THE PATHOLOGY OF ENDOTHELIAL NEOVASCULIZATION

动脉粥样硬化性血管疾病是发病率和 美国内皮细胞损伤/功能障碍导致的死亡率 至少部分疾病和内皮细胞的启动 (EC)对伤害的反应是决定和调节 由此产生的迁移、增殖、合成和收缩反应 中膜平滑肌细胞与血管生成反应 外膜微血管构筑。EC对损伤的反应，受 基础细胞外基质的组成和组织以及 内皮细胞-细胞外基质相互作用，尽管不完全 理解，被认为是一个动态的，复杂的，涉及几个 基质结合蛋白的类别。这项提议的长期目标是 阐明整合素和非整合素细胞表面基质的作用 结合蛋白在调控大血管内皮细胞迁移中的作用 微血管内皮细胞的增殖和血管生成 伤害和对可溶性因子的反应。具体地说，组织培养 大血管内皮细胞剥脱损伤修复的动物模型 微血管内皮细胞血管生成将用于 整合素与非整合素作用机制的表征与测定(S) 整合素基质结合蛋白在组织培养中的免疫标记 光、共焦和电子显微镜水平，北方、南方和In 生物合成的原位杂交和差异文库筛选 标记、免疫沉淀和免疫印迹。实验将集中在 围绕各种基质结合域的合成肽的使用 分子、针对基质分子的抗体和基质结合 蛋白质、cRNA和cDNA探针专用于基质分子和基质 结合蛋白在体外大血管内皮细胞迁移和迁移中的作用 在微血管内皮细胞的体外血管生成研究中。 更好地理解这些过程中细胞-基质的相互作用 可能导致改进的合成材料的设计、生产和实施 促进内皮细胞最佳迁移的移植材料和试剂 在治疗干预和可用于调节的药物之后 损伤后和转移扩散过程中的血管生成反应 癌症的威胁。

Atherosclerotic vascular disease is a major cause of morbidity and mortality in the U.S. Endothelial cell injury/dysfunction is responsible for the initiation of at least some of the disease and the endothelial cell (EC) response to injury is a major factor in determining and modulating the resultant migratory, proliferative, synthetic and contractile responses of the medial smooth muscle cells and the angiogenic response of the adventitial microvasculature. The EC response to injury, modulated by the composition and organization of the underlying extracellular matrix and endothelial cell-extracellular matrix interactions, although incompletely understood, is thought to be a dynamic, complex one involving several classes of matrix binding proteins. The long-term goal of this proposal is to elucidate the roles of integrin and non-integrin cell surface matrix binding proteins in modulating large vessel endothelial cell migration and proliferation and microvascular endothelial cell angiogenesis following injury and in response to soluble factors. Specifically, tissue culture and animal models of large vessel endothelial cell denudation injury-repair and microvascular endothelial cell angiogenesis will be used to characterize and determine the mechanism(s) of action of integrin and non- integrin matrix binding proteins during tissue culture, immunolabeling at light, confocal and electron microscopic levels, Northern, Southern and in situ hybridization and differential library screening, biosynthetic labeling, immunoprecipitation and immunoblotting. Experiments will center around the use of synthetic peptides of various binding domains of matrix molecules, antibodies raised against matrix molecules and matrix binding proteins and cRNA and cDNA probes specific for matrix molecules and matrix binding proteins in vitro large vessel endothelial cell migrations and during in vitro angiogenesis studies with microvascular endothelial cells. A better understanding of cell-matrix interactions during these processes may lead to the design, production and implementation of improved synthetic grafting materials, agents that promote optimal endothelial cell migration following therapeutic intervention and agents that can be used to modulate the angiogenic response following injury and during the metastatic spread of cancer.