REGULATION OF KININ DELIVERY ON HUVEC

HUVEC 上激肽传递的调节

• 批准号: 6745141
• 负责人: ALVIN H SCHMAIER
• 金额: $ 32.77万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6745141
• 关键词: gene targeting; genetically modified animals; human tissue; kallikreins; kininogens; kinins; laboratory mouse; membrane proteins; molecular weight; plasminogen activator; protein purification; protein transport; receptor binding; receptor expression; thrombosis; vascular endothelium

DESCRIPTION (Applicant's abstract): The hypothesis that forms the basis of this proposal is that the assembly of high molecular weight kininogen on a multiprotein kininogen receptor results in regulated activation of the enzymes of the plasma kallikrein/kinin system. Activation of the proteins of the plasma kallikrein/kinin system (high molecular weight kininogen, prekallikrein, and factor XII) influences vascular biology by modulating vascular tone and the constitutive antithrombotic nature of the intravascular compartment. Understanding the function of the plasma kallikrein/kinin system is still in its infancy. The fact that deficiencies of these proteins gave abnormal surface-mediated coagulation assays incorrectly oriented earlier investigators to the role of these proteins in intrinsic coagulation. The purpose of these investigations is to develop new understandings of this system's contribution to vascular biology. The specific aims of this proposal are as follows: Specific Aim #1: The endothelial cell plasma prekallikrein activator that initiates activation of the plasma kallikrein/kinin system will be identified and characterized. Specific Aim #2: The interactions of high molecular weight kininogen and factor XII with the urokinase plasminogen activator receptor (uPAR) will be characterized. Specific Aim #3: Animal models for thrombosis will be utilized to ascertain the contributions of bradykinin B2 receptors to the constitutive anticoagulant nature of the intravascular compartment. These investigations will determine physiological activities that define the plasma kallikrein/kinin system. These studies are intended to characterize this system's contribution to vascular biology and to develop new strategies to modulate intravascular thrombosis.

描述（申请人摘要）：构成此基础的假设 建议将高分子量激肽原组装在 多蛋白激肽原受体导致酶的调节性激活 血浆激肽释放酶/激肽系统。激活血浆蛋白 激肽释放酶/激肽系统（高分子量激肽原，前激肽释放酶，和 因子XII）通过调节血管张力和血管紧张度来影响血管生物学。 血管内隔室的组成性抗血栓性质。 了解血浆激肽释放酶/激肽系统的功能仍然是在 它的婴儿期。事实上，这些蛋白质的缺乏会导致异常的 表面介导的凝血试验错误地引导了早期的研究者 这些蛋白质在内源性凝血中的作用。施行本 调查的目的是对该系统的贡献有新的认识 到血管生物学。这项建议的具体目标如下： 具体目标#1：内皮细胞血浆前激肽释放酶激活剂， 将鉴定血浆激肽释放酶/激肽系统的启动激活 和表征了 具体目标#2：高分子量激肽原和因子的相互作用 十二与尿激酶纤溶酶原激活物受体（uPAR）将是 表征了 具体目标#3：将使用血栓形成的动物模型来确定 缓激肽B2受体对组成性抗凝剂的作用 血管内室的性质。 这些研究将确定生理活动， 血浆激肽释放酶/激肽系统这些研究旨在描述这种 系统对血管生物学的贡献，并开发新的策略， 调节血管内血栓形成。