SMOOTH MUSCLE CELL APOPTOSIS

项目1提出，细胞凋亡在肿瘤的形成过程中起作用。 动脉粥样硬化病变和血管最终狭窄为AS 损伤进展。具体目标侧重于 半胱氨酸蛋白酶和Fas/FasL通路在控制细胞死亡中的作用 血管平滑肌。这包括在动物中使用半胱氨酸天冬氨酸酶抑制剂 死亡被认为起关键作用的模式，以及发展 在决定死亡的共同咽喉点受阻的转基因小鼠的 通过Fas及相关受体介导。这些研究将包括 探讨死亡在控制壁间凝血中的作用， 包括体外和体内两项研究，以探索其可能的作用 纤维蛋白凝胶收缩是血管狭窄的一种机制。最后， 选定的人和小鼠动脉粥样硬化组织将被研究以 根据体外鉴定的分子确定模型的相关性 或者在动物模型中。

Project 1 proposes that apoptosis plays a role in the formation of atherosclerotic lesions and in the ultimate narrowing of the vessel as lesions progress. The Specific Aims focus on the possible role of the cystein proteases and the Fas/FasL pathway in controlling cell death in vascular smooth muscle. This includes use of caspase inhibitors in animal models in which death has been thought to play a key role, and development of a transgenic mouse blocked at a common choke point determining death mediated via Fas and related receptors. These studies will include exploration of the role of death in controlling intramural coagulation, including two studies in vitro and in vivo to explore the possible role of fibrin gel contraction as a mechanism of vascular narrowing. Finally, selected human and mouse atherosclerotic tissues will be studied to determine the relevance of models based on molecules identified in vitro or in animal models.