MAINTENANCE AND REPAIR OF VASCULAR ENDOTHELIUM

血管内皮的维护和修复

• 批准号: 3336074
• 负责人: DENIS J GOSPODAROWICZ
• 金额: $ 18.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336074
• 关键词: affinity chromatography; angiogenesis; antibody formation; antiserum; atherosclerosis; avian leukosis virus; cell growth regulation; cell type; chick embryo; clone cells; collagenase; early embryonic stage; electron microscopy; embryogenesis; enzyme linked immunosorbent assay; fibroblast growth factor; fluorescence microscopy; gel electrophoresis; gene expression; glioma; granulosa cell; growth factor receptors; heparan sulfate; laboratory rabbit; macrophage; mitogens; molecular cloning; monoclonal antibody; plasminogen activator; platelets; protamines; radioimmunoassay; suramin; tissue /cell culture; transforming growth factors; vascular endothelium; vascular smooth muscle

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.

主要目的是研究一个人的生理功能， 新发现的血管内皮细胞有丝分裂原（VEGF）。 我们将分析 已知调节FGF生物活性的试剂是否也在 VEGF水平。 这些代理商是一个多样化的群体，包括生长因子 如TGF β或TNF 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， 血管内皮细胞增殖。 VEGF控制 将确定与血管生成过程相关的事件。 这包括 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， 抑制纤溶酶原抑制剂活性。 我们将研究 正常细胞与肿瘤细胞类型中的VEGF。 各种正常细胞类型， 血管内皮细胞和平滑肌中VEGF的表达 细胞、血小板、单核细胞、巨噬细胞和颗粒细胞。 这些 选择细胞类型是因为它们与细胞的特定相关性。 血管生成过程 如果表达，VEGF可能在控制肿瘤生长方面发挥作用。 发育过程（血管生成，血管生成），以及 病理性1（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那些 细胞 为了研究VEGF和betaFGF表达不受调节对 在鸡胚发育过程中， 携带VEGF和betaFGF基因的逆转录病毒。组织特异性模式 表达VEGF和betaFGF基因的病毒将作为一种 时间的功能。 这与发育异常有关， 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， 同时也是理解这一疾病的分子机制的一步。 细胞对这种生长因子的反应。