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 是一种维生素 K 依赖性血浆蛋白。 蛋白钙， 酶活性形式，是一种有效的抗凝血剂，在 凝血级联中因子 V 和 VIII 的水平。 蛋白质钙也 至少部分通过提高血凝块溶解速度 循环纤溶酶原激活剂水平。 正因为这些独特的 我们希望确定蛋白 C 对人类的重要性的特性 血栓性疾病。 为了实现这一长期目标，我们建议 开发蛋白质筛选分析和定量功能分析 蛋白质测定。 我们将开发血浆功能测定 蛋白质 Ca 水平，以及另一种维生素 K 依赖性血浆蛋白， 蛋白 S，对于抗凝剂的表达至关重要 蛋白质钙的性质 我们将使用这些分析进行研究 这些蛋白质水平发生改变的条件：1）我们有 先前证明，给狗注射低水平的凝血酶会导致 蛋白 C 的激活。我们将确定蛋白 C 的激活是否 发生在人类普通手术、挤压造成的组织创伤之后 损伤或与播散性相关的血管内凝血期间 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的影响 血栓形成。 2）常用口服抗凝药华法林降低 蛋白C水平与我们将确定的恢复的关系 当华法林使用时，蛋白 C 和蛋白 S 与因子 VII、IX 和 X 的关系 治疗停止。 3）使用犬科动物模型，我们将确定是否 补充蛋白 C 将保护动物免受传播 组织持续输注引起血管内凝血 凝血活酶。 这些人类和动物研究将成为 诱导人类蛋白 C 和蛋白 S 水平变化的重要性 血栓性疾病。