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 invivo. However, whether α-tocopherol (vitamin E), an important lipid-soluble antioxidant, is depleted early in atherogenesis and can prevent lipid peroxidation invivo 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 α-tocopherol in studies invitro. Concordant with our previous findings that large amounts of oxidized lipid co-exist with relatively normal α-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 α-tocopherol and the overall content of cis/trans isomers. These data are fully consistent with α-tocopherol acting as a hydrogen donor during lipid oxidation in vivo and suggest that α-tocopherol does not prevent lipoprotein lipid oxidation in the diseased vessel wall.

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