C-kit signaling determines neointimal hyperplasia in arteriovenous fistulae.

C-KIT SIGNALING DETERMINES NEOINTIMAL HYPERPLASIA IN ARTERIOVENOUS FISTULAE. Am J Physiol Renal Physiol. 2014 Sep 3; Authors: Skartsis N, Martinez L, Camilo Duque J, Tabbara M, Velazquez OC, Asif A, Andreopoulos F, Salman LH, Vazquez-Padron RI 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 evaluate the role of the receptor tyrosine kinase (RTK) c-Kit in A-V fistula neointima formation. Initially, c-Kit was found in the neointima and adventitia of human brachiobasilic fistulae, while barely detectable in control veins harvested at the time of access creation. Using the rat A-V fistula model to study venous vascular remodeling after fistula creation, we then 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 blocking of c-Kit with imatinib mesylate (Gleevec) and inhibition of stem cell factor (SCF) production with a specific shRNA prevented NIH in the outflow vein of experimental fistulae. In agreement with these data, impaired c-Ki...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research