Defining the roles of von Willebrand Factor and Factor V111 glycosylation in regulating lectin interaction and modulating in vivo clearance

Abstract

von Willebrand Factor (VWF) is a large multimeric sialoglycoprotein which mediates critical roles in normal haemostasis. VWF tethers platelets at sites of vascular injury and also serves as a chaperone for coagulation factor VIII (FVIII). Both VWF and FVIII are extensively glycosylated, with N- and 0-linked carbohydrates structures constituting approximately 20% of their molecular mass. Importantly, these glycans have been shown to influence VWF and FVIII biology. However the molecular mechanisms through which these glycan structures serve to modulate VWF and FVIII physiology remains poorly understood. In this context, the ability of VWF and FVIII to interact with lectins is likely to play an important role. Recently VWF has been shown to circulate in plasma complexed with specific lectins galectin-1 and galectin-3. Moreover, this interaction was found to directly modulate VWF-dependent early thrombus formation in vivo. On this basis, we sought to define the molecular basis underlying the VWF- galectin-1 interaction.