PATHOLOGY OF ENDOTHELIAL NEOVASCULIZATION

动脉粥样硬化性血管疾病是发病的主要原因， 在美国，内皮细胞损伤/功能障碍是导致 用于引发至少一些疾病和内皮细胞 (EC)对损伤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， 中膜平滑肌细胞和血管生成反应， 外膜微血管 EC对损伤的反应，由 细胞外基质的组成和组织， 内皮细胞-细胞外基质相互作用，虽然不完全 据了解，被认为是一个动态的，复杂的，涉及几个 基质结合蛋白的种类。 该提案的长期目标是 阐明整合素和非整合素细胞表面基质的作用 调节大血管内皮细胞迁移的结合蛋白， 增殖和微血管内皮细胞血管生成 损伤和对可溶性因子的反应。 具体来说，组织培养 大血管内皮细胞剥脱损伤修复动物模型 和微血管内皮细胞血管生成将被用于 表征并确定整合素和非整合素的作用机制， 组织培养过程中的整合素基质结合蛋白，免疫标记， 光学、共聚焦和电子显微镜水平，北方、南方和 原位杂交和差异文库筛选，生物合成 标记、免疫沉淀和免疫印迹。 实验将集中在 围绕使用合成肽的各种结合域的基质， 分子，针对基质分子和基质结合产生的抗体 特异于基质分子和基质的蛋白质和cRNA和cDNA探针 体外大血管内皮细胞迁移和 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的细胞-基质相互作用 可能导致设计，生产和实施改进的合成 移植材料、促进最佳内皮细胞迁移的试剂 在治疗性干预和可用于调节 损伤后和转移扩散期间的血管生成反应 癌症。

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.