MECHANISMS OF ARTERIAL GRAFT HEALING

在过去的一年里，我们继续研究聚四氟乙烯（PTFE）动脉移植物和狒狒受伤动脉内膜增厚的发展情况。我们假设一氧化氮（NO）是血管平滑肌细胞（SMC）生长的主要负调节因子，因为高血流量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的药物进行的实验导致血管收缩，但不诱导SMC增殖，除非有一定程度的损伤。此外，我们还对血小板衍生生长因子受体-(-(PDGF- r-(-())的抗体进行了实验，以确定PDGF在内膜增厚中的作用。PDGFR-阻断抑制损伤或血流开关引起的内膜增厚。我们也试图将我们的工作扩展到临床应用。我们已经开发了一个外植体系统，并表明外植体中的SMC生长与损伤动脉中的SMC生长非常相似。我们现在希望使用移植系统来定义人类隐静脉移植的SMCs的特性。最终目标是在动物研究和人类结果之间建立联系。

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.