Factor seven activating protease : in search of a physiological role

Abstract

Since its discovery in 1996, numerous functions have been proposed for Factor VII-activating protease (FSAP) including interactions with the haemostatic system. These include activation of the single chain urokinase-type plasminogen activator (scuPA) and coagulation factor VII (FVII), and interaction with the endothelium and smooth muscle cells. With its decreasing specificity, the physiological role of FSAP has become increasingly unclear. About 5-10 % of apparently healthy individuals carry a FSAP variant (known as “Marburg-1”) which contains a glycine (G) to glutamate (E) substitution located in the catalytic domain. This FSAP variant is associated with a 50-80 % impaired activation of scuPA in vitro, suggesting an effect on fibrinolysis. Epidemiological studies however, vary strongly in their conclusions concerning the implications of this polymorphism. The studies presented in this thesis were performed to assess the role of FSAP in the haemostatic system and the potential pathophysiological implications of the Marburg-1 FSAP polymorphism (G534E) for FSAP biological activity