BIOLOGY OF HUMAN MESANGIAL AND VASCULAR ACCESS SHUNT CELLS

动静脉分流/移植物放置在血液透析的前臂 为患者提供血液循环通道。关闭的速度 访问量约为0.8个/年。关闭的原因是 血管壁损伤，伴有组织斑块的形成 细胞外基质(ECM)和管壁细胞。我们已经证明了 低分子硫酸肝素蛋白多糖(HSPG)减少 血管平滑肌细胞周转和细胞外基质沉积。要确定 这些化合物是否具有有益的药理作用 通畅，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明显 减少细胞周转和细胞外基质分泌到培养液中。此外， 这些发现在分离出的人群中也得到了重复 不同的病人来源。因此，现在有计划开发一种 临床方案测试热休克蛋白在预防糖尿病中的疗效 血液透析患者移植物狭窄。如果这项研究的结果 研究是积极的，似乎有理由推测移植物在 其他身体部位，特别是在冠状动脉中，可能是 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.