title: Activated protein C--an anticoagulant that does more than stop clots.
abstract: Activated protein C (APC) is a glycoprotein derived from its precursor, protein C and formed by the cleavage of an activation peptide by thrombin bound to thrombomodulin. Originally thought to be synthesized exclusively by the liver, recent reports have shown that protein C is synthesized by endothelial cells, keratinocytes and some hematopoietic cells. APC functions as a physiological anticoagulant with cytoprotective, anti-inflammatory and anti-apoptotic properties. In vitro and preclinical data have revealed that APC exerts its protective effects via an intriguing mechanism requiring endothelial protein C receptor and the thrombin receptor, protease-activated receptor-1. Remarkably, even though APC cleaves this receptor in an identical fashion to thrombin, it exerts opposing effects. Recently approved as a therapeutic agent for severe sepsis, APC is now emerging as a potential treatment for a number of autoimmune and inflammatory diseases including lung disorders, spinal cord injury and chronic wounds. The future pharmacologic use of APC holds remarkable promise.
authors.affiliation: Sutton Arthritis Research Laboratories, Department of Rheumatology, Institute of Bone and Joint Research, Level 1, Block 4, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065 Australia. cjackson@med.usyd.edu.au
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Jackson
authors.forename: Meilang
authors.initials: M
authors.lastname: Xue
mesh_terms: D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008954:Models, Biological; D011486:Protein C / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D011486:Protein C