contribute to the platelet adhesion an vasospasm that are involved in, the pathogenesis of acute coronary syndromes. LDL derive from patients treated with Probucol (a synthetic antioxidant) and oxidized in vitro does no· impair the action of nitric oxide to the same degree as LDL derived from normal subjects Antioxidant protection of LDL by Probucol and improved endothelial function has also been found in patients treated for hypercholesterolemia. These alternative vascular effects of antioxidants and decreased LDL oxidation may explain the positive findings for antioxidants in the prevention of secondary CRD or the clinical expression of established CRD, rathe than in primary prevention or the initial development of atherosclerotic lesions.
