THE PHYSIOLOGY OF HUMAN PROTEIN C

蛋白C是一种维生素K依赖性血浆蛋白。 蛋白质钙 酶活性形式，是一种有效的抗凝血剂， 凝血级联中因子V和VIII的水平。 蛋白质钙 至少部分地通过提高血凝块溶解的速率来加速血凝块溶解的速率 循环纤溶酶原激活物水平。 由于这些独特的 我们希望确定蛋白质C在人类中的重要性 血栓性疾病 为了实现这一长期目标，我们建议 开发蛋白质和定量功能的筛选试验 蛋白质的分析。 我们将开发一种血浆功能测定法， 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，这似乎是必要的表达抗凝剂 蛋白质Ca的性质 使用这些分析，我们将研究 这些蛋白质的水平发生改变的条件：1）我们有 先前证明，在狗中低水平的凝血酶输注导致 蛋白C的激活。 我们将确定蛋白C的激活 发生在人类普通外科手术的组织创伤、挤压 损伤或在血管内凝血期间与播散性 血管内凝血 在手术患者中，我们将确定 蛋白C激活保护患者术后静脉 血栓形成 2)常用的口服抗凝剂华法林降低 蛋白C水平，我们将确定恢复的关系， 蛋白C和蛋白S与凝血因子VII、IX和X相比， 停止治疗。 3)使用犬模型，我们将确定 蛋白C补充剂将保护动物免受 组织持续输注引起的血管内凝血 凝血活酶。 这些人类和动物研究将成为 人类蛋白C和蛋白S水平诱导变化的重要性 血栓性疾病

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.