Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects.
OBJECTIVE
In a combination of in vivo and in vitro studies, we investigated mechanisms via which alpha-tocopherol, a lipid soluble form of vitamin E, can directly affect endothelial activation as induced by H(2)O(2) and TNFalpha.


METHODS
We measured effects of alpha-tocopherol on H(2)O(2)-induced lipid peroxidation as determined with a fluorescent C-11 BODIPY(581/591) probe and on adhesion molecule expression in cultured endothelial cells. In 20 healthy volunteers treated with increasing doses of alpha-tocopherol up to 800 IU/ml for 12 weeks, plasma levels of soluble cell adhesion molecules (sCAMs) and C-reactive protein were measured.


RESULTS
We showed that alpha-tocopherol protects cultured endothelial cells against H(2)O(2)-induced lipid peroxidation, while TNFalpha did not induce lipid peroxidation. Moreover, alpha-tocopherol attenuated H(2)O(2)-, but not TNFalpha-induced increases in adhesion molecule expression. In healthy persons, alpha-tocopherol decreased plasma levels of sE-selectin from 65+/-6 to 60+/-6 ng/ml (P=0.002), sVCAM from 893+/-31 to 853+/-23 ng/ml (P=0.022), and sICAM from 483+/-21 to 463+/-16 ng/ml (P=0.048). C-Reactive protein, as a sensitive marker of low grade inflammation, was not significantly affected.


CONCLUSIONS
alpha-Tocopherol specifically inhibits lipid peroxidation-induced endothelial activation in vitro. The observed vitamin E-induced decrease in sCAMs in control subjects suggests that lipid peroxidation can take place in healthy individuals. Although vitamin E supplementation may be especially effective in specific groups of patients exposed to increased oxidative stress, our study suggests that vitamin E supplementation can be of benefit in healthy individuals as well.
van Dam
Bastiaan
B
Department of Internal Medicine and Institute for Cardiovascular Research, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
van Hinsbergh
Victor W M
VW
Stehouwer
Coen D A
CD
Versteilen
Amanda
A
Dekker
Henk
H
Buytenhek
Rien
R
Princen
Hans M
HM
Schalkwijk
Casper G
CG
D000975:Antioxidants / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol