Protective effect of vitamin E supplements on experimental atherosclerosis is modest and depends on preexisting vitamin E deficiency.
Vitamin E has failed to protect humans from cardiovascular disease outcome, yet its role in experimental atherosclerosis remains less clear. A previous study (Proc. Natl. Acad. Sci. USA 97:13830-13834; 2000) showed that vitamin E deficiency caused by disruption of the alpha-tocopherol transfer protein gene (Ttpa) is associated with a modest increase in atherosclerosis in apolipoprotein E gene deficient (Apoe(-/-)) mice. Here we confirm this finding and report that in Apoe(-/-)Ttpa(-/-) mice dietary alpha-tocopherol (alphaT) supplements restored circulating and aortic levels of alphaT, and decreased atherosclerosis in the aortic root to a level comparable to that seen in Apoe(-/-) mice. However, such dietary supplements did not decrease disease in Apoe(-/-) mice, whereas dietary supplements with a synthetic vitamin E analog (BO-653), either alone or in combination with alphaT, decreased atherosclerosis in Apoe(-/-) and in Apoe(-/-)Ttpa(-/-) mice. Differences in atherosclerosis were not associated with changes in the arterial concentrations of F(2)-isoprostanes and cholesterylester hydro(pero)xides, nor were they reflected in the resistance of plasma lipids to ex vivo oxidation. These results show that vitamin E at best has a modest effect on experimental atherosclerosis in hyperlipidemic mice, and only in situations of severe vitamin E deficiency and independent of lipid oxidation in the vessel wall.
Suarna
Cacang
C
Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Wu
Ben J
BJ
Choy
Katherine
K
Mori
Trevor
T
Croft
Kevin
K
Cynshi
Osamu
O
Stocker
Roland
R
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D001572:Benzofurans / Q000494:pharmacology; D019587:Dietary Supplements; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D014451:Ubiquinone / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency; D024502:alpha-Tocopherol / Q000378:metabolism
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D001057:Apolipoproteins E; D001572:Benzofurans; D008074:Lipoproteins; D014451:Ubiquinone; D014810:Vitamin E; D024502:alpha-Tocopherol; D010100:Oxygen