Thrombin and fibrinolysis.
When the activities of the coagulation and fibrinolytic cascades are properly regulated, so that fibrin (FN) deposition and removal are properly balanced, the vascular system is protected from catastrophic blood loss at the site of an injury, while its fluidity is ensured elsewhere. When these activities are not properly regulated, however, the organism is subjected to either excessive bleeding or thrombosis. Thrombomodulin on the endothelial cell is very important in this regulation because it converts thrombin to an anticoagulant enzyme by directing it toward the activation of protein C. It also converts thrombin to an antifibrinolytic enzyme by directing it toward the activation of thrombin-activatable fibrinolysis inhibitor (TAFI). By doing so, it creates a direct molecular connection between the coagulation and fibrinolytic cascades, such that activation of the former suppresses the activity of the latter. Recent studies indicate that the TAFI pathway functions in vivo and is likely relevant in maintaining the proper balance between FN deposition and removal. Whether it will be a target for pharmaceutical manipulation of this balance remains to be determined.
Nesheim
Michael
M
Departments of Biochemistry and Medicine, Queen's University, Kingston, ON, Canada. nesheimm@post.queensu.ca
D001777:Blood Coagulation / Q000502:physiology; D025901:Carboxypeptidase B2 / Q000235:genetics / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D013917:Thrombin / Q000502:physiology*
D025901:Carboxypeptidase B2; D013917:Thrombin