The Bilirubin-Increasing Drug Atazanavir Improves Endothelial Function in Patients With Type 2 Diabetes Mellitus
The Bilirubin-Increasing Drug Atazanavir Improves Endothelial Function in Patients With Type 2 Diabetes Mellitus
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DOI：
10.1161/atvbaha.110.211789
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发表时间：
2011-02-01
影响因子：
8.7
通讯作者：
Smits, Paul
中科院分区：
文献类型：
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作者：
Dekker, Douwe;Dorresteijn, Mirrin J.;Smits, Paul
2型糖尿病（T2 DM）患者，氧化应激导致内皮功能障碍。胆红素是一种强大的内源性抗氧化剂，在临床前实验中可显著减轻内皮功能障碍。吉尔伯特综合征伴有轻度和终身的高胆红素血症，并且仅与通常心血管死亡风险的三分之一相关。阿扎那韦治疗引起的高胆红素血症与吉尔伯特综合征非常相似。因此，我们假设阿扎那韦治疗可以改善氧化应激和血管炎症，改善T2 DM患者的内皮功能。方法和结果-在一项双盲、安慰剂对照的交叉设计中，我们通过阿扎那韦治疗3天诱导16例T2 DM患者出现中度高胆红素血症。第四天，通过静脉闭塞体积描记法评估内皮功能。分别通过动脉内灌注乙酰胆碱和硝酸甘油评估内皮依赖性和内皮非依赖性血管舒张。阿扎那韦治疗诱导平均胆红素水平从7 μ mol/L（0.4 mg/dL）升高至64 μ mol/L（3.8 mg/dL）。血浆抗氧化能力显著提高（P
Objective-In type 2 diabetes mellitus (T2DM), oxidative stress gives rise to endothelial dysfunction. Bilirubin, a powerful endogenous antioxidant, significantly attenuates endothelial dysfunction in preclinical experiments. The Gilbert syndrome is accompanied by a mild and lifelong hyperbilirubinemia and associated with only one third of the usual cardiovascular mortality risk. The hyperbilirubinemia caused by atazanavir treatment closely resembles the Gilbert syndrome. We thus hypothesized that treatment with atazanavir would ameliorate oxidative stress and vascular inflammation and improve endothelial function in T2DM.Methods and Results-In a double-blind, placebo-controlled crossover design, we induced a moderate hyperbilirubinemia by a 3-day atazanavir treatment in 16 subjects experiencing T2DM. On the fourth day, endothelial function was assessed by venous occlusion plethysmography. Endothelium-dependent and endothelium-independent vasodilation were assessed by intraarterial infusion of acetylcholine and nitroglycerin, respectively. Atazanavir treatment induced an increase in average bilirubin levels from 7 mu mol/L (0.4 mg/dL) to 64 mu mol/L (3.8 mg/dL). A significant improvement in plasma antioxidant capacity (P