Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts
Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts
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DOI：
10.1046/j.1523-1755.2001.0590062325.x
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发表时间：
2001-06-01
影响因子：
19.6
通讯作者：
Heffelfinger, SC
中科院分区：
文献类型：
--
作者：
Roy-Chaudhury, P;Kelly, BS;Heffelfinger, SC
背景血管通路功能障碍是美国血液透析人群发病和住院的最重要原因，每年造成的损失达10亿美元。静脉新生内膜增生（VNH）的特点是狭窄和随后的血栓形成占绝大多数的病理导致聚四氟乙烯（PTFE）透析移植失败。尽管问题的严重性和成本的巨大性（10亿美元），目前还没有预防或治疗PTFE透析移植物中静脉新生内膜增生的有效疗法。在手术翻修期间，从狭窄PTFE移植物的移植物-静脉吻合处采集组织样本。采用标准光学显微镜和免疫组化方法对标本进行新生内膜增生的程度和特定细胞类型、细胞因子和基质蛋白的表达进行分级。VNH的特征为（1）存在平滑肌细胞/肌成纤维细胞，（2）细胞外基质成分蓄积，（3）新生内膜和外膜内血管生成，以及（4）存在PTFE移植物材料衬里的活性巨噬细胞层。血小板衍生生长因子（PDGF）、碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）在静脉新生内膜内的平滑肌细胞/肌成纤维细胞、PTFE移植物两侧内衬的巨噬细胞以及新生内膜和外膜内的血管中表达。我们的研究结果表明，巨噬细胞，特异性细胞因子（bFGF，PDGF和VEGF），和血管生成内的新生内膜和外膜可能有助于在PTFE透析移植物的VNH的发病机制。针对这些特定介质和过程的干预措施可能会成功降低血管通路功能障碍的巨大人力和经济成本。
Background. Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of $1 billion per annum. Venous neointimal hyperplasia (VNH) characterized by stenosis and subsequent thrombosis accounts for the overwhelming majority of pathology resulting in polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem and the enormity of the cost ($1 billion), there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts.Methods. Tissue samples were collected from the graft-vein anastomosis of stenotic PTFE grafts during surgical revision. Specimens were graded using standard light microscopy and immunohistochemistry for the magnitude of neointimal hyperplasia and for the expression of specific cell types, cytokines, and matrix proteins.Results. VNH was characterized by the (1) presence of smooth muscle cells/myofibroblasts, (2) accumulation of extracellular matrix components, (3) angiogenesis within the neointima and adventitia, and (4) presence of an active macrophage cell layer lining the PTFE graft material. Platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were expressed by smooth muscle cells/myofibroblasts within the venous neointima, by macrophages lining both sides of the PTFE graft, and by vessels within the neointima and adventitia.Conclusions. Our results suggest that macrophages, specific cytokines (bFGF, PDGF, and VEGF), and angiogenesis within the neointima and adventitia are likely to contribute to the pathogenesis of VNH in PTFE dialysis grafts. Interventions aimed at these specific mediators and processes may be successful in reducing the very significant human and economic costs of vascular access dysfunction.