Kynurenine, quinolinic acid-The new factors linked to carotid atherosclerosis in patients with end-stage renal disease
Kynurenine, quinolinic acid-The new factors linked to carotid atherosclerosis in patients with end-stage renal disease
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DOI：
10.1016/j.atherosclerosis.2008.10.002
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发表时间：
2009-06-01
期刊：
影响因子：
5.3
通讯作者：
Pawlak, Dariusz
中科院分区：
文献类型：
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作者：
Pawlak, Krystyna;Brzosko, Szymon;Pawlak, Dariusz
在终末期肾病（ESRD）中已报告了氧化应激（SOX）增加、炎症和加速动脉粥样硬化，但其与犬尿氨酸通路激活的相关性仍不清楚。我们测定了犬尿氨酸（KYN）、犬尿烯酸（KYNA）和喹啉酸（QA）的血浆浓度;三种不同的SOX标志物：Cu/Zn超氧化物歧化酶（Cu/Zn SOD）、总过氧化物和丙二醛（MDA）、高敏C反应蛋白（hs CRP）作为炎症指标，内膜中层厚度（IMT）-系统性动脉粥样硬化的早期反映在124例ESRD患者的人群中。在尿毒症中，KYN、KYNA和QA的浓度分别增加了对照值的37- 105%、84- 428%和394-1018%。这些变化伴随着kyna/kyn和qa/kyn比值的显著增加，反映了犬尿氨酸途径酶的活性增加。KYN、QA和qa/kyn比值与尿毒症患者的炎症、SOX标志物和IMT值呈正相关。多元逐步回归分析显示年龄、糖尿病、QA和qa/kyn比值与IMT增加显著相关。总之，本研究的结果表明，犬尿氨酸途径激活和氧化应激增加，炎症和终末期肾病患者动脉粥样硬化的进展之间的关系。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Increased oxidative stress (SOX), inflammation and accelerated atherosclerosis have been reported in end-stage renal disease (ESRD), but their associations with kynurenine pathway activation remain unknown. We determined the plasma concentrations of kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA); three distinct SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD), total peroxide and malondialdehyde (MDA), high sensitivity C-reactive protein (hs CRP) as a indicator of inflammation, and intima-media thickness (IMT)-an early reflection of the systemic atherosclerosis in the population of 124 patients with ESRD. In uraemia, the concentrations of KYN, KYNA and QA were increased by 37-105%, by 84-428%, and by 394-1018% of the control values; respectively. These changes were accompanied by significant increase in kyna/kyn and qa/kyn ratios, reflecting increased activity of kynurenine pathway enzymes. KYN, QA and qa/kyn ratio were positively associated with inflammation, SOX markers, and IMT values in uraemics. Moreover, multiple stepwise regression analysis identified age, presence of diabetes mellitus, QA and qa/kyn ratio as the independent variables significantly associated with increased IMT in this population. In conclusion, the results of the present study suggest a relationship between kynurenine pathway activation and increased oxidative stress, inflammation and the progression of atherosclerosis in end-stage renal disease patients. (C) 2008 Elsevier Ireland Ltd. All rights reserved.