MAINTENANCE AND REPAIR OF VASCULAR ENDOTHELIUM

本研究的主要目的是研究人体的生理功能。 新发现的血管内皮细胞有丝分裂原(VEGF)。我们将分析 已知的调节成纤维细胞生长因子生物活性的药物是否也作用于 血管内皮生长因子水平。这些药物是一个多样化的群体，包括生长因子。 如转化生长因子β或肿瘤坏死因子α，以及无关分子，如 肝素、苏拉明和鱼精蛋白，已知影响血管生成过程和 血管内皮细胞增殖。血管内皮细胞生长因子的调控能力 将确定与血管生成过程相关的事件。这包括 银杏叶提取物对血管内皮细胞趋化活性的影响 其刺激纤溶酶原激活物和胶原酶的能力，而 抑制纤溶酶原抑制物活性。我们将研究如何表达 血管内皮生长因子在正常和肿瘤细胞类型中的表达。不同的正常细胞类型 血管内皮细胞和血管平滑肌中血管内皮生长因子的表达 细胞、血小板、单核细胞、巨噬细胞和颗粒细胞。这些 选择单元格类型是因为它们与 血管生成过程。如果表达，血管内皮细胞生长因子可能在控制 发育过程(血管生成、血管生成)以及 病理性一(动脉粥样硬化)。在即将出现的肿瘤细胞类型中 分析的对象包括来自血管系统的肿瘤，以及神经胶质瘤。 细胞。未调控的血管内皮生长因子和β-成纤维细胞生长因子表达对血管内皮细胞生长的影响 在发育过程中，雏鸡胚胎会感染禽类 携带血管内皮生长因子和β-成纤维细胞生长因子基因的逆转录病毒。组织特异性图案 表达血管内皮生长因子和β-成纤维细胞生长因子基因的病毒将被作为 时间的作用。这将与发展的异常相关， 尤其是在血管系统中。我们将定义细胞表面 血管内皮生长因子受体。这是克隆受体的第一步， 也是朝着理解人类免疫缺陷的分子机制迈出的一步 细胞对这种生长因子的反应。

The primary objective is to investigate the physiological function of a newly identified vascular endothelial cell mitogen (VEGF). We will analyze whether agents known to modulate the bioactivity of FGF also act at the VEGF level. These agents are a diverse group, including growth factors such as TGFbeta or TNFalpha, as well as unrelated molecules, such as heparin, suramin, and protamine, known to affect the angiogenic process and vascular endothelial cells proliferation. The ability of VEGF to control events related to the angiogenic process will be determined. This includes its effect on the chemotactic activity of vascular endothelial cells and its ability to stimulate plasminogen activator and collagenase, while repressing plasminogen inhibitor activity. We will study the expression of VEGF in normal versus tumor cell types. The various normal cell types to be looked at for VEGF expression are vascular endothelial and smooth muscle cells, platelet, monocytic cells, macrophages, and granulosa cells. These cell types are chosen because of their particular relevance to the angiogenic process. If expressed, VEGF could play a role in controlling developmental processes (angiogenesis, vasculogenesis), as well as a pathological one (atherosclerosis). Among the tumor cell types to be analyzed will be those derived from the vascular systems, as well as glioma cells. To study the effect of unregulated VEGF and betaFGF expression on developmental processes, chick embryos will be infected with avian retrovirus carrying the VEGF and betaFGF gene. The tissue specific pattern of viruses expressing the VEGF and betaFGF gene will then be followed as a function of time. This will be correlated with abnormality of development, particularly in the vascular system. We will define the cell surface receptor for VEGF. This is the first step toward cloning of the receptor, as well as a step towards understanding the molecular mechanism of the cells response to this growth factor.