Protein C anticoagulant activity in relation to anti-inflammatory and anti-apoptotic activities.
The anticoagulant protein C system is a dual function cofactor-dependent system. On one hand, it is designed to regulate coagulation, maintain the fluidity of the vasculature and prevent thrombosis. On the other hand, the protein C pathway provides anti-inflammatory and cytoprotective activities. Protein C, a vitamin K-dependent serine protease zymogen that circulates in plasma, is converted by limited proteolysis to activated protein C (APC) by the thrombin-thrombomodulin-endothelial protein C receptor complex on endothelial surfaces. APC and the cofactors of the protein C pathway exert two major distinct types of activities, namely a well-studied anticoagulant activity and a more recently revealed cytoprotective activity due to direct effects on cells. Because of these pleiotropic properties, APC and the protein C pathway components have important roles in the body's host-defense system and provide opportunities for therapeutic treatment of complex and challenging medical disorders, including thrombosis, severe sepsis and stroke.
Mosnier
Laurent O
LO
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Griffin
John H
JH
D000925:Anticoagulants / Q000378:metabolism* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001777:Blood Coagulation / Q000502:physiology*; D006207:Half-Life; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007249:Inflammation; D016377:Organ Transplantation; D011486:Protein C / Q000378:metabolism* / Q000627:therapeutic use; D012307:Risk Factors; D018805:Sepsis / Q000188:drug therapy; D020521:Stroke / Q000188:drug therapy
D000925:Anticoagulants; D011486:Protein C