The role of alpha-tocopherol in preventing disease.
A role of oxidative stress in atherosclerosis lies on experimental results carried out in vitro and in animal models. In humans, the supplementation with the antioxidant vitamin E has given in some cases supportive results and in others no effects. From in vitro studies, a large amount of data has shown that alpha-tocopherol (the major component of vitamin E) regulates key events in the cellular pathogenesis of atherosclerosis. We first described the inhibition of protein kinase C (PKC) activity by alpha-tocopherol to be at the basis of the vascular smooth muscle cell growth inhibition by this compound. Subsequently, PKC was recognized to be the target of alpha-tocopherol in different cell types, including monocytes, macrophages, neutrophils, fibroblasts and mesangial cells. Inhibiting the activity of protein kinase C by alpha-tocopherol results in different events in different cell types: inhibition of platelet aggregation, of nitric oxide production in endothelial cells, of superoxide production in neutrophils and macrophages as well as impairment of smooth muscle cell proliferation. Adhesion molecule expression and inflammatory cell cytokine production are also influenced by alpha-tocopherol. Scavenger receptors, particularly important in the formation of atherosclerotic foam cells, are also modulated by alpha-tocopherol. The oxidized LDL scavenger receptors SR-A and CD36 are down regulated at the transcriptional level by alpha-tocopherol. The relevance of CD36 expression in the onset of atherosclerosis has been indicated by the protection against atherosclerosis by CD36 knockout mice. In conclusion, the effect of alpha-tocopherol against atherosclerosis is not due only to the prevention of LDL oxidation but also to the down regulation of the scavenger receptor CD36 and to the inhibition of PKC activity.
Azzi
Angelo
A
Institut für Biochemie und Molekularbiologie, Universität Bern, Bühlstrasse 28, 3012 Bern, Switzerland. angelo.azzi@mci.unibe.ch
D000818:Animals; D000975:Antioxidants; D001158:Arteries / Q000000981:diagnostic imaging; D001161:Arteriosclerosis / Q000517:prevention & control; D018849:Controlled Clinical Trials as Topic; D004032:Diet; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011315:Preventive Medicine; D014463:Ultrasonography; D014810:Vitamin E / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D000975:Antioxidants; D014810:Vitamin E; D024502:alpha-Tocopherol