[Molecular biology of protein C-thrombomodulin pathway. Structure and function, and basic studies on its clinical...

Vascular endothelial cells have several mechanisms which play an active role in preventing blood clot formation in vivo. One of the mechanisms by which prevention is achieved involves a cell surface thrombin receptor, thrombomodulin, which converts thrombin from a procoagulant into an anticoagulant due to accelerating thrombin-catalyzed activation of an anticoagulant protease zymogen, protein C. Activated protein C then proteolytically inactivates coagulation cofactors, Factors Va and VIIIa, in concert with another anticoagulant protein S. Activated protein C is finally neutralized by protein C inhibitor. The physiological relevance of the anticoagulant protein C-thrombomodulin pathway is demonstrated by the identification of hereditary deficiency of protein C or protein S with severe thrombotic complications. The recombinant protein C or thrombomodulin would be useful for treatment of the thrombotic diseases.