Biosynthesis and Assembly of the Factor VIII-Von Willebrand Factor Complex
Factor VIII and the von Willebrand factor (vWF) are plasma proteins that serve an essential role in the hemostatic proces; factor VIII functions as a cofactor in the intrinsic coagulation pathway (1, 2) whereas vWF is hemostatically important in the mediation of platelet-vessel wall interactions at sites of vascular injury (3, 4). In blood, factor VIII and vWF are not present as distinct proteins but rather circulate as a linked complex. Several lines of evidence indicate that this phenomenon is of physiological significance. For instance, it now seems clear that vWF functions as a carrier protein and as such has a stabilizing effect on factor VIII. This view stems from the observation that reduced or absent synthesis of vWF (as seen in von Willebrand’s disease) is associated with markedly reduced concentrations, or absence, of plasma factor VIII (5). Similarly, a rise in vWF concentration, as observed in disorders associated with acute-phase reactions, is accompanied with concommitant rises in plasma factor VIII concentrations (6). Taken into account that the half life of factor VIII infused in animals is determined by the presence of endogenous vWF (7), and vWF also stabilizes factor VIII in vitro (8), these observations clearly illustrate that vWF not only binds to factor VIII but also confers stability to factor VIII. As vWF protects factor VIII from proteolytic attack by proteases including thrombin and activated factor X (9, 10), it seems likely that limited proteolysis is a factor that determines the stability of factor VIII in vitro and in vivo. The importance of the apparent stabilizing effect of vWF on factor VIII is underscored by recent observations which show that an aberrant interaction between factor VIII and vWF predisposes to a bleeding diathesis (11, 12) Taken together, these observations clearly document the physiological importance of the factor VIII-vWF complex formation.
KeywordsFactor VIII Sinusoidal Endothelial Cell Tyrosine Sulfation Plasma Factor VIII Antihemophilic Factor
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