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晚期糖基化终产物的血管效应:作为慢性肾病无症状患者动脉钙化和心血管风险预测指标的桡动脉样本中免疫组化检测的晚期糖基化终产物含量

Vascular effects of advanced glycation end-products: content of immunohistochemically detected AGEs in radial artery samples as a predictor for arterial calcification and cardiovascular risk in asymptomatic patients with chronic kidney disease.

作者信息

Janda Katarzyna, Krzanowski Marcin, Gajda Mariusz, Dumnicka Paulina, Jasek Ewa, Fedak Danuta, Pietrzycka Agata, Kuźniewski Marek, Litwin Jan A, Sułowicz Władysław

机构信息

Chair and Department of Nephrology, Jagiellonian University Medical College, Cracow, Poland.

Chair and Department of Histology, Jagiellonian University Medical College, Cracow, Poland.

出版信息

Dis Markers. 2015;2015:153978. doi: 10.1155/2015/153978. Epub 2015 Mar 17.

Abstract

OBJECTIVES

Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters.

MATERIALS AND METHODS

The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified.

RESULTS

Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient's age.

CONCLUSIONS

The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

摘要

目的

我们的目的是确定晚期糖基化终产物(AGEs)的血管沉积是否与慢性肾脏病(CKD)患者的动脉钙化和心血管死亡率相关,并评估AGEs的血管含量与选定的临床和生化参数之间的关系。

材料与方法

该研究纳入了54例CKD患者(33例接受血液透析,21例未透析)。检查参数包括体重指数(BMI)、糖尿病发病率、空腹血糖、AGEs、AGEs可溶性受体以及2,2-二苯基-1-苦基肼(DPPH)清除率、血清超敏C反应蛋白(hsCRP)、纤溶酶原激活物抑制剂-1(PAI-1)和胎球蛋白-A。在建立血液透析通路时获取的桡动脉片段用茜素红染色以检测钙化。通过免疫组织化学鉴定AGEs沉积物并对其相对含量进行定量。

结果

在简单回归分析中,AGEs的血管含量与BMI、hsCRP、胎球蛋白-A、PAI-1和DPPH清除率呈正相关;在多元回归分析中,只有胎球蛋白-A是独立预测因子。在1级、2级和3级钙化患者中,AGEs免疫染色强度呈显著正相关趋势。无论患者年龄如何,AGEs免疫染色强度均可预测3年心血管死亡率。

结论

本研究表明AGEs参与了CKD患者中膜动脉钙化的发生发展以及动脉AGE沉积对心血管死亡率的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc44/4380091/9275e1c86bc0/DM2015-153978.001.jpg

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