What is the role of thrombomodulin?
Thrombomodulin (TM), a high affinity thrombin receptor present on endothelial cell membrane, plays an important role as a natural anticoagulant. It acts as a cofactor of thrombin-catalyzed activation of protein C, and inhibits the procoagulant functions of thrombin.
Is thrombomodulin a clotting factor?
Thrombomodulin is a protein found on the surface of cells lining the blood vessels. It acts as an attachment point for thrombin and plays an important role in blood clotting and clot breakdown. Thrombomodulin-bound thrombin initiates the protein C anticoagulant pathway by activating protein C.
Where does thrombomodulin come from?
Thrombomodulin (TM), a cell surface-expressed glycoprotein, predominantly synthesized by vascular endothelial cells, is a critical cofactor for thrombin-mediated activation of protein C (PC), an event further amplified by the endothelial cell protein C receptor (EPCR).
Is thrombomodulin an antithrombin?
Modulators of Coagulation Coagulation is modulated by a number of other plasma proteins, the most important of which are antithrombin III, thrombomodulin, TF pathway inhibitor, protein C, protein S, and factor V. Antithrombin III is a potent inhibitor of thrombin, factors IXa and Xa, and XIIIa.
How thrombomodulin affects coagulation process?
Anticoagulant Properties of Thrombomodulin TM directly inhibits most of the procoagulant functions of thrombin including fibrinogen clotting, platelet and EC activation, and FV activation [36, 37]. In addition, TM accelerates the inactivation of thrombin via both antithrombin and protein C inhibitor [54, 55].
Is thrombomodulin vitamin K dependent?
Protein C is a vitamin K–dependent protein that binds to thrombomodulin, an endothelial cell surface protein, and is converted to an active protease by the action of thrombin.
How does thrombomodulin mediate its anticoagulant effect?
Thrombomodulin is an endothelial cell thrombin receptor that converts thrombin into an anticoagulant capable of activating protein C, suggesting a protective role in thrombosis.
Is thrombomodulin vitamin K-dependent?
Is thrombomodulin a protein C?
Protein C is a multidomain vitamin K-dependent plasma serine protease zymogen that, upon activation by thrombin in complex with thrombomodulin (TM), down-regulates the coagulation cascade by inactivating factors Va and VIIIa by limited proteolysis (1–3).
Which protein acts as an anticoagulant?
Proteins C and S are two vitamin K-dependent plasma proteins that work in concert as a natural anticoagulant system.
What is Thrombomodulin (TM)?
Thrombomodulin (TM) is a membrane protein, which consists of five domains (TMD1, TMD2, TMD3, TMD4, and TMD5) and serves as a receptor for thrombin inhibiting its procoagulant activity on the surface of vascular endothelial cells.
Is protein S deficiency associated with venous thrombosis?
Protein S deficiency is associated with venous thrombosis and mutations give rise to rare forms of familial venous thrombosis. Common polymorphisms of the protein S gene include Pro626 and the 2698 C/A polymorphisms which associate with plasma levels of protein S antigen.
What happens if thrombin is not present in endothelial cells?
Loss of TM is a prominent feature of postradiation endothelial dysfunction. In the absence of TM, thrombin acts as a proinflammatory and profibrotic mediator, in part through the activation of the proteinase-activated receptor-1 [98–100].
What happens to thrombin when it is bound to TM?
When bound to TM, thrombin loses its procoagulant, proinflammatory, and profibrogenic properties and instead acquires the ability to activate protein C (APC). APC limits further thrombin generation, counteracts thrombin’s adverse effects [95], and has additional antiinflammatory and cytoprotective properties [96].