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MAINTENANCE AND REPAIR OF VASCULAR ENDOTHELIUM

血管内皮的维护和修复

基本信息

批准号：
3336079
负责人：
DENIS J GOSPODAROWICZ
金额：
$ 19.35万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-12-01 至 1992-06-30
项目状态：
已结题

项目摘要

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.

主要目的是研究生理功能新发现的血管内皮细胞有丝分裂原（VEGF）。我们将分析已知调节 FGF 生物活性的药物是否也作用于血管内皮生长因子水平。这些药物是一个多元化的群体，包括生长因子例如 TGFbeta 或 TNFalpha，以及不相关的分子，例如肝素、苏拉明和鱼精蛋白，已知会影响血管生成过程血管内皮细胞增殖。 VEGF的控制能力将确定与血管生成过程相关的事件。这包括其对血管内皮细胞趋化活性的影响它刺激纤溶酶原激活剂和胶原酶的能力，同时抑制纤溶酶原抑制剂活性。我们将研究表达正常细胞类型与肿瘤细胞类型中的 VEGF。各种正常细胞类型观察血管内皮和平滑肌中 VEGF 的表达情况细胞、血小板、单核细胞、巨噬细胞和颗粒细胞。这些选择细胞类型是因为它们与血管生成过程。如果表达，VEGF 可以在控制中发挥作用发育过程（血管生成、血管生成）以及病理性的一种（动脉粥样硬化）。在肿瘤细胞类型中分析的将是来自血管系统以及神经胶质瘤的细胞细胞。研究不受调节的 VEGF 和 betaFGF 表达对发育过程中，鸡胚胎会感染禽类病毒携带 VEGF 和 betaFGF 基因的逆转录病毒。组织特异性模式然后将追踪表达 VEGF 和 betaFGF 基因的病毒时间的函数。这将与发育异常相关，特别是在血管系统中。我们将定义细胞表面 VEGF 受体。这是克隆受体的第一步，以及了解该分子机制的一步细胞对这种生长因子的反应。