ENDOTHELIAL CELL APOPTOSIS

内皮细胞存活和死亡的调节对于 血管发育和体内平衡以及与 动脉硬化，包括血管重塑、动脉粥样硬化和斑块 新生血管形成拟议的研究检查了 内皮细胞的存活和死亡，重点是那些蛋白质， 支持生存还是反对死亡这背后的假设是 建议Bcl-2家族蛋白决定内皮细胞 在基础条件下和暴露于炎性 有毒的刺激。提出的具体目标检验了这一点的几个方面 假设，检查内皮细胞的分子基础和后果， 体外和体内细胞存活和凋亡（程序性细胞死亡） 模型具体目的是：1）表征整合素的作用- 内皮细胞依赖性粘附和信号转导机制 体外存活; 2）表征信号转导途径 由TNF-α介导，诱导Bcl-2同源物A1，A1 抑制; 3）通过产生A1- 缺陷小鼠;和4）检查凋亡的机制， 内皮细胞成为白细胞的前粘附细胞。从以下方面获得的见解： 这些研究可能为治疗 动脉粥样硬化及其并发症。

The regulation of endothelial cell survival and death is critical to vascular development and homeostatis and to processes associated with arteriosclerosis including vascular remodeling, atherogenesis, and plaque neovascularization. The proposed studies examine the molecular basis of endothelial cell survival and death, focusing on those proteins that support survival or oppose death. The underlying hypothesis of this proposal is that proteins of the Bcl-2 family determine endothelial cell survival under both basal conditions and during exposure to inflammatory and toxic stimuli. The specific aims proposed test several aspects of this hypothesis, examining the molecular basis and consequences of endothelial cell survival and apoptosis (programmed cell death) in vitro and in vivo models. The Specific Aims are: 1) to characterize the role of integrin- dependent adherence and signaling in the mechanisms of endothelial cell survival in vitro; 2) to characterize the signal transduction pathways mediated by TNF-alpha that induce the Bcl-2 homologue, A1 and that A1 inhibits; 3) to study the function of A1 in vivo by generating A1- deficient mice; and 4) to examine the mechanisms by which apoptotic endothelial cells become proadhesive for leukocytes. Insights gained from these studies may suggest new potential targets for the treatment of atherosclerosis and its complications.