GENE TRANSFER IN MODELS OF ARTERIAL INJURY

我研究的主要目标是了解 平滑肌细胞生长的机制，并制定战略， 限制损伤后动脉中的细胞增殖 病理生理学 介入治疗的主要局限性 外周动脉或冠状动脉内的手术是血栓形成， 内膜形成 我们假设内膜细胞生长和 血栓形成受细胞周期蛋白和促血栓形成蛋白的调节， 蛋白质，分别。 细胞毒性和细胞抑制方法可能限制 血管损伤后的细胞生长。 为了解决这些 假设，我们提出了三个具体目标：（1）优化非病毒 载体，以改善血管细胞中的基因表达，（2）检查 损伤猪平滑肌细胞生长的病理生理学， 高脂血症兔动脉，并开发细胞毒性方法， 限制内膜形成，和（3）检查血栓形成在 通过研究因子X观察血管损伤后内膜形成 基因和编码因子Xa抑制剂的基因。

The broad objective of my research is to understand the molecular mechanisms of smooth muscle cell growth and to develop strategies to limit cell proliferation in arteries after injury based upon pathophysiology. The major limitations to therapeutic interventional procedures within peripheral or coronary arteries are thrombosis and intimal formation. We hypothesize that intimal cell growth and thrombosis are regulated by cell cycle proteins and prothrombotic proteins, respectively. Cytotoxic and cytostatic approaches may limit cell growth following vascular injury. In order to address these hypotheses, we propose three specific aims: (1) to optimize nonviral vectors to improve gene expression in vascular cells, (2) to examine the pathophysiology of smooth muscle cell growth in injured porcine and hyperlipidemic rabbit arteries and to develop cytotoxic approaches to limit intimal formation, and (3) to examine the role of thrombosis in intimal formation following vascular injury by investigating a factor X gene and a gene that encodes a factor Xa inhibitor.