MCP-1 Contributes to Arteriovenous Fistula Failure
MCP-1 Contributes to Arteriovenous Fistula Failure
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DOI：
10.1681/asn.2010040373
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发表时间：
2011-01-01
影响因子：
13.6
通讯作者：
Nath, Karl A.
中科院分区：
文献类型：
--
作者：
Juncos, Julio P.;Grande, Joseph P.;Nath, Karl A.
血管通路功能障碍影响慢性血液透析患者的护理。阐明这种功能障碍的机制和设计可能中断新生内膜增生和相关发病途径的策略是必要的。在这里，我们发现，在静脉段的小鼠模型的动静脉瘘，单核细胞趋化蛋白-1（MCP-1）的mRNA和蛋白质的增加，伴随着增加的转录因子NF-κ B B和AP-1的活性。MCP-1的遗传缺陷在该小鼠模型中被证明具有显著的保护作用，反映在其形成后6周瘘通畅性增加、静脉壁厚度降低和管腔面积增加。MCP-1缺乏的早期效应是在该模型中发生的CCL 5（RANTES）的显著诱导的减弱，该趋化因子最近被认为是血管损伤的关键参与者。最后，在大鼠动静脉瘘模型中，我们将MCP-1的表达定位于内皮细胞、增殖的平滑肌细胞和浸润的白细胞。总之，MCP-1的显著上调发生在啮齿动物动静脉瘘的静脉段，这种血管病变趋化因子导致瘘的失败。
Vascular access dysfunction compromises the care of patients on chronic hemodialysis. Elucidating the mechanisms of such dysfunction and devising strategies that may interrupt neointimal hyperplasia and relevant pathogenetic pathways are essential. Here, we show that, in the venous segment of a murine model of an arteriovenous fistula, monocyte chemoattractant protein-1 (MCP-1) mRNA and protein increase, accompanied by increased activity of the transcription factors NF-kappa B and AP-1. Genetic deficiency of MCP-1 proved markedly protective in this murine model, reflected by increased fistula patency 6 weeks after its formation, decreased venous wall thickness, and increased luminal area. An early effect of MCP-1 deficiency was the attenuation of the marked induction of CCL5 (RANTES) that occurred in this model, a chemokine recently recognized as a critical participant in vascular injury. Finally, in a rat model of an arteriovenous fistula, we localized expression of MCP-1 to the endothelium, proliferating smooth muscle cells and infiltrating leukocytes. In summary, marked upregulation of MCP-1 occurs in the venous segment of an arteriovenous fistula in rodents, and this vasculopathic chemokine contributes to failure of the fistula.