Cellular phenotypes in human stenotic lesions from haemodialysis vascular access

Abstract

Haemodialysis vascular access dysfunction (due to venous stenosis and thrombosis) is a leading cause of hospitalization and morbidity. The aim of the current study was to identify the specific cell types present within stenotic tissue samples from patients with AV fistula and graft failure. Discarded tissue segments were collected from the stenotic portions (usually near the graft-vein anastomosis or the AV anastomosis) of 23 dialysis grafts and 20 AV fistulae, and examined for expression of smooth muscle alpha actin, desmin, vimentin and a macrophage marker. The majority of cells within the venous neointima (both grafts and fistulae) were myofibroblasts, with a smaller number of desmin positive smooth muscle cells. The graft neointima had a similar cellular phenotype, albeit without any desmin positive contractile smooth muscle cells. The majority of cells within the PTFE graft material were macrophages. Analysis of sequential sections revealed the presence of fibroblasts within the venous neointima and intragraft region. Our results demonstrate that contractile smooth muscle cells, myofibroblasts, fibroblasts and macrophages all play a role in the pathogenesis of dialysis access dysfunction (grafts and fistulae). Targeting these specific cell types might result in the development of novel therapeutic paradigms for haemodialysis vascular access dysfunction.