Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers.
Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants affect these plasma factors in chronic smokers. In a randomized double-blind placebo-controlled study involving 128 male normolipidemic chronic smokers the effect of a 2-year alpha-tocopherol treatment (400 IU dL-alpha-tocopherol daily) on plasma levels of sICAM-1 and autoantibodies against oxLDL was evaluated. In addition, we monitored production of superoxide by leukocytes ex vivo. It was found that compared to nonsmokers (n = 33) plasma levels of IgG but not IgM autoantibodies against oxLDL and concentrations of sICAM-1 in smokers were significantly elevated (30 and 42%, respectively). After supplementation with alpha-tocopherol concentration of TBARS in plasma and in vitro oxidizability of LDL had decreased, but autoantibodies and sICAM-1 had not changed. Production of superoxide was not different between alpha-tocopherol- and placebo-treated smokers. It is concluded that in chronic smokers, long-term treatment with alpha-tocopherol does not normalize the raised levels of sICAM-1 and autoantibodies against oxLDL, both risk factors for initiation or progression of cardiovascular disease, despite a decrease in in vitro oxidizability of LDL.
van Tits
L J
LJ
Department of Medicine, Division of General Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands. B.vantits@aig.azn.nl
de Waart
F
F
Hak-Lemmers
H L
HL
van Heijst
P
P
de Graaf
J
J
Demacker
P N
PN
Stalenhoef
A F
AF
D000368:Aged; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D001323:Autoantibodies; D008078:Cholesterol, LDL; D003574:Cytochrome c Group; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E