GENE TRANSFER IN MODELS OF ARTERIAL INJURY

我的研究的广泛目标是理解分子 血管平滑肌细胞生长的机制及发展策略 限制损伤后动脉中细胞的增殖 病理生理学。介入治疗的主要局限性 外周或冠状动脉内的手术是血栓形成和 血管内膜形成。我们假设血管内膜细胞的生长和 血栓形成受细胞周期蛋白和血栓前状态的调节 分别为蛋白质。细胞毒性和细胞抑制方法可能会限制 血管损伤后的细胞生长。为了解决这些问题 在假设的基础上，我们提出了三个具体目标：(1)优化非病毒 载体以提高血管细胞中的基因表达，(2)检测 损伤猪血管平滑肌细胞生长的病理生理学研究 高脂血症兔动脉及其细胞毒作用的研究 限制内膜形成，以及(3)检查血栓形成在 血管损伤后血管内膜形成与因子X的关系 基因和一个编码Xa因子抑制物的基因。

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.