BIOLOGY OF HUMAN MESANGIAL AND VASCULAR ACCESS SHUNT CELLS

动静脉分流器/移植物放置在血液透析的前臂 患者提供进入血液循环的通道。 关闭率 访问站点约为0.8/年。 关闭的原因是 血管壁损伤，形成含有 细胞外基质（ECM）和血管壁细胞。 我们已经证明 低分子量硫酸肝素蛋白聚糖（HSPG）减少 血管平滑肌细胞更新和ECM沉积。 以确定 这些化合物是否可能具有有益的药理作用， 为了获得通畅性，我们从狭窄处取出的材料中分离出细胞 翻修时的移植物/分流。 我们发现HSPG显著地 减少细胞周转和ECM分泌到培养基中。 此外，委员会认为， 这些发现在分离自一些 不同的患者来源。 因此，现在有计划开发一个 测试HSPG在预防 血液透析患者的移植物狭窄。 如果这次调查的结果 研究是积极的，似乎有理由推测，移植物在 其他身体部位，特别是冠状动脉， HSPG的治疗靶点

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.