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

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.