ArticleBlood2012
von Willebrand factor (VWF) propeptide binding to VWF D'D3 domain attenuates platelet activation and adhesion.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- Assessing primary hemostasis in cirrhosis: not only platelet count.Research and practice in thrombosis and haemostasis · 2026Article
- Total thrombus formation system exploration of primary hemostasis in cirrhotic patients.Research and practice in thrombosis and haemostasis · 2026Article
- Weibel-Palade bodies - secretory organelles at the interface of inflammation and hemostasis.Frontiers in cell and developmental biology · 2025Review
- Chemigenetic Ca2+ indicators report elevated Ca2+ levels in endothelial Weibel-Palade bodies.PloS one · 2025Article
- Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants.Stem cell research & therapy · 2020Article
- FVIII half-life extension by coadministration of a D'D3 albumin fusion protein in mice, rabbits, rats, and monkeys.Blood advances · 2020Article
- von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain.Blood advances · 2019Article
- The physical spacing between the von Willebrand factor D'D3 and A1 domains regulates platelet adhesion in vitro and in vivo.Journal of thrombosis and haemostasis : JTH · 2018Article
- Role of calcium in regulating the intra- and extracellular cleavage of von Willebrand factor by the protease ADAMTS13.Blood advances · 2017Article
- Review
- Segmental outflow of aqueous humor in mouse and human.Experimental eye research · 2017Review
- A systematic analysis of acceptor specificity and reaction kinetics of five human α(2,3)sialyltransferases: Product inhibition studies illustrate reaction mechanism for ST3Gal-I.Biochemical and biophysical research communications · 2016Article
- Article
- [The function and clinical value of Von Willebrand factor propeptide].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- Pathological von Willebrand factor fibers resist tissue plasminogen activator and ADAMTS13 while promoting the contact pathway and shear-induced platelet activation.Journal of thrombosis and haemostasis : JTH · 2015Article
- Role of fluid shear stress in regulating VWF structure, function and related blood disorders.Biorheology · 2015Review
- Platelet GpIba binding to von Willebrand Factor under fluid shear:contributions of the D′D3-domain, A1-domain flanking peptide and O-linked glycans.Journal of the American Heart Association · 2014Article
- Compromised shear-dependent cleavage of type 2N von Willebrand factor variants by ADAMTS13 in the presence of factor VIII.Thrombosis and haemostasis · 2013Article
- Glycoproteomic analysis of the secretome of human endothelial cells.Molecular & cellular proteomics : MCP · 2013Article
- The unfolded von Willebrand factor response in bloodstream: the self-association perspective.Journal of hematology & oncology · 2012Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Noncovalent association between the von Willebrand factor (VWF) propeptide (VWFpp) and mature VWF aids N-terminal multimerization and protein compartmentalization in storage granules. This association is currently thought to dissipate after secretion into blood. In the present study, we examined this proposition by quantifying the affinity and kinetics of VWFpp binding to mature VWF using surface plasmon resonance and by developing novel anti-VWF D'D3 mAbs. Our results show that the only binding site for VWFpp in mature VWF is in its D'D3 domain. At pH 6.2 and 10mM Ca(2+), conditions mimicking intracellular compartments, VWFpp-VWF binding occurs with high affinity (K(D) = 0.2nM, k(off) = 8 × 10(-5) s(-1)). Significant, albeit weaker, binding (K(D) = 25nM, k(off) = 4 × 10(-3) s(-1)) occurs under physiologic conditions of pH 7.4 and 2.5mM Ca(2+). This interaction was also observed in human plasma (K(D) = 50nM). The addition of recombinant VWFpp in both flow-chamber-based platelet adhesion assays and viscometer-based shear-induced platelet aggregation and activation studies reduced platelet adhesion and activation partially. Anti-D'D3 mAb DD3.1, which blocks VWFpp binding to VWF-D'D3, also abrogated platelet adhesion, as shown by shear-induced platelet aggregation and activation studies. Our data demonstrate that VWFpp binding to mature VWF occurs in the circulation, which can regulate the hemostatic potential of VWF by reducing VWF binding to platelet GpIbα.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.