Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.
Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.
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DOI：
10.34067/kid.0000962019
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发表时间：
2020-06
期刊：
影响因子：
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通讯作者：
Chonchol M
中科院分区：
文献类型：
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作者：
Nowak KL;Jovanovich A;Farmer-Bailey H;Bispham N;Struemph T;Malaczewski M;Wang W;Chonchol M
动脉僵硬度增加和血管内皮功能障碍是 CKD 患者明显的重要非传统心血管危险因素。血管氧化应激和炎症可能导致 CKD 血管功能障碍，但缺乏直接证据。我们评估了中重度 CKD 参与者（eGFR 15-59 ml/min/1.73 m2）和健康对照的颈动脉脉搏波速度（动脉僵硬度）和肱动脉血流介导的扩张（血管内皮功能）。还测量了急性输注抗坏血酸以抑制血管氧化应激（与盐水相比）后肱动脉血流介导的扩张的变化。还进行了从外周静脉收集的血管内皮细胞的蛋白质表达和用于评估循环标记物的ELISA。总共包括 64 名 CKD 参与者（平均值±SD，65±8 岁）和 17 名健康对照者（60±5 岁）。与健康对照相比，CKD 参与者的颈动脉-股动脉脉搏波速度更大（1071±336 与 732±128 cm/s；P<0.001）。与健康对照相比，CKD 参与者的肱动脉血流介导的扩张较低（3.5%±2.8% 对比 5.5%±3.2%；P=0.02）。 CKD 组循环炎症标志物（C 反应蛋白和 IL-6）升高（P≤0.02）。 CKD 参与者的 NADPH 内皮细胞蛋白表达（强度与人脐静脉内皮细胞对照相比，1.48±0.28 与 1.25±0.31；P=0.05）较高。然而，抗坏血酸显着改善了对照参与者的肱动脉血流介导的扩张（盐水，5.5±3.2；抗坏血酸，6.8±3.6）；与 CKD 参与者相比（生理盐水，3.5±2.8；抗坏血酸，3.6±3.2）（组×条件交互作用 P=0.04），表明 CKD 参与者抗坏血酸不能克服血管氧化应激。 CKD 中存在血管氧化应激，无法通过急性输注抗坏血酸来克服。
Increased arterial stiffness and vascular endothelial dysfunction are important nontraditional cardiovascular risk factors evident in patients with CKD. Vascular oxidative stress and inflammation may contribute to vascular dysfunction in CKD, but direct evidence is lacking. We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with moderate-to-severe CKD (eGFR 15–59 ml/min per 1.73 m2) and in healthy controls. Change in brachial artery flow-mediated dilation after an acute infusion of ascorbic acid to inhibit vascular oxidative stress (versus saline) was also measured. Protein expression of vascular endothelial cells collected from a peripheral vein and ELISAs to assess circulating markers were also performed. A total of 64 participants with CKD (mean±SD, 65±8 years) and 17 healthy controls (60±5 years) were included. Carotid-femoral pulse-wave velocity was greater in participants with CKD compared with healthy controls (1071±336 versus 732±128 cm/s; P<0.001). Brachial artery flow-mediated dilation was lower in participants with CKD compared with healthy controls (3.5%±2.8% versus 5.5%±3.2%; P=0.02). Circulating inflammation markers (C-reactive protein and IL-6) were elevated in the CKD group (P≤0.02). Endothelial cell protein expression of NADPH (intensity versus human umbilical vein endothelial cell control, 1.48±0.28 versus 1.25±0.31; P=0.05) was greater in participants with CKD. However, ascorbic acid significantly improved brachial artery flow-mediated dilation in control participants (saline, 5.5±3.2; ascorbic acid, 6.8±3.6); as compared with participants with CKD (saline, 3.5±2.8; ascorbic acid, 3.6±3.2) (group×condition interaction P=0.04), suggesting vascular oxidative stress could not be overcome with ascorbic acid in participants with CKD. Vascular oxidative stress is present in CKD, which cannot be overcome with acute infusion of ascorbic acid.