Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits

Oxidized low-density lipoproteins (LDL) are implicated in atherosclerosis. However, large-scale intervention studies designed to test whether antioxid ants, such as vitamin E, can ameliorate cardiovascular disease have generat ed ambivalent results. This may relate to the fact that the mechanism where by lipid oxidation is initiated in vivo is unknown and the lack of direct e vidence for a deficiency of antioxidants in atherosclerotic lesions. Furthe r, there is little evidence to suggest that vitamin E acts as an antioxidan t for lipid peroxidation in vivo. Here we tested the antioxidant effect of dietary vitamin E (alpha -tocopherol) supplementation on intimal proliferat ion and lipid oxidation in balloon-injured, hypercholesterolemic rabbits. a lpha -Tocopherol supplementation increased vascular content of alpha -tocop herol over 30-fold compared to nonsupplemented and alpha -tocopherol-defici ent chows. Balloon injury resulted in oxidized lipid deposition in the aort a. Maximum levels of primary lipid oxidation products, measured as hydroper oxides of esterified lipid (LOOH) and oxidized linoleate (HODE), were 0.22 and 1.10 nmol/mg, representing 0.21 and 0.39% of the precursor molecule, re spectively. Secondary lipid oxidation products, measured as oxysterols, wer e maximal at 5.60 nmol/mg or 1.48% of the precursor compound. Vascular HODE and oxysterols were significantly reduced by vitamin E supplementation. Ho wever, the intima/media ratio of aortic vessels increased with vitamin E su pplementation, suggesting that the antioxidant promoted intimal proliferati on, Thus, the study demonstrates a dissociation of aortic lipid oxidation a nd lesion development, and suggests that vitamin E does not prevent lesion development in this animal model. (C) 2001 Elsevier Science Inc.