慢性肾脏病中的血管功能障碍、氧化应激和炎症。
Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease.
机构信息
Anschutz Medical Campus, University of Colorado, Aurora, Colorado.
Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado.
出版信息
Kidney360. 2020 Jun;1(6):501-509. doi: 10.34067/kid.0000962019. Epub 2020 Jun 25.
BACKGROUND
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.
METHODS
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 m) 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.
RESULTS
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; <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%; =0.02). Circulating inflammation markers (C-reactive protein and IL-6) were elevated in the CKD group (≤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; =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 =0.04), suggesting vascular oxidative stress could not be overcome with ascorbic acid in participants with CKD.
CONCLUSIONS
Vascular oxidative stress is present in CKD, which cannot be overcome with acute infusion of ascorbic acid.
背景
在患有 CKD 的患者中，动脉僵硬度增加和血管内皮功能障碍是重要的非传统心血管危险因素。血管氧化应激和炎症可能导致 CKD 中的血管功能障碍，但缺乏直接证据。
方法
我们评估了中重度 CKD（eGFR 为 15-59 ml/min/1.73 m）患者和健康对照组的颈股脉搏波速度（动脉僵硬度）和肱动脉血流介导的扩张（血管内皮功能）。还测量了急性给予抗坏血酸抑制血管氧化应激（与生理盐水相比）后肱动脉血流介导的扩张的变化。还从外周静脉采集血管内皮细胞的蛋白表达，并进行 ELISA 以评估循环标志物。
结果
共纳入 64 名 CKD 患者（平均±标准差，65±8 岁）和 17 名健康对照者（60±5 岁）。与健康对照组相比，CKD 患者的颈股脉搏波速度更高（1071±336 对 732±128 cm/s；<0.001）。与健康对照组相比，CKD 患者的肱动脉血流介导的扩张较低（3.5%±2.8%对 5.5%±3.2%；=0.02）。CKD 组循环炎症标志物（C 反应蛋白和 IL-6）升高（≤0.02）。与健康对照组相比，CKD 患者的内皮细胞 NADPH 蛋白表达（强度与人类脐静脉内皮细胞对照相比，1.48±0.28 对 1.25±0.31；=0.05）更高。然而，抗坏血酸可显著改善对照组患者的肱动脉血流介导的扩张（生理盐水，5.5±3.2；抗坏血酸，6.8±3.6）；与 CKD 患者相比（生理盐水，3.5±2.8；抗坏血酸，3.6±3.2）（组×条件交互作用=0.04），表明在 CKD 患者中，抗坏血酸不能克服血管氧化应激。
结论
CKD 中存在血管氧化应激，急性输注抗坏血酸无法克服。
Zotero 插件