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Glutathione Articles - Cardiovascular Disease
The relationship between plasma levels of oxidized and reduced thiols
and early atherosclerosis in healthy adults
Ashfaq S, Abramson JL, Jones DP, Rhodes SD,
Weintraub WS, Hooper WC, Vaccarino V, Harrison DG, Quyyumi AA
J Am Coll Cardiol. 2006 Mar 7;47(5):1005-11. Epub 2006 Feb 9.
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ABSTRACT
OBJECTIVES: The study
investigated the relationship between biomarkers of oxidative stress and
early atherosclerosis. BACKGROUND: Oxidative stress is an important
etiologic factor in the pathogenesis of vascular disease. We
hypothesized that oxidative stress would predict early atherosclerosis
in a relatively healthy population.
METHODS: One hundred fourteen healthy non-smokers, without known
clinical atherosclerosis, had carotid intima-media thickness (IMT)
measured using ultrasound. Oxidative stress was estimated by measuring
plasma levels of: 1) glutathione (GSH), an important intracellular
antioxidant thiol, its oxidized disulfide form (GSSG), and their redox
state (E(h) GSH/GSSG), and 2) cysteine (Cys), an important extracellular
antioxidant thiol, its oxidized disulfide form cystine (CySS), and their
redox state (E(h)Cys/CySS).
RESULTS: The univariate predictors of IMT were age, body mass index,
low-density lipoprotein cholesterol, triglycerides, high-density
lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP),
and Framingham risk score. Intima-media thickness was also higher in
males and hypertensive subjects. Among the oxidative stress markers, GSH
(r = -0.39, p < 0.0001), CySS (r = 0.18, p = 0.049), and E(h) GSH/GSSG
(r = 0.34, p < 0.0002) correlated with IMT. After adjusting for
traditional risk factors and hs-CRP, only E(h) GSH/GSSG remained an
independent predictor of IMT. E(h) GSH/GSSG predicted IMT in a manner
that was both independent of and additive to Framingham risk score.
CONCLUSIONS: Glutathione redox state (E(h) GSH/GSSG), an in vivo measure
of intracellular oxidative stress, is an independent predictor for the
presence of early atherosclerosis in an otherwise healthy population.
This finding supports a role for oxidative stress in the pathogenesis of
premature atherosclerosis, and its measurement may help in the early
identification of asymptomatic subjects at risk of atherosclerotic
disease.
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