REGULATION OF KININ DELIVERY ON HUVEC

描述(申请人的摘要)：构成这一基础的假设 建议将高相对分子质量的激肽原组装在 多蛋白激肽原受体导致酶的调节激活 血浆激肽释放酶/激肽系统。激活血浆中的蛋白质 激肽释放酶/激肽释放酶系统(高分子量激肽原、激肽释放酶原和 凝血因子XII)通过调节血管张力而影响血管生物学 血管内间隔的结构性抗血栓性质。 对血浆激肽释放酶/激肽释放酶系统功能的了解仍在 它还处于初级阶段。事实上，这些蛋白质的缺陷导致了异常 表面介导的凝血试验错误地定位了早期的研究人员 这些蛋白质在内源性凝血中的作用。这些活动的目的是 调查是为了对这一系统的贡献有新的理解 血管生物学。这项建议的具体目标如下： 特定目标#1：内皮细胞血浆前激肽释放酶激活剂 启动血浆激肽释放酶/激动素系统的激活将被确定 并以此为特征。 特定目标#2：高分子量激肽原与因子的相互作用 具有尿激酶型纤溶酶原激活物受体(UPAR)的XII将 特色化的。 具体目标#3：将利用血栓形成的动物模型来确定 缓激肽B2受体在成分抗凝剂中的作用 血管内间隔的性质。 这些研究将确定定义 血浆激肽释放酶/激肽系统。这些研究旨在描述这一点 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。

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.