Ashfaq Salman, Abramson Jerome L, Jones Dean P, Rhodes Steven D, Weintraub William S, Hooper W Craig, Vaccarino Viola, Alexander R Wayne, Harrison David G, Quyyumi Arshed A
Division of Cardiology, University of Kansas School of Medicine, Wichita, USA.
Hypertension. 2008 Jul;52(1):80-5. doi: 10.1161/HYPERTENSIONAHA.107.097386. Epub 2008 May 26.
Endothelial dysfunction is known to precede the development of atherosclerosis and results primarily from increased oxidative degradation of NO. We hypothesized that assessment of oxidative stress in the bloodstream will reliably predict endothelial function in healthy adults. A total of 124 healthy nonsmokers had endothelial function assessed using ultrasound measurement of brachial artery flow-mediated vasodilation. Plasma oxidative stress was estimated by measuring the levels of the reduced and oxidized forms of thiols, including glutathione (reduced glutathione and oxidized glutathione) and cysteine (cysteine and cystine), respectively, and the mixed disulfide. Among the traditional risk factors, there were significant and independent correlations between flow-mediated vasodilation and high-density lipoprotein level, body mass index, gender, and the Framingham risk score. Among the thiol markers, plasma cystine (r=-0.23; P=0.009) and the mixed disulfide (r=-0.23; P=0.01) levels correlated with endothelium-dependent but not endothelium-independent vasodilation, even after adjusting for the Framingham risk score and high-sensitivity C-reactive protein level. A higher level of oxidized metabolites was associated with worse endothelial function. In conclusion, the oxidative stress markers, cystine, and the mixed disulfide are independent predictors of endothelial function. These markers, in combination with the Framingham risk score, may help in the early identification of asymptomatic subjects with endothelial dysfunction who are at potentially increased risk for future atherosclerotic disease progression.
已知内皮功能障碍先于动脉粥样硬化的发展,主要是由一氧化氮(NO)氧化降解增加所致。我们推测,评估血流中的氧化应激将可靠地预测健康成年人的内皮功能。共有124名健康非吸烟者通过超声测量肱动脉血流介导的血管舒张来评估内皮功能。血浆氧化应激通过分别测量硫醇的还原形式和氧化形式的水平来估计,包括谷胱甘肽(还原型谷胱甘肽和氧化型谷胱甘肽)和半胱氨酸(半胱氨酸和胱氨酸)以及混合二硫键。在传统危险因素中,血流介导的血管舒张与高密度脂蛋白水平、体重指数、性别和弗雷明汉风险评分之间存在显著且独立的相关性。在硫醇标志物中,即使在调整了弗雷明汉风险评分和高敏C反应蛋白水平后,血浆胱氨酸(r = -0.23;P = 0.009)和混合二硫键(r = -0.23;P = 0.01)水平与内皮依赖性而非内皮非依赖性血管舒张相关。氧化代谢产物水平较高与内皮功能较差有关。总之,氧化应激标志物胱氨酸和混合二硫键是内皮功能的独立预测因子。这些标志物与弗雷明汉风险评分相结合,可能有助于早期识别内皮功能障碍的无症状受试者,这些受试者未来发生动脉粥样硬化疾病进展的风险可能增加。