CELLULAR MECHANISMS OF VASCULAR GRAFT FAILURE

血管移植失败的细胞机制

• 批准号: 3352254
• 负责人: ALLAN D. CALLOW
• 金额: $ 20.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352254
• 关键词: artery stenosis; baboons; biomaterial interface interaction; biomaterials; blood vessel prosthesis; cell adhesion; fibroblasts; fluorocarbon polymers; growth factor; human tissue; interleukin 1; monocyte; nucleic acid probes; platelet aggregation; radiotracer; scanning electron microscopy; tissue /cell culture; vascular endothelium; vascular smooth muscle

The clinical utility of small caliber prosthetic arterial grafts is most often limited by stenosis due to intimal hyperplasia. Although it is now widely appreciated that this lesion results from abnormal proliferation of cells, the signals that initiate this hyperplastic response are largely unknown. Previous research has often focused on the platelet, activated by interaction with biomaterials or by altered hemodynamics, as the source of proliferative stimuli. However, it is now apparent that monocytes and endothelial cells can also produce mitogens that stimulate the proliferation of smooth muscle cells and fibroblasts. The role of these two cell types in the hyperplastic response to vascular grafts has heretofore recieved little attention. Accordingly, our initial Specific Aims will focus on the interactions of prosthetic materials with human monocytes or vascular endothelium in relation to the hyperplastic response. SPECIFIC AIM 1: WE WILL TEST THE HYPOTHESIS THAT WELL CHARACTERIZED BIOMATERIALS SUCH AS DACRON, AND EXPANDED POLYTETRAFLUOROETHYLENE (ePTFE), AND NHLBI REFERENCE STANDARDS STIMULATE THE PRODUCTION BY HUMAN MONONUCLEAR PHAGOCYTES OF GROWTH FACTORS AND/OR INFLAMMATORY MEDIATORS SUCH AS INTERLEUKIN-1. SPECIFIC AIM 2: WE WILL TEST THE HYPOTHESIS THAT MONOCYTES ADHERE TO CLINICALLY USED CARDIOVASCULAR BIOMATERIALS SUCH AS DACRON OR (ePTFE) IN VITRO AND TO GRAFT MATERIALS IMPLANTED CHRONICALLY IN BABOONS AFTER THEY DEVELOP A CELLULAR LINING. SPECIFIC AIM 3: WE WILL TEST THE HYPOTHESIS THAT EXPOSURE TO BIOMATERIALS SUCH AS ePTFE OR DACRON STIMULATES PRODUCTION BY HUMAN ENDOTHELIAL OF ACTIVITY THAT PROMOTES THE GROWTH OF SMOOTH MUSCLE CELLS AND/OR FIBROBLASTS. THIS ENDOTHELIAL FUNCTION, ALREADY KNOWN TO BE INDUCED BY CERTAIN INJURIOUS STIMULI, MIGHT CONTRIBUTE TO FAILURE EVEN IF GRAFTS ARE SUCCESSFULLY SEEDED WITH ENDOTHELIUM.

小口径假肢移植物的临床实用性最多 通常由于内膜增生而受到狭窄的限制。 虽然现在是 广泛理解这种病变是由于异常的增殖而引起的 细胞，启动这种增生响应的信号在很大程度上是 未知。 先前的研究通常集中在血小板上，被激活 与生物材料的相互作用或通过改变血流动力学的相互作用，作为来源 增生性刺激。 但是，现在很明显单核细胞和 内皮细胞也可以产生刺激的有丝分裂剂 平滑肌细胞和成纤维细胞的增殖。 这些的作用 对血管移植的增生反应中的两种细胞类型具有 迄今为止，几乎没有得到关注。 因此，我们最初的具体 目的将重点放在假肢与人类的相互作用上 与增生反应有关的单核细胞或血管内皮。 特定目的1：我们将检验以下特征的假设 生物材料，例如DACRON和扩展的聚氟乙烯（EPTFE）， 和NHLBI参考标准刺激人类单核的产生 吞噬生长因子和/或炎症介质（例如） 白介素-1。 特定目的2：我们将测试单核细胞粘附的假设 临床使用的心血管生物材料，例如DACRON或（EPTFE） 体外和移植物材料在狒狒之后长期植入 发展一个细胞衬里。 特定目的3：我们将测试暴露于生物材料的假设 例如EPTFE或DACRON刺激人类内皮的生产 促进平滑肌细胞和/或 成纤维细胞。 这种内皮功能，已知已被诱导 某些有害刺激，即使移植物是 成功地用内皮播种。