The role of free radicals as mediators of endothelial cell injury in hyperhomocysteinemia.
Hyperhomocysteinemia has been suggested as a potent new risk factor for premature cardiovascular disease. Homocsyteine can induce endothelial cell injury but the mechanism is not understood. The purpose of this study was to evaluate the role of free radicals as potential causes of endothelial cell injury in a case-control study of obligate heterozygotes for cystathionine beta-synthase deficiency. Firstly, free radical production as measured by neutrophil chemiluminescence in obligate heterozygotes for cystathionine beta-synthase deficiency was compared with age- and sex-matched normal subjects. Secondly, the response of the cellular antioxidant system was examined by measuring the enzymes superoxide dismutase and glutathione peroxidase, their cofactors (selenium, copper), vitamin E and vitamin A in heterozygotes and normal subjects. Analyses of neutrophil chemiluminescence, vitamin A and E, glutathione peroxidase, selenium and copper showed no difference between heterozygotes and controls. While superoxide dismutase activity was higher in heterozygotes than normal subjects, the difference did not reach statistical significance and the hypothesis of excess free radical production as a mechanism of injury was not confirmed. However, further examination of superoxide dismutase activity in a larger number of subjects would be of interest.
Clarke
R
R
Department of Cardiology, Adelaide Hospital, Dublin.
Naughten
E
E
Cahalane
S
S
Sullivan
K O
KO
Mathias
P
P
McCall
T
T
Graham
I
I
D000328:Adult; D016022:Case-Control Studies; D003541:Cystathionine beta-Synthase / Q000172:deficiency*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000378:metabolism
D005609:Free Radicals; D006710:Homocysteine; D003541:Cystathionine beta-Synthase