Thrombin vascular injury

Prothrombin (factor II) is a 582 amino acid, 72.5 kDa glycoprotein, which represents the circulating zymogen of thrombin (Ha). It contains up to six y-carboxyglutamate residues towards its N-terminal end, via which it binds several Ca2+ ions. Binding of Ca2+ facilitates prothrombin binding to factor Xa at the site of vascular injury. The factor Xa complex then proteolytically... 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

The role of thrombin in vascular injury. Abbreviation ADP, adenosine diphosphate. 

Stouffer, G. A., Hu, Z., Sajid, M. et al. (1998). Beta 3 integrins are upregulated after vascular injury and modulate thrombospondin- and thrombin-induced proliferation of cultured smooth muscle cells. Circulation 97, 907-915. 

Physiological coagulation (the extrinsic pathway) begins when tissue factor (TF, tissue thromboplastin), exposed by vascular injury, activates and complexes with factor VII to activate factors IX and X which complex with Villa and Va respectively on membrane surfaces (which provide phospholipid, PL). The Xa/Va complex converts prothrombin to thrombin which converts fibrinogen to fibrin and also activates factors XI, VIII, V and XIII, both accelerating coagulation and cross-linking fibrin (-F-F-F-). 

In response to vascular injury, the body must tightly seal the leakage while preventing unrestrained intravascular clot development and vessel occlusion. The coagulation process is a complex interplay of the blood vessel wall, platelets and other blood cells, as well as many soluble plasma proteins ( coagulation factors [16]). In the ultimate step of the coagulation cascade, the trypsin-hke serine proteinase thrombin (factor Ila) is released into the blood stream, where it performs several es-... 

Prothrombin, thromhogen, factor II, the zymogen of the serine protease thrombin. Prothrombin occurs in all vertebrates, and is activated after initiation of the coagulation cascade at the site of vascular injury. Prothrombin consists of the thrombin domain, a Gla domain, and two kringle domains [J. Stenflo et al., Proc. Natl. Acad. Sci. USA 1974, 72, 2730 K. G. Mann et al.. Methods Enzymol. 1981, 80, 286]. 

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