Oxidized lipid accumulates in the presence of alpha-tocopherol in atherosclerosis.

Oxidative modification of low-density lipoproteins in the arterial wall is a key feature of atherogenesis and widely believed to cause and/or accelerate lesion development. Linked to this is the expectation that vascular antioxidants are depleted during oxidation in vivo. However, whether alpha-tocopherol (vitamin E), an important lipid-soluble antioxidant, is depleted early in atherogenesis and can prevent lipid peroxidation in vivo is unresolved. To address this we examined the content of specific configurational isomers (cis/trans) of lipid hydro(pero)xides in lesions, which represent the major non-enzymic oxidation products, as formation and accumulation of cis/trans isomers is influenced by alpha-tocopherol in studies in vitro. Concordant with our previous findings that large amounts of oxidized lipid co-exist with relatively normal alpha-tocopherol levels in human lesions, we now show that cis/trans isomers predominate over other products in human carotid and aortic lesions and in lesion lipoproteins. Further, dietary vitamin E supplementation of rabbits after arterial injury significantly increases both the aortic levels of alpha-tocopherol and the overall content of cis/trans isomers. These data are fully consistent with alpha-tocopherol acting as a hydrogen donor during lipid oxidation in vivo and suggest that alpha-tocopherol does not prevent lipoprotein lipid oxidation in the diseased vessel wall.