FACTOR VIIa IN COAGULATION/THROMBOSIS

当血浆蛋白酶VIIa因子与细胞表面完整的膜蛋白组织因子结合时，凝血级联反应被触发。由此产生的两个亚基的酶活性因数为IX和X，通过有限的蛋白质分解。该项目的长期目标是了解组织因子/因子VIIa复合体在血栓性疾病中的作用，重点是了解血浆因子VIIa水平和组织因子基因多态性在高凝状态下的作用，以及磷脂成分和抗磷脂抗体如何改变因子VIIa/组织因子的功能。具体地说，该项目将解决以下问题：(1)升高的血浆凝血因子VIIa或凝血因子-抗凝血酶复合体水平是否为血栓性疾病的危险因素？(2)组织因子基因的多态是否与血栓性疾病的风险相关？(3)磷脂-GLA结构域的相互作用如何影响因子VIIa的活性？抗磷脂抗体和脂质氧化如何改变组织因子的活性？实现该项目的目标将提供有关如何调节血液凝结系统触发阶段的基本知识。它还将提供对血浆因子VIIa作为血栓性疾病风险因素的作用的见解。

The clotting cascade is triggered when the plasma protease, factor VIIa, binds to the integral membrane protein, tissue factor, on cell surfaces. The resulting two-subunit enzyme activities factors IX and X by limited proteolysis. The long-term goal of this project is to understand the role of the tissue factor/factor VIIa complex in thrombotic disease, with emphasis on understanding the role of plasma factor VIIa levels and tissue factor gene polymorphisms in hypercoagulable states, and how phospholipid compositions and anti-phospholipid antibodies may alter factor VIIa/tissue factor function. Specifically, the project will address the following questions: (1) Are elevated plasma levels of factor VIIa or factor VIIa-anti-thrombin complexes risk factors for thrombotic disease? (2) Are polymorphisms in the tissue factor gene associated with risk of thrombotic disease? (3) How do phospholipid-Gla domain interactions affect factor VIIa activity? How do anti-phospholipid antibodies and lipid oxidation alter the activity of tissue factor? Achieving the goals of this project will provide basic knowledge about how the triggering phase of the blood clotting system is regulated. It will also provide insights into the role of plasma factor VIIa as a risk factor for thrombotic disease.