EFFECT OF ALPHA-TOCOPHEROL ON RESTENOSIS AFTER ANGIOPLASTY IN A MODELOF EXPERIMENTAL ATHEROSCLEROSIS

The ability of alpha-tocopherol to reduce restenosis after angioplasty was tested in a rabbit model in which angioplasty was performed on es tablished atherosclerotic lesions. Lesions induced by 4 wk of choleste rol feeding after focal desiccation of femoral arteries were balloon d ilated. 3 wk after angioplasty, angiographically determined minimum lu minal diameters were less in the untreated group (0.80+/-0.51 mm) than in the group treated with oral alpha-tocopherol beginning 19 d before angioplasty (1.38+/-0.29 mm; P < 0.01). The cross-sectional area of t he intima-media was greater in the untreated group (1.18+/-0.48 mm(2)) than in the alpha-tocopherol group (0.62+/-0.25 mm(2), P < 0.0001). T hese differences were not due to vasoconstriction or altered plasma ch olesterol. Alpha-tocopherol thus reduced restenosis after angioplasty in this model. In rabbit vascular smooth muscle cells, oxidized low de nsity lipoprotein stimulated DNA synthesis. Alpha-tocopherol treatment inhibited DNA synthesis stimulated by oxidized low density lipoprotei n, but not by serum. The findings are consistent with the hypothesis t hat oxidized lipids can stimulate hyperplasia and that antioxidants ma y limit hyperplasia by inhibiting either the oxidation or the prolifer ative effects of oxidants on cells.