Arteriovenous shunts/grafts are placed in the forearm of hemodialysis patients to provide access to the circulation. The rate of closure of access sites is approximately 0.8/year. The cause of closure is vascular wall injury with the formation of plaques of tissue containing extracellular matrix (ECM) and vessel wall cells. We have shown that low molecular weight heparin sulfate proteoglycans (HSPG) decreases vascular smooth muscle cell turnover and ECM deposition. To determine whether these compounds might have a beneficial pharmacologic action on access patency, we isolated cells from materials removed from stenotic grafts/shunts at the time of revision. We find that HSPG markedly decrease cell turnover and ECM secretion into the medium. Furthermore, these findings were replicated in populations isolated from a number of different patient sources. Thus, there are now plans to develop a clinical protocol to test the efficacy of HSPG in the prevention of graft stenosis in hemodialysis patients. If the findings from this study are positive, it seems reasonable to speculate that grafts in other body sites, specifically in the coronary arteries, might be therapeutic targets for HSPG.
