Increased atherosclerosis in hyperlipidemic mice deficient in alpha -tocopherol transfer protein and vitamin E.
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 alpha-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.
Terasawa
Y
Y
Gladstone Institute of Cardiovascular Disease, P. O. Box 419100, San Francisco, CA 94141-9100, USA.
Ladha
Z
Z
Leonard
S W
SW
Morrow
J D
JD
Newland
D
D
Sanan
D
D
Packer
L
L
Traber
M G
MG
Farese
R V
RV
D000818:Animals; D001161:Arteriosclerosis / Q000150:complications* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D006949:Hyperlipidemias / Q000150:complications* / Q000235:genetics; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014811:Vitamin E Deficiency / Q000150:complications*
D002352:Carrier Proteins; D017931:DNA Primers; C017763:alpha-tocopherol transfer protein