Pentosan polysulfate decreases proliferation and extracellular matrix deposition by vascular smooth muscle cells isolated from failed hemodialysis access grafts

(B)ackground: Vascular access failure is a major cause of morbidity, and in creased costs in patients undergoing maintenance hemodialysis. Stenosis, th e most common underlying cause of loss of patency in failed grafts, appears to be caused by an obstructing mass of tissue containing proliferating smo oth muscle cells and their associated extracellular matrix. Methods: To det ermine whether this process was amenable to pharmacologic intervention and/ or prevention, we obtained samples of the material occluding vascular acces ses from 7 patients undergoing revision surgery in order to characterize th e cells contributing to the stenosis. In all 7 patients the outgrowth conta ined predominantly smooth muscle-like cells admired with fibroblasts, which produced a large amount of type IV and type I collagen. Results: Treatment with pentosan polysulfate inhibited cell proliferation and significantly r educed the accumulation of types I and type IV collagens. This was associat ed with increase in metalloproteinase-9 (MMP-9) and a shift of tissue inhib itor of metalloproteinase-3 (TIMP-3) from the cell layer into the medium. C onclusion: These data suggest that pentosan polysulfate (PPS) may have a fa vorable effect in patients with a polytetrafluoroethylene (PFTE) graft by d ecreasing cell proliferation and collagen deposition.