MCP-1 contributes to arteriovenous fistula failure

Julio P. Juncos, Joseph Peter Grande, Lu Kang, Allan W. Ackerman, Anthony J. Croatt, Zvonimir S Katusic, Karl A Nath

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalJournal of the American Society of Nephrology
Volume22
Issue number1
DOIs
StatePublished - Jan 2011

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Chemokine CCL2
Arteriovenous Fistula
Chemokines
Fistula
Protein Deficiency
Chemokine CCL5
Vascular System Injuries
Transcription Factor AP-1
Smooth Muscle Myocytes
Endothelium
Hyperplasia
Blood Vessels
Renal Dialysis
Rodentia
Patient Care
Leukocytes
Transcription Factors
Up-Regulation
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

MCP-1 contributes to arteriovenous fistula failure. / Juncos, Julio P.; Grande, Joseph Peter; Kang, Lu; Ackerman, Allan W.; Croatt, Anthony J.; Katusic, Zvonimir S; Nath, Karl A.

In: Journal of the American Society of Nephrology, Vol. 22, No. 1, 01.2011, p. 43-48.

Research output: Contribution to journalArticle

Juncos, Julio P. ; Grande, Joseph Peter ; Kang, Lu ; Ackerman, Allan W. ; Croatt, Anthony J. ; Katusic, Zvonimir S ; Nath, Karl A. / MCP-1 contributes to arteriovenous fistula failure. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 1. pp. 43-48.
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