[Anti-thrombotic effect of activated protein C].
Protein C (PC) is an important anticoagulant protein in blood and converted to its active form, activated protein C (APC), by thrombin bound with thrombomodulin. APC exhibits an anticoagulant effect by the inactivation of FV a and FVIII a. In addition, APC exerts a profibrinolytic effect by inactivation of PAI-1 and inhibition of TAFI activation. APC is strongly anti-thrombotic because of its anticoagulant and profibrinolytic effect. APC has gamma-carboxyglutamic acid residues that bind to acidic phospholipids expressed on activated platelet or injured endothelial cells. Thus APC works only at the site where clots are formed and has a weak effect in primary hemostasis; this means that the use of APC is expected not to have any hemorrhagic risk. In both DIC animal models and clinical studies, we confirmed safer amelioration by APC than heparin. Recently, a specific receptor for PC/APC was found on endothelial cell membrane and anti-inflammatory effects of APC were also reported. Thus APC is thought to play an important regulatory role in blood coagulation, fibrinolysis and inflammation, especially in thrombotic diseases.
Katsuura
Y
Y
Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Limited, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan. y.katuura@teijin.co.jp
D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents; D001779:Blood Coagulation Factors / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy; D004730:Endothelium, Vascular; D005343:Fibrinolytic Agents; D006470:Hemorrhage; D006801:Humans; D008969:Molecular Sequence Data; D011486:Protein C / Q000494:pharmacology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000502:physiology; D012306:Risk
D000893:Anti-Inflammatory Agents; D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D011486:Protein C; D011956:Receptors, Cell Surface; C091963:activated protein C receptor