Oxidized lipid accumulates in the presence of alpha-tocopherol in atherosclerosis.
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 in vivo. However, whether alpha-tocopherol (vitamin E), an important lipid-soluble antioxidant, is depleted early in atherogenesis and can prevent lipid peroxidation in vivo 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 alpha-tocopherol in studies in vitro. Concordant with our previous findings that large amounts of oxidized lipid co-exist with relatively normal alpha-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 alpha-tocopherol and the overall content of cis/trans isomers. These data are fully consistent with alpha-tocopherol acting as a hydrogen donor during lipid oxidation in vivo and suggest that alpha-tocopherol does not prevent lipoprotein lipid oxidation in the diseased vessel wall.
Upston
Joanne M
JM
Biochemistry Group, The Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, NSW, 2050, Australia.
Terentis
Andrew C
AC
Morris
Kathryn
K
Keaney Jr
John F
JF
Stocker
Roland
R
D000328:Adult; D000368:Aged; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D013237:Stereoisomerism; D014810:Vitamin E / Q000494:pharmacology*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E