Gierula Magdalena, Ahnström Josefin
Centre for Haematology, Imperial College London, London, UK.
J Thromb Haemost. 2020 Nov;18(11):2801-2811. doi: 10.1111/jth.15025. Epub 2020 Aug 24.
Protein S is a critical regulator of coagulation that functions as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. It also has direct anticoagulant functions, inhibiting the intrinsic tenase and prothrombinase complexes. Through these functions, protein S regulates coagulation during both its initiation and its propagation phases. The importance of protein S in hemostatic regulation is apparent from the strong association between protein S deficiencies and increased risk for venous thrombosis. This is most likely because both APC and TFPIα are inefficient anticoagulants in the absence of any cofactors. The detailed molecular mechanisms involved in protein S cofactor functions remain to be fully clarified. However, recent advances in the field have greatly improved our understanding of these functions. Evidence suggests that protein S anticoagulant properties often depend on the presence of synergistic cofactors and the formation of multicomponent complexes on negatively charged phospholipid surfaces. Their high affinity binding to negatively charged phospholipids helps bring the anticoagulant proteins to the membranes, resulting in efficient and targeted regulation of coagulation. In this review, we provide an update on protein S and how it functions as a critical hemostatic regulator.
蛋白S是凝血的关键调节因子，作为活化蛋白C（APC）和组织因子途径抑制物（TFPI）途径的辅因子发挥作用。它还具有直接抗凝功能，可抑制内源性凝血酶原酶复合物和凝血酶原酶复合物。通过这些功能，蛋白S在凝血的起始和传播阶段均发挥调节作用。蛋白S缺乏与静脉血栓形成风险增加之间的密切关联表明了其在止血调节中的重要性。这很可能是因为在没有任何辅因子的情况下，APC和TFPIα都是低效的抗凝剂。蛋白S辅因子功能所涉及的详细分子机制仍有待充分阐明。然而，该领域的最新进展极大地增进了我们对这些功能的理解。有证据表明，蛋白S的抗凝特性通常取决于协同辅因子的存在以及在带负电荷的磷脂表面形成多组分复合物。它们与带负电荷的磷脂的高亲和力结合有助于将抗凝蛋白带到膜上，从而实现对凝血的有效且有针对性的调节。在本综述中，我们提供了关于蛋白S及其作为关键止血调节因子如何发挥作用的最新信息。
