Abstract
Multimeric glycoprotein von Willebrand factor (VWF) exhibits a unique triplet structure
of individual oligomers, resulting from ADAMTS-13 (a disintegrin and metalloproteinase
with thrombospondin type 1 motifs 13) cleavage. The faster and slower migrating triplet
bands of a given VWF multimer have one shorter or longer N-terminal peptide sequence,
respectively. Within this peptide sequence, the A1 domain regulates interaction of
VWF with platelet glycoprotein (GP)Ib. Therefore, platelet-adhesive properties of
two VWF preparations with similar multimeric distribution but different triplet composition
were investigated for differential functional activities. Preparation A was enriched
in intermediate triplet bands, whereas preparation B predominantly contained larger
triplet bands. Binding studies revealed that preparation A displayed a reduced affinity
for recombinant GPIb but an unchanged affinity for collagen type III when compared
to preparation B. Under high-shear flow conditions, preparation A was less active
in recruiting platelets to collagen type III. Furthermore, when added to blood from
patients with von Willebrand disease (VWD), defective thrombus formation was less
restored. Thus, VWF forms lacking larger-size triplet bands appear to have a decreased
potential to recruit platelets to collagen-bound VWF under arterial flow conditions.
By implication, changes in triplet band distribution observed in patients with VWD
may result in altered platelet adhesion at high-shear flow.
Keywords
collagen - flow - glycoprotein Ib - von Willebrand factor triplets - platelet adhesion
