Weiler H, Kerschen E
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin 534226, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:127-31. doi: 10.1111/j.1538-7836.2009.03377.x.
Activated protein C (aPC) is the key effector protease of the natural protein C anticoagulant pathway and exerts anticoagulant, as well as anti-inflammatory activity. This dual mode of action has been thought to underlie the therapeutic efficacy of recombinant aPC in the treatment of patients suffering from severe forms of sepsis. The development and characterization of recombinant variants of aPC with altered bioactivity profiles has generated an opportunity to test this concept by dissecting the roles of aPC's anticoagulant and cell-signaling functions in the treatment of sepsis. Animal studies suggest that aPC variants with near-normal signaling function, but with greatly diminished anticoagulant potential may exhibit a substantially improved risk-to-benefit ratio in sepsis therapy.
活化蛋白C（aPC）是天然蛋白C抗凝途径的关键效应蛋白酶，具有抗凝和抗炎活性。这种双重作用模式被认为是重组aPC治疗严重脓毒症患者疗效的基础。具有改变的生物活性谱的aPC重组变体的开发和特性分析，为通过剖析aPC的抗凝和细胞信号传导功能在脓毒症治疗中的作用来验证这一概念提供了机会。动物研究表明，信号传导功能接近正常但抗凝潜力大大降低的aPC变体，在脓毒症治疗中可能表现出显著改善的风险效益比。
