c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Nikolaos Skartsis, Laisel Martinez, Juan Camilo Duque, Marwan Tabbara, Omaida C. Velazquez, Arif Asif, Fotios Andreopoulos, Loay H. Salman, Roberto I. Vazquez-Padron

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Stenosis of arteriovenous (A-V) fistulae secondary to neointimal hyperplasia (NIH) compromises dialysis delivery, which worsens patients’ quality of life and increases medical costs associated with the maintenance of vascular accesses. In the present study, we evaluated the role of the receptor tyrosine kinase c-Kit in A-V fistula neointima formation. Initially, c-Kit was found in the neointima and adventitia of human brachiobasilic fistulae, whereas it was barely detectable in control veins harvested at the time of access creation. Using the rat A-V fistula model to study venous vascular remodeling, we analyzed the spatial and temporal pattern of c-Kit expression in the fistula wall. Interestingly, c-Kit immunoreactivity increased with time after anastomosis, which concurred with the accumulation of cells in the venous intima. In addition, c-Kit expression in A-V fistulae was positively altered by chronic kidney failure conditions. Both blockade of c-Kit with imatinib mesylate (Gleevec) and inhibition of stem cell factor production with a specific short hairpin RNA prevented NIH in the outflow vein of experimental fistulae. In agreement with these data, impaired c-Kit activity compromised the development of NIH in A-V fistulae created in c-KitW/Wv mutant mice. These results suggest that targeting of the c-Kit signaling pathway may be an effective approach to prevent postoperative NIH in A-V fistulae.

Original languageEnglish (US)
Pages (from-to)F1095-F1104
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number9
DOIs
StatePublished - Nov 1 2014

Keywords

  • Arteriovenous fistula
  • Hemodialysis
  • Neointima

ASJC Scopus subject areas

  • Physiology
  • Urology

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