Published online before print August 25, 2005, doi: 10.1161/01.ATV.0000183884.06371.52
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© 2005 American Heart Association, Inc.
Brief Reviews |
Tissue-Specific Hemostasis in Mice
From the Scripps Research Institute, Departments of Immunology and Cell Biology, La Jolla, Calif.
Correspondence to Nigel Mackman, PhD, Scripps Research Institute, Departments of Immunology and Cell Biology, 10550 N Torrey Pines Rd, CVN-18, La Jolla, CA 92037. E-mail nmackman{at}scripps.edu
Blood coagulation is essential to maintain hemostasis in organisms with a vascular network. Formation of a fibrin-rich clot at a site of vessel injury is a highly complex process that is orchestrated by the coagulation protease cascade. This cascade is regulated by 3 major anticoagulant pathways. Removal of a clot is mediated by the fibrinolytic system. Defects in the regulation of clot formation lead to either hemorrhage or thrombosis. Tissue factor, the primary cellular initiator of blood coagulation, is a transmembrane receptor that is expressed in a tissue-specific manner. The 3 major anticoagulants are tissue factor pathway inhibitor, antithrombin, and protein C, the latter requiring a transmembrane receptor called thrombomodulin for its activation. Tissue factor pathway inhibitor and thrombomodulin are expressed by endothelial cells in a tissue-specific manner, whereas antithrombin and protein C circulate in the plasma. Fibrinolysis requires the activation of plasminogen to plasmin, which is mediated by tissue-type plasminogen activator and urokinase-type plasminogen activator. Interestingly, tissue-type plasminogen activator is expressed by a subset of endothelial cells of discrete size and location. These observations, together with the phenotypes of mice that have defects in the procoagulant, anticoagulant, and fibrinolytic pathways, indicate that hemostasis is regulated in a tissue-specific manner.
Formation of a fibrin-rich clot is regulated by the coagulation, anticoagulation, and fibrinolytic pathways. Decreased fibrin is associated with bleeding, whereas increased fibrin leads to thrombosis. Analysis of mice with defects in clot formation suggests that hemostasis is regulated in a tissue-specific manner.
Key Words: coagulation • anticoagulants • fibrinolysis
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