MCP-1 contributes to arteriovenous fistula failure.
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-κB 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.
Mayo Clinic, Guggenheim 542, 200 First Street, SW, Rochester, MN 55905, USA.
Julio P
JP
Juncos
Joseph P
JP
Grande
Lu
L
Kang
Allan W
AW
Ackerman
Anthony J
AJ
Croatt
Zvonimir S
ZS
Katusic
Karl A
KA
Nath
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis / Q000379:methods; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
C491768:Ccl2 protein, mouse; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016328:NF-kappa B; D018808:Transcription Factor AP-1