Annexin 2/Factor Xa–Mediated Signal Transduction
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See related article, pages 457–464
In this issue of Circulation Research, Bhattacharjee et al1 provide evidence that annexin 2 may be important in the ability of factor Xa to induce signal transduction dependent on protease-activated receptor (PAR)-1. The significance of these observations must be considered in the context of broader questions related to thrombosis and fibrinolysis. In the first decade of the 20th century, knowledge of blood coagulation resulted in a relatively simple model. In 1905, Morowitz proposed that the coagulation cascade consists of 4 fluid phase components of blood.2 The 4 components involved in coagulation were identified as fibrinogen, Ca2+, prothrombin, and “tissue thromboplastin.” He also recognized that platelets and perhaps leukocytes played a role in blood clotting.2 Tissue thromboplastin was identified as a lipid- and protein-containing component of tissues that was released during vascular injury. In the presence of Ca2+, this substance activated prothrombin. The resultant thrombin converted fibrinogen to fibrin. The discovery of “factor V” in 1943 expanded the model of coagulation beyond these 4 components and triggered a search for other coagulation factors. During the 20th century, many more such factors were discovered. Most of these received factor numbers, whereas some were known more commonly by name. The concept arose that there were 2 pathways of coagulation, namely, the intrinsic and extrinsic systems. It was believed that the intrinsic pathway was most important at the surface of damaged blood vessels, whereas the extrinsic system became activated after major vascular injury causing the release of tissue thromboplastin or, as it became known, tissue factor (TF). Both the extrinsic and intrinsic systems were seen as converging at the point where factor X was activated and this factor Xa was responsible for the activation of prothrombin. The 2 systems were …