Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula
Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula
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DOI：
10.1016/j.atherosclerosis.2009.08.044
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发表时间：
2010-03-01
期刊：
影响因子：
5.3
通讯作者：
Grandaliano, Giuseppe
中科院分区：
文献类型：
--
作者：
Castellano, Giuseppe;Di Vittorio, Angela;Grandaliano, Giuseppe
目的：五角蛋白-3(PTX3)在血管病理发展中起重要作用。动静脉内瘘(AVF)狭窄导致其失败是血液透析患者并发症的主要原因。到目前为止，对AVF狭窄的发病机制知之甚少。本研究的目的是探讨PTX3在这一环境中的潜在作用。方法和结果：44例终末期肾病患者在动静脉瘘形成时采集了静脉壁样本。有10名患者发生了动静脉瘘狭窄，这些患者在动静脉瘘手术翻修过程中获得了静脉壁的第二部分。激光共聚焦扫描显微镜显示，PTX3免疫染色在失败的AVF中显著增加，显示出与内皮细胞标志物的特异性共定位。AVF修订时分离的循环单个核细胞PTX3mRNA的表达显著高于AVF创建时采集的循环单个核细胞。值得注意的是，在AVF狭窄的血管内皮细胞上可观察到与PTX3共定位的C5b-9沉积。结论：本研究首次在AVF失败的血管内皮细胞水平上证实了PTX3的沉积与补体激活密切相关，提示PTX3在AVF狭窄的发病机制中具有调节先天免疫的作用。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: Pentraxin-3 (PTX3) has been suggested to play a role in the development of vascular pathology. Stenosis of arteriovenous fistula (AVF) leading to its failure is the major cause of morbidity in hemodialysis patients. To date, little is known on the pathogenesis of AVF stenosis. The aim of the present study was to investigate the potential role of PTX3 in this setting.Methods and results: A sample of venous wall was collected at the time of AVF formation in 44 patients with end stage renal disease. Ten patients developed AVF stenosis and from these patients a second portion of the venous wall was obtained during surgical revision of the AVF. Confocal laser scanning microscopy demonstrated that PTX3 immunostaining, hardly detectable in native AVF, was significantly increased in failed AVF, showing a specific co-localization with endothelial cell markers. Circulating mononuclear cells isolated at the time of AVF revision presented a significantly higher PTX3 mRNA expression than those collected during AVF creation. Interestingly, a significant deposition of C5b-9 on endothelial cells, co-localizing with PTX3, was observed in stenotic AVF.Conclusion: The present study demonstrates for the first time a close association between PTX3 deposition and complement activation at the endothelial cell level in failed AVF and suggests a role for PTX3 in modulating innate immunity in the pathogenesis of AVF stenosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.