THE PHYSIOLOGY OF HUMAN PROTEIN C

人类蛋白质 C 的生理学

• 批准号: 3341459
• 负责人: PHILIP Cinnamon COMP
• 金额: $ 6.61万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-06-01 至 1986-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341459
• 关键词: anticoagulants; blood coagulation tests; blood proteins; coagulation factor IX; coagulation factor VII; coagulation factor X; disseminated intravascular coagulation; immunohematology; nutrition related tag; protein C; thrombin; thromboplastin; thrombosis; vitamin K; warfarin

Protein C is a vitamin K dependent plasma protein. Protein Ca, the enzymatically active form, is a potent anticoagulant functioning at the levels of factors V and VIII in the clotting cascade. Protein Ca also accelerates the rate of blood clot lysis at least in part by elevating the levels circulating plasminogen activator. Because of these unique properties we wish to determine the importance of protein C in human thrombotic disease. To accomplish this long-term goal we propose to develop both screening assays for the protein and quantitative functional assays for the protein. We will develop a functional assay for plasma levels of protein Ca, and for another vitamin K dependent plasma protein, protein S, which appears essential for expression of the anticoagulant properties of protein Ca. Using these assays we will investigate conditions in which the levels of these proteins are altered: 1) We have previously demonstrated that low-level thrombin infusion in dogs results in the activation of Protein C. We will determine if activation of Protein C occurs in humans following the tissue trauma of general surgery, crush injury or during the intravasclar clotting associated with disseminated intravascular coagulation. In the surgery patients we will determine if protein C activation protects the patients from postoperative venous thrombosis. 2) The commonly used oral anticoagulant warfarin lowers protein C levels and we will determine the relationship of the recovery of protein C and protein S to that of factors VII, IX and X when warfarin therapy is discontinued. 3) Using a canine model we will determine if protein C supplementation will protect animals from disseminated intravascular coagulation induced by the continuous infusion of tissue thromboplastin. These human and animal studies will be an index of the importance of induced changes in protein C and protein S levels in human thrombotic disease.

蛋白C是维生素K依赖性血浆蛋白。 蛋白质Ca， 酶活性形式，是一种有效的抗凝剂 凝血级联的因子V和VIII的水平。 蛋白质CA也是 至少通过提升至少部分地加速了血凝块溶解的速度 水平循环纤溶酶原激活剂。 因为这些独特 我们希望确定蛋白质C在人类中的重要性 血栓性疾病。 为了实现这个长期目标，我们建议 开发蛋白质和定量功能的筛选测定 蛋白质的测定。 我们将开发血浆功能测定法 蛋白Ca的水平，对于另一种维生素K依赖性血浆蛋白的水平， 蛋白质S，这对于抗凝剂的表达至关重要 蛋白质的特性。 使用这些测定我们将调查 这些蛋白质水平改变的条件：1）我们有 以前证明，狗中的低水平凝血酶输注导致 蛋白质C的激活。我们将确定蛋白C的激活是否激活 发生在一般手术的组织创伤之后，发生在人类中 受伤或与传播有关 血管内凝血。 在手术患者中，我们将确定是否 蛋白C激活可保护患者免受术后静脉 血栓形成。 2）常用的口服抗凝华法林降低 蛋白C水平，我们将确定恢复的关系 蛋白C和蛋白质S到WARFARIN时的因素VII，IX和X的蛋白质S 治疗已停止。 3）使用犬类模型，我们将确定是否 补充蛋白C将保护动物免受传播 由组织连续输注诱导的血管内凝血 血栓形成蛋白。 这些人类和动物研究将是 人类蛋白C和蛋白质水平变化的重要性 血栓性疾病。