Open AccessIncreased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E
Author(s) -
Yuko Terasawa,
Zuleika Ladha,
Scott W. Leonard,
Jason D. Morrow,
Dale Newland,
David A. Sanan,
Lester Packer,
Maret G. Traber,
Robert V. Farese
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.240462697
Subject(s) - lipid peroxidation , oxidative stress , vitamin e , lesion , medicine , endocrinology , vitamin e deficiency , apolipoprotein e , tocopherol , knockout mouse , aorta , vitamin , apolipoprotein b , biology , antioxidant , biochemistry , pathology , cholesterol , disease , receptor
Although lipid peroxidation in the subendothelial space has been hypothesized to play a central role in atherogenesis, the role of vitamin E in preventing lipid peroxidation and lesion development remains uncertain. Here we show that in atherosclerosis-susceptible apolipoprotein E knockout mice, vitamin E deficiency caused by disruption of the α-tocopherol transfer protein gene (Ttpa ) increased the severity of atherosclerotic lesions in the proximal aorta. The increase was associated with increased levels of isoprostanes, a marker of lipid peroxidation, in aortic tissue. These results show that vitamin E deficiency promotes atherosclerosis in a susceptible setting and support the hypothesis that lipid peroxidation contributes to lesion development.Ttpa −/− mice are a genetic model of vitamin E deficiency and should be valuable for studying other diseases in which oxidative stress is thought to play a role.