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

Background: Vascular access failure is a major cause of morbidity, and increased costs in patients undergoing maintenance hemodialysis. Stenosis, the most common underlying cause of loss of patency in failed grafts, appears to be caused by an obstructing mass of tissue containing proliferating smooth muscle cells and their associated extracellular matrix. Methods: To determine whether this process was amenable to pharmacologic intervention and/or prevention, we obtained samples of the material occluding vascular accesses from 7 patients undergoing revision surgery in order to characterize the cells contributing to the stenosis. In all 7 patients the outgrowth contained predominantly smooth muscle-like cells admixed with fibroblasts, which produced a large amount of type IV and type I collagen. Results: Treatment with pentosan polysulfate inhibited cell proliferation and significantly reduced the accumulation of types I and type IV collagens. This was associated with increase in metalloproteinase-9 (MMP-9) and a shift of tissue inhibitor of metalloproteinase-3 (TIMP-3) from the cell layer into the medium. Conclusion: These data suggest that pentosan polysulfate (PPS) may have a favorable effect in patients with a polytetrafluoroethylene (PFTE) graft by decreasing cell proliferation and collagen deposition.