Role of von Willebrand factor glycans in modulating susceptibility to ADAMTS13 proteolysis

Abstract

Von Willebrand factor (VWF) is a large plasma sialoglycoprotein that mediates platelet tethering at sites of vascular injury. VWF adhesive function is dependent upon multimeric composition, which is regulated in plasma by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13). VWF is synthesised exclusively by endothelial cells and megakaryocytes, resulting in two distinct pools of circulating protein; plasma- and platelet-derived VWF. Previous studies have demonstrated that plasma-VWF N-linked glycans and blood group antigenic carbohydrate structures play a critical role in modulating susceptibility to ADAMTS13 proteolysis. In addition, the glycosylation profile of platelet-VWF differs from that of circulating plasma-VWF.