Increased atherosclerosis in hyperlipidemic mice deficient in alpha-tocopherol transfer protein and vitamin E

Although lipid peroxidation in the subendothelial space has been hypothesiz ed to play a central role in atherogenesis, the role of vitamin E in preven ting lipid peroxidation and lesion development remains uncertain. Here we s how that in atherosclerosis-susceptible apolipoprotein E knockout mice, vit amin E deficiency caused by disruption of the alpha -tocopherol transfer pr otein gene (Ttpa) increased the severity of atherosclerotic lesions in the proximal aorta. The increase was associated with increased levels of isopro stanes, a marker of lipid peroxidation, in aortic tissue. These results sho w that vitamin E deficiency promotes atherosclerosis in a susceptible setti ng and support the hypothesis that lipid peroxidation contributes to lesion development. Ttpa(-/-) mice are a genetic model of vitamin E deficiency an d should be valuable for studying other diseases in which oxidative stress is thought to play a role.