MECHANISMS OF ARTERIAL GRAFT HEALING

动脉移植物愈合机制

• 批准号: 6116376
• 负责人: ALEXANDER W CLOWES
• 金额: $ 8.67万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116376
• 关键词: Mammalia; Primates; animal tissue; biomaterials; cardiovascular system; prosthesis; surgery

In the past year we continued our studies on how intimal thickening develops in polytetrafluoroethylene (PTFE) arterial grafts and in injured arteries in baboons. We have pursued the hypothesis that nitric oxide (NO) is a major negative regulator of smooth muscle cell (SMC) growth in blood vessels, because high blood flow suppresses intimal thickening and induces the endothelial nitric oxide synthase gene (ecNOS). Our experiments with agents to block ecNOS cause vasoconstriction but do not induce SMC proliferation unless there is some degree of injury. In addition, we have performed experiments with antibodies to platelet-derived growth factor receptor-(-( (PDGF-R-(-() to define a role for PDGF in intimal thickening. PDGFR-( blockade inhibits intimal thickening induced by injury or a switch in blood flow. We have also tried to extend our work to clinical application. We have developed an explant system and have shown that SMC growth in explants resembles very closely SMC growth in injured artery. We now hope to use the explant system to define the properties of human SMCs in saphenous vein explants. The ultimate goal is to provide a link between animal studies and outcome in humans.

去年，我们继续研究聚四氟乙烯 (PTFE) 动脉移植物和狒狒受损动脉的内膜增厚情况。 我们假设一氧化氮 (NO) 是血管中平滑肌细胞 (SMC) 生长的主要负调节因子，因为高血流量会抑制内膜增厚并诱导内皮一氧化氮合酶基因 (ecNOS)。 我们用阻断 ecNOS 的药物进行的实验会导致血管收缩，但不会诱导 SMC 增殖，除非存在一定程度的损伤。 此外，我们还用血小板源性生长因子受体-(-( (PDGF-R-(-()) 抗体进行了实验，以确定 PDGF 在内膜增厚中的作用。PDGFR-( 阻断可抑制由损伤或损伤引起的内膜增厚。我们还尝试将我们的工作扩展到临床应用，我们开发了一种外植体系统，并表明外植体中的 SMC 生长与受损动脉中的 SMC 生长非常相似，我们现在希望使用该外植体。系统来定义隐静脉外植体中人类 SMC 的特性，最终目标是在动物研究和人类结果之间建立联系。