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Tissue-specific hemostasis in mice

Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 5.53). 12/2005; 25(11):2273-81. DOI: 10.1161/01.ATV.0000183884.06371.52
Source: PubMed

ABSTRACT 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.

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    • "Thrombosis plays a critical role in the development of cardiovascular diseases (Sturm 2004) and may be caused by the upregulation of the procoagulant pathway, or the downregulation of anticoagulant and fibrinolytic pathways (Mackman 2005). Thrombotic risk has been associated with genetic variation in these three pathways (Grant 2003; Williams and Bray 2001). "
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    • "Inappropriate activation of the coagulation pathways, however, can promote intravascular thrombosis (Chu 2006; Mackman 2005). The blood coagulation cascade is composed of intrinsic and extrinsic pathways. "
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