Affinage

VWF

von Willebrand factor · UniProt P04275

Round 2 corrected
Length
2813 aa
Mass
309.3 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VWF is a large multimeric glycoprotein produced by endothelial cells and megakaryocytes that serves as the primary adhesive bridge between platelets and damaged vessel walls under high shear stress and as the plasma carrier and stabilizer of coagulation factor VIII (PMID:9759493, PMID:10881749). Synthesized as a pre-pro-polypeptide (D1-D2-D'-D3-A1-A2-A3-D4-B-C domains), VWF requires its propeptide (D1-D2) as an intramolecular chaperone for disulfide-linked multimerization in the ER, after which furin cleaves the propeptide; ultra-large multimers are stored in endothelial Weibel-Palade bodies—organelles whose biogenesis depends on VWF itself and accessory machinery including BLOC-2, the exocyst complex, and Rab27a/MyRIP—and are released upon stimulation to form platelet-catching strings whose size is homeostatically regulated by shear-dependent A2-domain unfolding and ADAMTS13 cleavage, itself modulated by chloride binding, N-glycosylation at N1574, and thrombospondin-1 competition (PMID:3500851, PMID:2251280, PMID:15331450, PMID:32614949, PMID:19498171, PMID:16899464, PMID:17975018). The A1 domain mediates GPIbα catch-slip bond adhesion—regulated allosterically by propeptide binding to D'D3 and by A1-domain conformational state—activating platelet signaling through Lyn–cGMP and Lyn/Syk/Btk–TxA₂ cascades, while the A3 domain engages fibrillar collagen at its hydrophobic front surface (PMID:8565074, PMID:12183630, PMID:22452980, PMID:15941906, PMID:16788103, PMID:12447349). Beyond hemostasis, VWF restrains endothelial angiogenesis via VEGFR-2 and Ang-2, promotes vascular smooth muscle cell proliferation through an A2–LRP4–αvβ3 axis, maintains endothelial barrier integrity during neutrophil extravasation via platelet-derived Angpt1–Tie-2 signaling, and is cleared from plasma by macrophage/Kupffer cell LRP1 through A1-domain residues K1405–K1408 (PMID:21048155, PMID:33576766, PMID:32369573, PMID:38996211).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1985 High

    Isolation and chromosomal mapping of VWF cDNA established its identity as an endothelial-cell-derived gene on chromosome 12p, providing the molecular foundation for dissecting VWF structure and disease mutations.

    Evidence cDNA library screening from endothelial cells with in situ hybridization mapping

    PMID:2864688 PMID:3874428

    Open questions at the time
    • Promoter elements and transcriptional regulation not yet defined
    • Megakaryocyte expression not characterized at this stage
  2. 1986 High

    Full-length sequencing revealed VWF's complete domain architecture (D1-D2-D'-D3-A1-A2-A3-D4-B-C), glycosylation map, and dual secretory pathways—constitutive (dimeric) vs. regulated (ultra-large multimers from Weibel-Palade bodies)—establishing the framework for understanding how domain structure relates to hemostatic function.

    Evidence Complete cDNA/protein sequencing, in vitro expression in COS-1 cells, immunoelectron microscopy of WPBs, stimulated secretion assays

    PMID:3019665 PMID:3087627 PMID:3524673 PMID:6754744

    Open questions at the time
    • Mechanism of WPB biogenesis unknown
    • Signals governing regulated exocytosis undefined
  3. 1987 High

    The propeptide (D1-D2) was shown to be required for multimerization beyond the dimer stage, functioning as an intramolecular chaperone, while N-glycosylation was found necessary for efficient ER exit—defining two critical quality-control steps in VWF biosynthesis.

    Evidence Propeptide-deleted VWF expression in COS-1 cells; tunicamycin treatment and BiP co-immunoprecipitation in CHO cells

    PMID:3121636 PMID:3500851

    Open questions at the time
    • Structural basis of propeptide-assisted multimerization unresolved
    • Disulfide isomerase(s) mediating interchain bonds not identified
  4. 1990 High

    Identification of furin/PACE as the enzyme cleaving the VWF propeptide resolved the maturation step linking pro-VWF to circulating multimers.

    Evidence Co-expression of PACE cDNA with VWF precursor in COS-1 cells

    PMID:2251280

    Open questions at the time
    • Compartment-specific timing of cleavage relative to multimerization not established
    • Whether other proprotein convertases contribute in vivo
  5. 1996 High

    Two breakthrough findings—that GPIbα supports fast-on/fast-off platelet tethering under high shear and that VWF undergoes a shear-induced globular-to-extended conformational transition—explained how VWF functions as a mechanosensitive adhesive molecule.

    Evidence Flow chamber assays with blocking antibodies; atomic force microscopy under controlled shear

    PMID:8565074 PMID:8874190

    Open questions at the time
    • Molecular basis of catch bond not yet defined
    • Which domains unfold first under shear unknown
  6. 2002 High

    Crystal structure of the GPIbα–VWF A1 complex revealed the atomic interface underlying platelet adhesion, while a patient D1-domain mutation (Tyr87Ser) confirmed the propeptide's chaperone role for multimerization and downstream functions.

    Evidence X-ray crystallography of GPIbα–A1 complex; patient mutation with recombinant VWF expression and binding assays

    PMID:12176890 PMID:12183630

    Open questions at the time
    • How flanking domains modulate A1–GPIbα affinity in full-length VWF
    • Structural mechanism of propeptide-assisted disulfide bonding
  7. 2003 High

    NMR mapping of the A3 domain–collagen interface to a hydrophobic 'front' surface identified a binding mode distinct from integrin α2-I domains, defining VWF's collagen-recognition mechanism at atomic resolution.

    Evidence Transferred cross-saturation NMR on A3–fibrillar collagen complex

    PMID:12447349

    Open questions at the time
    • Relative contributions of collagen types I vs III in vivo not resolved
    • Structural basis of A3–A1 cooperativity unknown
  8. 2004 High

    Reconstitution of WPB biogenesis by re-expression of VWF in VWF-null endothelial cells proved that VWF itself drives WPB formation, recruiting P-selectin and other cargo, establishing VWF as the organizing molecule of its own storage organelle.

    Evidence Lentiviral VWF re-expression in canine VWD endothelial cells, confocal immunofluorescence

    PMID:15331450

    Open questions at the time
    • Minimal VWF domain requirements for WPB nucleation not defined
    • Cargo sorting signals for other WPB residents unclear
  9. 2005 High

    Systematic epistasis analysis using knockout mouse platelets placed Lyn, Syk, SLP-76, PI3K, PLCγ2, and Btk in a GPIbα–VWF-triggered signaling cascade leading to TxA₂ production, and identified 14-3-3ζ as an allosteric regulator of GPIb-IX VWF-binding function.

    Evidence Multiple KO mouse platelet systems, pharmacological inhibitors, ristocetin agglutination, flow adhesion

    PMID:15941906 PMID:15985541

    Open questions at the time
    • How GPIbα mechanotransduction initiates Lyn activation at the membrane
    • Role of LAT and FcRγ in granule secretion vs TxA₂ not fully separated
  10. 2006 High

    Discovery that chloride ions bind to the VWF A1 domain and allosterically inhibit ADAMTS13 cleavage of the A2 domain revealed an ionic regulatory mechanism for multimer size control, with disease mutation R1306W reducing chloride affinity.

    Evidence ITC, urea-unfolding spectroscopy, ADAMTS13 cleavage assays on isolated domains

    PMID:16899464

    Open questions at the time
    • Physiological chloride concentration fluctuations at sites of hemostasis not characterized
    • Structural basis of allosteric transmission from A1 chloride site to A2 cleavage site
  11. 2007 High

    Site-directed mutagenesis demonstrated that N-glycosylation at N1574 sterically inhibits ADAMTS13 cleavage of VWF, providing a molecular explanation for ABO blood group influence on VWF multimer size and thrombosis risk.

    Evidence PNGaseF digestion and N-glycosylation-site mutagenesis in recombinant VWF, ADAMTS13 binding/cleavage assays

    PMID:17975018

    Open questions at the time
    • Precise structural model of how the glycan at N1574 shields the cleavage site
    • Whether O-glycans also regulate cleavage
  12. 2009 High

    Single-molecule force spectroscopy proved that elongational shear forces unfold the VWF A2 domain in a size-dependent manner (force scales with multimer length squared), with only the unfolded state being an ADAMTS13 substrate—establishing the homeostatic force-cleavage mechanism.

    Evidence Optical tweezers on single VWF molecules, ADAMTS13 cleavage of mechanically unfolded A2

    PMID:19498171

    Open questions at the time
    • In vivo force measurements at the single-multimer level not achieved
    • Contribution of A2 refolding kinetics to net cleavage rate
  13. 2009 High

    Rab27a and MyRIP were identified as peripheral actin anchors for WPBs, controlling both distribution and release; their depletion caused premature secretion of less-multimerized VWF, linking WPB positioning to VWF quality.

    Evidence siRNA depletion in primary endothelial cells, live imaging, VWF multimer analysis, flow string assays

    PMID:19270261

    Open questions at the time
    • How Rab27a senses stimulatory signals to release the WPB anchor
    • Whether MyoVa motor also participates
  14. 2010 High

    VWF was revealed to regulate endothelial angiogenesis: VWF deficiency causes increased VEGFR-2-dependent proliferation, elevated Ang-2 release, and enhanced vascularization, establishing a non-hemostatic vascular role for VWF.

    Evidence siRNA in HUVECs, VWD patient-derived EPCs, in vitro tube formation, VWF-null mouse vascularization models

    PMID:21048155

    Open questions at the time
    • Mechanism by which intracellular VWF restrains Ang-2 secretion not fully defined
    • Whether therapeutic VWF replacement reverses angiogenic phenotype in VWD patients
  15. 2012 High

    Quantitative SPR showed VWF propeptide persists bound to D'D3 in plasma (KD ~25–50 nM), attenuating GPIbα engagement—revealing an unexpected circulating regulatory mechanism for VWF platelet adhesion beyond simple propeptide removal.

    Evidence Surface plasmon resonance with anti-D'D3 mAbs, shear-induced platelet aggregation, flow chamber assays

    PMID:22452980

    Open questions at the time
    • Fraction of circulating VWF bearing propeptide in vivo unknown
    • Whether propeptide dissociation is shear-dependent
  16. 2014 High

    Knock-in mouse models of A1-domain mutations at two distinct GPIbα contact surfaces demonstrated that the kinetic balance between catch and slip bond regimes dictates the hemostatic-thrombotic boundary, with compensatory double mutations normalizing function.

    Evidence VWF-A1 knock-in mice (I1309V, R1326H, double), intravital microscopy, tail bleeding, flow adhesion

    PMID:25293780

    Open questions at the time
    • How flanking domains (D'D3, A2) modulate catch-slip kinetics in full-length VWF
    • Whether therapeutic tuning of bond kinetics is feasible
  17. 2020 High

    BLOC-2 and the exocyst complex were identified as two independent regulators of WPB biogenesis that together control VWF multimer maturation and exocytosis, closing a major gap in the WPB formation pathway.

    Evidence siRNA depletion, reciprocal co-IP of BLOC-2–exocyst, VWF multimer analysis, Endosidin2 pharmacological validation

    PMID:32614949

    Open questions at the time
    • How BLOC-2 mediates endosomal input into WPBs
    • Whether exocyst 'clamping' is relieved by specific stimulatory signaling
  18. 2020 High

    VWF was shown to maintain vascular barrier integrity during inflammation by serving as the platform for platelet docking, which delivers Angpt1 to activate endothelial Tie-2 via Cdc42-GEF FGD5, preventing leaks during neutrophil transmigration.

    Evidence Endothelial Tie-2 KO, platelet Angpt1 conditional KO, intravital microscopy, anti-VWF antibody blocking

    PMID:32369573

    Open questions at the time
    • Whether this pathway operates in non-inflamed tissues
    • Relative contributions of endothelial vs platelet Angpt1
  19. 2022 High

    VWF A2 domain binding to LRP4 receptor, signaling through αvβ3 integrin, was identified as a mechanism by which VWF promotes vascular smooth muscle cell proliferation and intimal hyperplasia, extending VWF's role beyond hemostasis to vascular remodeling.

    Evidence siRNA against LRP4 and αv integrin, co-IP, proximity ligation assay, VWF-KO mouse arterial injury models

    PMID:33576766

    Open questions at the time
    • Whether A2 domain must be unfolded for LRP4 engagement
    • Downstream transcriptional targets in VSMC not identified
  20. 2024 High

    The VWF clearance mechanism was molecularly defined: A1-domain residues K1405–K1408 mediate binding to macrophage LRP1, and endothelial PTP1B was identified as a negative regulator of WPB exocytosis acting through SNAP23 dephosphorylation—completing both clearance and release arms of VWF homeostasis.

    Evidence Alanine mutagenesis of K1405–K1408 with in vivo clearance, BT200 aptamer competition; endothelial PTP1B-KO mice with SNAP23 phosphorylation assays and intravital microscopy

    PMID:38563147 PMID:38996211

    Open questions at the time
    • Relative contribution of MGL and SR-AI vs LRP1 to total VWF clearance in humans
    • Whether PTP1B–SNAP23 axis is targetable therapeutically without off-target effects

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of propeptide-assisted interchain disulfide bonding during multimerization; how VWF intracellularly suppresses Ang-2/VEGFR-2 angiogenic signaling; the in vivo force landscape experienced by individual VWF multimers; and whether the non-hemostatic functions (angiogenesis, VSMC proliferation, barrier maintenance) are therapeutically separable from hemostatic activity.
  • No high-resolution structure of full-length multimeric VWF
  • Mechanism of intracellular VWF-mediated angiogenesis suppression undefined
  • Therapeutic strategies separating hemostatic from non-hemostatic VWF functions not developed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0005198 structural molecule activity 4 GO:0048018 receptor ligand activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005576 extracellular region 5 GO:0031410 cytoplasmic vesicle 5 GO:0005783 endoplasmic reticulum 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-109582 Hemostasis 10 R-HSA-162582 Signal Transduction 6 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-1474244 Extracellular matrix organization 3
Partners
ADAMTS13F8GP1BALRP1LRP4MYRIPRAB27ASNAP23
Complex memberships
GPIb-IX-V complex (VWF ligand)VWF–FVIII complexWeibel-Palade body

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 VWF cDNA clones spanning 8.2 kb of mRNA were isolated from human endothelial cells; the VWF gene was localized to chromosome 12p12-12pter, and VWF accounts for ~0.3% of endothelial cell mRNA. cDNA library screening, chromosomal localization by in situ hybridization Science High 3874428
1985 VWF cDNA encodes a precursor protein with a signal peptide, propeptide, and mature subunit; the carboxyl-terminal portion contains internal gene duplications and the cell-attachment tetrapeptide Arg-Gly-Asp-Ser. cDNA cloning and sequencing, amino acid sequence comparison Proceedings of the National Academy of Sciences of the United States of America High 2864688
1986 Full-length VWF cDNA encodes a single-chain precursor of 2813 amino acids with a signal peptide (22 aa), prosequence (741 aa, domains D1-D2), and mature VWF (2050 aa); the domain structure is D1-D2-D'-D3-A1-A2-A3-D4-B1-B2-C1-C2; in vitro expression confirmed synthesis of the unglycosylated precursor. Full-length cDNA assembly and in vitro expression in COS-1 cells The EMBO journal High 3019665
1986 The amino acid sequence of mature VWF (2050 residues) was determined; it contains 12 Asn-linked and 10 Thr/Ser-linked oligosaccharide chains, and shows homology to complement factor B. Direct protein sequencing (Edman degradation) combined with cDNA-derived sequence Biochemistry High 3524673
1986 VWF is localized to Weibel-Palade bodies in human endothelial cells; constitutively secreted VWF is predominantly dimeric with pro-VWF subunits, whereas inducible secretion (by thrombin or calcium ionophore) releases only very large multimers of mature subunits that are more active in platelet binding. Immunofluorescence, immunoperoxidase/electron microscopy, stimulated secretion assays Cell High 3087627 6754744
1987 The VWF propeptide (domains D1-D2) is required for multimerization beyond the dimer stage: COS-1 cells expressing a propeptide-deleted VWF cDNA produce only dimers, demonstrating that dimerization is propeptide-independent but multimerization requires the propeptide. Heterologous expression of full-length and propeptide-deleted VWF cDNA in COS-1 cells The EMBO journal High 3500851
1987 N-linked glycosylation of VWF is required for efficient secretion; VWF transiently associates with BiP (heavy chain-binding protein) during biosynthesis in CHO cells, and this association dissipates as the protein is glycosylated and secreted. Tunicamycin treatment, co-immunoprecipitation of BiP with VWF in CHO cells The Journal of cell biology High 3121636
1989 The VWF gene spans ~178 kb and contains 52 exons (40 bp to 1379 bp); the signal peptide and propeptide are encoded by 17 exons in ~80 kb, and the mature subunit by 35 exons in ~100 kb; domain-encoding exon structure supports origin by gene segment duplication. Cosmid library screening, restriction mapping, complete sequencing of exon-intron boundaries The Journal of biological chemistry High 2584182
1990 PACE (Paired basic Amino acid Cleaving Enzyme, later furin) cleaves the VWF propeptide at the paired basic amino acid site (Arg-Ser cleavage site); co-expression of PACE with VWF in COS-1 cells enhanced propeptide processing. cDNA cloning of PACE, co-expression with VWF precursor in COS-1 cells Proceedings of the National Academy of Sciences of the United States of America High 2251280
1996 GPIbα binding to immobilized VWF supports fast-on/fast-off platelet tethering and translocation at shear rates >6000 s⁻¹; this mechanism allows subsequent αIIbβ3 activation and firm arrest on VWF, coupling two distinct adhesion mechanisms. Flow chamber assays with defined shear rates, blocking antibodies and glycoprotein-deficient platelets Cell High 8565074
1996 VWF undergoes a shear-stress-induced conformational transition from a globular (~149×77 nm) to an extended chain conformation at a critical shear stress of ~35 dyn/cm², with exposure of intramolecular globular domains; this structural change is directional, aligned with shear. Atomic force microscopy of VWF on hydrophobic surfaces under defined shear stress Blood High 8874190
1998 VWF mediates platelet adhesion through binding to platelet GPIb and to subendothelial connective tissue components; VWF also serves as carrier for factor VIII, protecting it from proteolytic degradation; VWF multimer size is regulated by ADAMTS13-like proteolysis and allosteric mechanisms involving hydrodynamic shear. Comprehensive biochemical review synthesizing purification, binding, and mutagenesis data Annual review of biochemistry High 9759493
1999 Non-activated FVIII circulates in a complex with VWF; upon thrombin- or FXa-mediated activation, FVIII dissociates from VWF with concomitant conformational change in the C2 domain, dramatically increasing FVIII affinity for phospholipid surfaces and enabling factor Xase complex assembly. In vitro proteolysis, binding assays with phospholipid vesicles, domain mutagenesis Trends in cardiovascular medicine High 10881749
2001 The A3 domain of VWF mediates collagen binding; a Ser968Thr substitution in the A3 domain abolishes collagen binding while preserving VWF multimeric structure and GPIb binding, identifying Ser968 as critical for collagen interaction. Site-directed mutagenesis of full-length VWF cDNA, transient expression in COS-7 cells, collagen binding assays Thrombosis and haemostasis High 11583318
2002 The D1 domain of the VWF propeptide is critical for N-terminal multimerization; a Tyr87Ser mutation in D1 results in predominantly dimeric VWF with loss of collagen binding, factor VIII binding, and ristocetin-induced platelet binding, but normal granular storage, indicating the propeptide acts as an intramolecular chaperone for multimerization. Patient mutation identification, recombinant VWF expression, multimer analysis, functional binding assays Blood High 12176890
2002 Crystal structures of GPIbα amino-terminal domain and its complex with VWF A1 domain revealed that GPIbα wraps around one side of A1 at two contact areas bridged by solvated charge interactions; gain-of-function mutations in bleeding disorders map to these interfaces. X-ray crystallography of GPIbα alone and GPIbα–VWF A1 complex Science High 12183630
2003 The collagen-binding site of the VWF A3 domain is located on its hydrophobic 'front' surface, as determined by transferred cross-saturation NMR; this binding surface is distinct from the 'top' surface used by the integrin α2-I domain despite shared fold and function. Transferred cross-saturation NMR on A3 domain–fibrillar collagen complex Nature structural biology High 12447349
2003 VWF–FVIII complex bound with VWF is cleared predominantly by Kupffer cells/macrophages in the liver; free FVIII unbound from VWF is cleared by hepatocytes via a VWF-independent pathway. Pharmacokinetic studies, immunohistochemistry in VWF-null mice, FcRn chimeric mice PloS one Medium 25905473
2004 VWF is essential for Weibel-Palade body (WPB) biogenesis in endothelial cells; re-expression of wild-type VWF in VWF-null canine aortic endothelial cells restored WPBs that recruited endogenous P-selectin; VWF multimerization is not required for WPB creation, but the propeptide alone cannot independently induce granule formation. Canine VWD endothelial cell model, lentiviral re-expression, confocal immunofluorescence Blood High 15331450
2005 14-3-3ζ binding to the cytoplasmic tail of GPIbα (and GPIbβ) regulates the VWF-binding function of the GPIb-IX complex; a membrane-permeable inhibitor of 14-3-3ζ–GPIbα interaction potently inhibited VWF binding to platelets and VWF-mediated platelet adhesion under flow. Membrane-permeable inhibitor peptide, mutagenesis of 14-3-3ζ binding site in GPIbβ, flow adhesion assays, ristocetin agglutination Blood High 15941906
2005 GPIb-IX-mediated botrocetin/VWF agglutination triggers TxA2 production via a signaling cascade initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K, PLCγ2, and PKC; LAT and FcRγ-chain are not required for TxA2 production but are required for granule secretion. Genetic knockout mouse platelets (Lyn, Src, Syk, SLP-76, PLCγ2, LAT, FcRγ), pharmacological inhibitors, wortmannin Blood High 15985541
2005 Platelets contain functionally active ADAMTS13 on their surface; platelet ADAMTS13 activity increases upon thrombin receptor-activating peptide (but not ADP) stimulation, and can cleave endothelial-derived ultra-large VWF multimers under static and flow conditions. Platelet lysate VWF cleavage assays, ADAMTS13 antibody inhibition, flow cytometry for surface ADAMTS13 Journal of thrombosis and haemostasis High 16176307
2006 Bruton tyrosine kinase (Btk) is required for GPIb-mediated VWF-induced platelet signaling leading to TxA2 production; Btk acts downstream of Lyn, Syk, SLP-76, and PI3K, and upstream of ERK1/2, PLCγ2, and PKC; Btk is also essential for GPIb-dependent arterial thrombus formation in vivo. Btk-knockout and Tec-knockout mouse platelets, ferric chloride carotid artery injury model, kinase inhibitors Blood High 16788103
2006 Chloride ions bind specifically to the VWF A1 domain (not A2), stabilizing its folded conformation and allosterically inhibiting ADAMTS13-mediated cleavage of the Tyr1605-Met1606 bond in the A2 domain; the R1306W type 2B VWD mutation reduces chloride affinity for the A1 domain. Urea-induced unfolding spectroscopy, isothermal titration calorimetry, ADAMTS13 cleavage assays with isolated VWF domains The Journal of biological chemistry High 16899464
2007 N-linked glycans at VWF residue N1574 (but not N1515) sterically inhibit ADAMTS13-mediated cleavage; removal of N-linked glycans (PNGaseF) increases VWF affinity for ADAMTS13 ~4-fold and allows cleavage without urea denaturation; ABO(H) blood group sugars occupy N1515 and N1574. PNGaseF digestion, site-directed mutagenesis of N-glycosylation sites in recombinant VWF and isolated A2 domain, ADAMTS13 binding/cleavage assays Blood High 17975018
2008 Src family kinase Lyn mediates VWF/GPIb-IX-induced stable platelet adhesion under shear stress via elevation of cGMP independently of TxA2 synthesis; Fyn mediates the TxA2-dependent second wave of aggregation but not stable adhesion; low-concentration 8-bromo-cGMP corrects Lyn-KO adhesion defect. Lyn-KO and Fyn-KO mouse platelets, flow adhesion on VWF, cGMP measurements, 8-bromo-cGMP rescue Blood High 18550847
2009 VWF A2 domain is mechanically unfolded by elongational forces in the physiological range (force proportional to multimer length squared, highest at the center of the multimer); only the unfolded A2 domain is cleaved by ADAMTS13, providing a homeostatic mechanism for size regulation by force-induced cleavage. Single-molecule force spectroscopy (optical tweezers), shear flow experiments, ADAMTS13 cleavage of unfolded A2 Science High 19498171
2009 Rab27a and its effector MyRIP anchor mature Weibel-Palade bodies to peripheral actin; depletion of Rab27a or MyRIP increases both basal and stimulated VWF secretion, but the released VWF is less multimerized and VWF strings under flow are shorter, indicating this complex controls peripheral WPB distribution and prevents release of incompletely processed VWF. siRNA depletion in primary endothelial cells, live imaging, WPB localization, VWF multimer analysis, flow-induced string assays Blood High 19270261
2010 VWF A1 domain unfolding from native to intermediate state (reduction of disulfide bond) increases GPIbα binding affinity ~20-fold; A1:GPIbα binding is thermodynamically coupled to A1 unfolding, and catch-to-slip bond transition under shear force is a manifestation of this coupling. Thermodynamic unfolding analysis, circular dichroism, GPIbα binding affinity measurements under reducing conditions Biophysical journal High 20713003
2010 VWF deficiency in endothelial cells (siRNA or VWD patient-derived progenitor cells) causes increased VEGFR-2-dependent proliferation and migration, decreased integrin αvβ3, and increased Ang-2 release, resulting in enhanced angiogenesis; VWF-deficient mice show increased vascularization in vivo. siRNA knockdown in HUVECs, EPC-derived cells from VWD patients, in vitro tube formation, mouse vascularization models Blood High 21048155
2010 Thrombospondin-1 (TSP1) competitively inhibits ADAMTS13 binding to VWF A2 and A3 domains, blocking ADAMTS13 cleavage by up to 70%; TSP1 also binds A1 domain, whereas ADAMTS13 interacts with all three A domains. ELISA binding assays with recombinant VWF A domains, western blot, residual collagen-binding assay for ADAMTS13 activity Thrombosis research Medium 20705333
2012 VWF propeptide (VWFpp) binds specifically to the D'D3 domain of mature VWF with high affinity under intracellular (pH 6.2, 10 mM Ca²⁺) conditions (KD = 0.2 nM) and weaker affinity under physiological plasma conditions (KD = 25–50 nM); this persistent binding in circulation attenuates VWF platelet adhesion by reducing GPIbα engagement. Surface plasmon resonance, novel anti-D'D3 mAbs, shear-induced platelet aggregation assays, flow chamber adhesion assays Blood High 22452980
2014 The kinetic interplay between two distinct GPIbα–VWF A1 contact surfaces regulates hemostasis and thrombosis: a mutation enhancing the minor site (I1309V) prolongs bond lifetime and produces type 2B VWD-like thrombocytopenia, while disrupting the major site (R1326H) shortens bond lifetime and produces hemostatic defects comparable to VWF deficiency; combining both mutations normalizes kinetics and function. VWF-A1 knock-in mice (I1309V, R1326H, double mutant), flow chamber assays, intravital microscopy, tail bleeding times Blood High 25293780
2016 A silent mutation (c.7464C>T) in VWF exon 44 causes intron 44 retention by inducing a stable hairpin structure 85 bp upstream of the 5' splice site that sequesters residues required for U1 snRNA interaction, resulting in a truncated VWF protein that accumulates in the endoplasmic reticulum. Patient transcript analysis, in vivo and ex vivo RT-PCR, confocal immunofluorescence of blood outgrowth endothelial cells, in silico pre-mRNA secondary/tertiary structure prediction Blood High 27543438
2016 HMGB1 upregulates VWF expression in vivo through a TLR2–MYD88–SP1 signaling pathway; TLR2 silencing abolishes MYD88 and VWF expression and SP1 phosphorylation, and glycyrrhizic acid or Tlr2 silencing blocks Sp1 binding to the Vwf promoter. Mouse acute hypoxia model, Tlr2 siRNA knockdown, TLR2-neutralizing antibody, SP1 inhibitor, chromatin immunoprecipitation (ChIP) of Sp1 at Vwf promoter European journal of immunology Medium 27480067
2017 GATA3 mediates upregulation of VWF transcription in lung adenocarcinoma-associated endothelial cells; conditioned medium from A549 cells increases GATA3 binding to a GATA binding motif at +220 of the VWF promoter, as confirmed by ChIP. Co-culture system with conditioned medium, ChIP assay for GATA3 at VWF promoter, siRNA knockdown of GATA3 vs ERG Oncotarget Medium 29299165
2018 Extracellular vimentin on the endothelial surface binds the VWF A2 domain to tether VWF strings; Vim-KO mouse cerebral arteries produce fewer VWF strings after histamine stimulation, and recombinant A2 protein or anti-vimentin antibodies block VWF string formation; A2 treatment improved cortical reperfusion after stroke in mice. Histamine stimulation of pressurized cerebral arteries, Vim-KO mice, anti-vimentin antibodies, recombinant A2 domain blockade, laser speckle contrast imaging Stroke High 30355099
2019 Extracellular PAD4 citrullinates ADAMTS13 on specific arginine residues, inhibiting its enzymatic activity; this leads to persistence of VWF-platelet strings in mesenteric venules and accelerates platelet plug formation after vessel injury; elevated ADAMTS13 citrullination was found in sepsis and elderly patients with comorbidities. In vivo r-huPAD4 injection intravital microscopy, mass spectrometry for citrullination sites, in vitro ADAMTS13 activity assays, ferric chloride injury model Circulation research High 31248335
2020 VWF maturation and release are controlled by two distinct regulators of Weibel-Palade body biogenesis: BLOC-2 (required for endosomal input during VWF maturation and WPB exocytosis) and the exocyst complex (which cooperates in WPB formation but clamps WPB release); WPBs from BLOC-2- or exocyst-depleted cells lack high-molecular-weight VWF forms. siRNA depletion of BLOC-2 and exocyst subunits, immunoprecipitation identifying BLOC-2–exocyst interaction, VWF multimer analysis of releasates, Endosidin2 pharmacological inhibition Blood High 32614949
2020 Platelets docking to endothelial VWF during inflammation secrete Angiopoietin-1 (Angpt1) that activates Tie-2 via the Cdc42-GEF FGD5 pathway, preventing vascular leaks during neutrophil extravasation; blocking VWF caused leaks during transmigration. Endothelial Tie-2 gene silencing and knockout, intravital microscopy of cremaster muscle, platelet-derived Angpt1 conditional KO, anti-VWF antibody blocking, fluorescent microsphere leakage assay Blood High 32369573
2021 Hyperadhesive VWF released during traumatic brain injury has its A1 domain constitutively exposed; selective blockade with recombinant VWF A2-domain protein reduced TBI-induced death by >50%, prevented TBI-induced platelet activation, microvesiculation, and hypercoagulable state, and protected endothelium from extracellular vesicle injury. Mouse lateral fluid percussion TBI model, A2 domain blockade (IP and IV), platelet activation assays, coagulation assays, mortality and neurological scoring Blood High 33507292
2021 Slc44a2/HNA-3a on neutrophils mediates adhesion to VWF at venous shear rates (100 s⁻¹) independently of β2 integrin; HNA-3b expression impairs this adhesion; Slc44a2-KO mice show massively reduced neutrophil recruitment in inflamed mesenteric venules after histamine-induced endothelial degranulation. Flow chamber adhesion assays with transfected HEK cells and donor-typed neutrophils, Slc44a2-KO mouse intravital microscopy Blood High 33556175
2022 VWF mediates vascular smooth muscle cell (VSMC) proliferation through its A2 domain binding to LRP4 receptor, which signals via αvβ3 integrin; LRP4 and αvβ3 co-localize by proximity ligation and co-immunoprecipitation; VWF-deficient mice show reduced hyperplasia in carotid ligation and femoral denudation models. siRNA against αv integrin and LRP4, RGT-peptide blocking, proximity ligation, co-IP, VWF-KO mouse arterial injury models, confocal microscopy Cardiovascular research High 33576766
2024 VWF A1 domain residues K1405–K1408 mediate binding to macrophage LRP1 (clusters II and IV); alanine mutagenesis of this cluster attenuates LRP1 binding and reduces VWF clearance in vivo; the aptamer BT200/rondaptivon pegol prolongs VWF half-life by blocking this interaction and also inhibiting macrophage galactose lectin and SR-AI scavenger receptor binding. LRP1 binding assays, alanine mutagenesis of K1405-K1408, in vivo clearance studies in mice, BT200 competition assays Blood High 38996211
2024 Endothelial PTP1B deletion promotes VWF exocytosis by increasing SNAP23 phosphorylation (through reduced PTP1B-mediated tyrosine dephosphorylation of SNAP23), leading to enhanced Weibel-Palade body membrane fusion, neutrophil adhesion, and venous thromboinflammation; NF-κB inhibition restored normal SNAP23 phosphorylation and VWF release. Inducible endothelial PTP1B-KO mice, inferior vena cava ligation, SNAP23 phosphorylation assays, co-IP of PTP1B with SNAP23, anti-VWF antibody blocking, intravital microscopy Circulation research High 38563147

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1998 Biochemistry and genetics of von Willebrand factor. Annual review of biochemistry 1108 9759493
1996 Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 963 8565074
2008 Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 787 18854154
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
1982 Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. The Journal of cell biology 657 6754744
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1983 Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor. Blood 489 6336654
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2002 Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science (New York, N.Y.) 467 12183630
1996 Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood 460 8874190
1986 Amino acid sequence of human von Willebrand factor. Biochemistry 451 3524673
1989 Structure of the gene for human von Willebrand factor. The Journal of biological chemistry 448 2584182
1986 Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 430 3087627
2000 Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood 421 10607717
1985 Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science (New York, N.Y.) 415 3874428
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2009 Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science (New York, N.Y.) 408 19498171
2010 Endothelial von Willebrand factor regulates angiogenesis. Blood 389 21048155
2003 Von Willebrand factor, platelets and endothelial cell interactions. Journal of thrombosis and haemostasis : JTH 344 12871266
1987 The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. The Journal of cell biology 335 3121636
2015 von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood 332 25712991
2011 New gene functions in megakaryopoiesis and platelet formation. Nature 332 22139419
2008 von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation 330 18347221
1990 Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. Proceedings of the National Academy of Sciences of the United States of America 315 2251280
2006 Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). Blood 314 16985174
2008 Hepatitis C virus infection protein network. Molecular systems biology 306 18985028
2010 Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 295 20231535
1985 Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proceedings of the National Academy of Sciences of the United States of America 284 2864688
2007 The role of von Willebrand factor in thrombus formation. Thrombosis research 268 17493665
1986 Full-length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein considerably larger than the mature vWF subunit. The EMBO journal 241 3019665
2006 Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo. Blood 122 16788103
1987 Expression of variant von Willebrand factor (vWF) cDNA in heterologous cells: requirement of the pro-polypeptide in vWF multimer formation. The EMBO journal 115 3500851
2001 Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen. Thrombosis and haemostasis 105 11583318
2005 A critical role for 14-3-3zeta protein in regulating the VWF binding function of platelet glycoprotein Ib-IX and its therapeutic implications. Blood 103 15941906
2017 ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery. Blood 94 28428179
2009 Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells. Blood 87 19270261
2013 The comparative effects of valsartan and amlodipine on vWf levels and N/L ratio in patients with newly diagnosed hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993) 86 23289969
2005 Platelet-derived VWF-cleaving metalloprotease ADAMTS-13. Journal of thrombosis and haemostasis : JTH 86 16176307
2008 Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway. Blood 84 18550847
2019 Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis After Vessel Injury. Circulation research 83 31248335
2007 N-linked glycosylation of VWF modulates its interaction with ADAMTS13. Blood 81 17975018
2021 Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis. Seminars in thrombosis and hemostasis 80 33893632
2012 ADAMTS13 reduces VWF-mediated acute inflammation following focal cerebral ischemia in mice. Journal of thrombosis and haemostasis : JTH 79 22712744
2015 Role of fluid shear stress in regulating VWF structure, function and related blood disorders. Biorheology 77 26600266
1995 Identification of two mutations (Arg611Cys and Arg611His) in the A1 loop of von Willebrand factor (vWF) responsible for type 2 von Willebrand disease with decreased platelet-dependent function of vWF. Blood 68 7620154
2003 Collagen-binding mode of vWF-A3 domain determined by a transferred cross-saturation experiment. Nature structural biology 66 12447349
2005 Botrocetin/VWF-induced signaling through GPIb-IX-V produces TxA2 in an alphaIIbbeta3- and aggregation-independent manner. Blood 65 15985541
2021 ADAMTS13 regulation of VWF multimer distribution in severe COVID-19. Journal of thrombosis and haemostasis : JTH 60 34053187
2016 Levels of Serum 25(OH)VD3, HIF-1α, VEGF, vWf, and IGF-1 and Their Correlation in Type 2 Diabetes Patients with Different Urine Albumin Creatinine Ratio. Journal of diabetes research 59 27069929
2011 Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels. BMC medical genetics 56 21810271
2002 The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF. Blood 56 12176890
2022 Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction. Journal of thrombosis and haemostasis : JTH 54 35875995
2004 Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells. Blood 51 15331450
1998 von Willebrand factor (vWf) as a plasma marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:AgII). Thrombosis and haemostasis 50 9869174
1999 Role of activation of the coagulation factor VIII in interaction with vWf, phospholipid, and functioning within the factor Xase complex. Trends in cardiovascular medicine 49 10881749
2013 Increased VWF antigen levels and decreased ADAMTS13 activity in preeclampsia. Hematology (Amsterdam, Netherlands) 48 23433535
1986 Application of an enzyme-linked immunosorbent assay (ELISA) to von Willebrand factor (vWF) and its derivatives. Thrombosis research 48 2425450
2020 Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2. Blood 47 32369573
2003 Expression of human factor VIII under control of the platelet-specific alphaIIb promoter in megakaryocytic cell line as well as storage together with VWF. Molecular genetics and metabolism 46 12765843
1993 Pretreatment plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand factor (vWF) in patients with operable cervical cancer: influence of surgical-pathological stage, tumor size, histologic type, and lymph node status. Gynecologic oncology 44 8314538
2016 Regulation of VWF expression, and secretion in health and disease. Current opinion in hematology 42 26771163
2004 The roles of ADP and TXA in botrocetin/VWF-induced aggregation of washed platelets. Journal of thrombosis and haemostasis : JTH 42 15613029
2010 Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro. Thrombosis research 39 20705333
2019 The ADAMTS13-VWF axis is dysregulated in chronic thromboembolic pulmonary hypertension. The European respiratory journal 38 30655285
2006 Regulated release of VWF and FVIII and the biologic implications. Pediatric blood & cancer 38 16470522
2022 The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies. Journal of thrombosis and haemostasis : JTH 37 35644028
2018 Extracellular Vimentin/VWF (von Willebrand Factor) Interaction Contributes to VWF String Formation and Stroke Pathology. Stroke 35 30355099
2013 Correlation between endogenous VWF:Ag and PK parameters and bleeding frequency in severe haemophilia A subjects during three-times-weekly prophylaxis with rFVIII-FS. Haemophilia : the official journal of the World Federation of Hemophilia 35 24252058
2010 The mechanism of VWF-mediated platelet GPIbalpha binding. Biophysical journal 35 20713003
2021 Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice. Blood 33 33507292
2016 Intron retention resulting from a silent mutation in the VWF gene that structurally influences the 5' splice site. Blood 33 27543438
2014 Misfolding of vWF to pathologically disordered conformations impacts the severity of von Willebrand disease. Biophysical journal 33 25185554
2021 Von Willebrand factor collagen-binding capacity predicts in-hospital mortality in COVID-19 patients: insight from VWF/ADAMTS13 ratio imbalance. Angiogenesis 32 33974165
2007 A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3. Journal of thrombosis and haemostasis : JTH 32 17371490
2021 Impaired adhesion of neutrophils expressing Slc44a2/HNA-3b to VWF protects against NETosis under venous shear rates. Blood 30 33556175
2022 COVID-19 microthrombosis: unusually large VWF multimers are a platform for activation of the alternative complement pathway under cytokine storm. International journal of hematology 29 35316498
2022 Microlyse: a thrombolytic agent that targets VWF for clearance of microvascular thrombosis. Blood 28 34752601
2016 Vps33b regulates Vwf-positive vesicular trafficking in megakaryocytes. The Journal of pathology 28 27319744
2012 von Willebrand factor (VWF) propeptide binding to VWF D'D3 domain attenuates platelet activation and adhesion. Blood 28 22452980
2023 Small Extracellular Vesicle-Derived vWF Induces a Positive Feedback Loop between Tumor and Endothelial Cells to Promote Angiogenesis and Metastasis in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 27 37387563
2021 Plasma and rhADAMTS13 reduce trauma-induced organ failure by restoring the ADAMTS13-VWF axis. Blood advances 26 34505883
2017 Resveratrol attenuates hydrogen peroxide‑induced apoptosis, reactive oxygen species generation, and PSGL‑1 and VWF activation in human umbilical vein endothelial cells, potentially via MAPK signalling pathways. Molecular medicine reports 26 29207192
2001 Crotalin, a vWF and GP Ib cleaving metalloproteinase from venom of Crotalus atrox. Thrombosis and haemostasis 26 11776320
2022 The VWF/LRP4/αVβ3-axis represents a novel pathway regulating proliferation of human vascular smooth muscle cells. Cardiovascular research 25 33576766
2020 Low VWF levels in children and lack of association with bleeding in children undergoing tonsillectomy. Blood advances 25 31905240
2003 Deletion of alanine 2201 in the FVIII C2 domain results in mild hemophilia A by impairing FVIII binding to VWF and phospholipids and destroys a major FVIII antigenic determinant involved in inhibitor development. Blood 24 12969981
2020 VWF maturation and release are controlled by 2 regulators of Weibel-Palade body biogenesis: exocyst and BLOC-2. Blood 23 32614949
2020 Emerging mechanisms to modulate VWF release from endothelial cells. The international journal of biochemistry & cell biology 23 33301925
2017 GATA3-induced vWF upregulation in the lung adenocarcinoma vasculature. Oncotarget 23 29299165
2022 The GPIbα intracellular tail - role in transducing VWF- and collagen/GPVI-mediated signaling. Haematologica 22 34134470
2022 Hyperglycemia-induced oxidative stress promotes tumor metastasis by upregulating vWF expression in endothelial cells through the transcription factor GATA1. Oncogene 21 35094008
2018 A factor VIII-nanobody fusion protein forming an ultrastable complex with VWF: effect on clearance and antibody formation. Blood 21 30064978
2016 HMGB1 facilitates hypoxia-induced vWF upregulation through TLR2-MYD88-SP1 pathway. European journal of immunology 20 27480067
2017 Laboratory Testing for von Willebrand Factor Collagen Binding (VWF:CB). Methods in molecular biology (Clifton, N.J.) 19 28804845
2017 Laboratory Testing for von Willebrand Factor Ristocetin Cofactor (VWF:RCo). Methods in molecular biology (Clifton, N.J.) 19 28804846
2015 FcRn Rescues Recombinant Factor VIII Fc Fusion Protein from a VWF Independent FVIII Clearance Pathway in Mouse Hepatocytes. PloS one 19 25905473
2012 Immunoexpression of RANK, RANKL, OPG, VEGF, and vWF in radicular and dentigerous cysts. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 19 23278112
2022 Endothelial VWF is critical for the pathogenesis of vaso-occlusive episode in a mouse model of sickle cell disease. Proceedings of the National Academy of Sciences of the United States of America 18 35969769
2021 von Willebrand factor antigen levels are associated with burden of rare nonsynonymous variants in the VWF gene. Blood 18 33556167
2021 Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis. Frontiers in oncology 18 33968738
2020 ADAMTS13 activity, high VWF and FVIII levels in the pathogenesis of deep vein thrombosis. Thrombosis research 18 33212380
2019 Hemophilia A and B mice, but not VWF-/-mice, display bone defects in congenital development and remodeling after injury. Scientific reports 18 31594977
2018 Molecular Imaging of VWF (von Willebrand Factor) and Platelet Adhesion in Postischemic Impaired Microvascular Reflow. Circulation. Cardiovascular imaging 18 30571316
2017 Laboratory Testing for von Willebrand Factor Antigen (VWF:Ag). Methods in molecular biology (Clifton, N.J.) 18 28804844
2023 New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF. Frontiers in immunology 17 36926331
2019 In Vitro Measurement and Modeling of Platelet Adhesion on VWF-Coated Surfaces in Channel Flow. Biophysical journal 17 30824114
2012 PR3 and elastase alter PAR1 signaling and trigger vWF release via a calcium-independent mechanism from glomerular endothelial cells. PloS one 17 22952809
1996 Levels of von Willebrand factor, insulin resistance syndrome, and a common vWF gene polymorphism in non-insulin-dependent (type 2) diabetes mellitus. Diabetic medicine : a journal of the British Diabetic Association 17 8862946
2024 The aptamer BT200 blocks interaction of K1405-K1408 in the VWF-A1 domain with macrophage LRP1. Blood 16 38996211
2020 Association between ADAMTS13 activity-VWF antigen imbalance and the therapeutic effect of HAIC in patients with hepatocellular carcinoma. World journal of gastroenterology 16 33362379
2018 Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA. Haematologica 16 30361419
2020 Factor VIII pharmacokinetics associates with genetic modifiers of VWF and FVIII clearance in an adult hemophilia A population. Journal of thrombosis and haemostasis : JTH 15 33219619
2008 The role of VWF in the immunogenicity of FVIII. Thrombosis research 15 18549909
2022 rhADAMTS13 reduces oxidative stress by cleaving VWF in ischaemia/reperfusion-induced acute kidney injury. Acta physiologica (Oxford, England) 14 34989474
2022 Single-cell transcriptional analysis of human endothelial colony-forming cells from patients with low VWF levels. Blood 14 35143643
2018 Coupling of a specific photoreactive triple-helical peptide to crosslinked collagen films restores binding and activation of DDR2 and VWF. Biomaterials 14 30099278
2017 A novel function of vitellogenin subdomain, vWF type D, as a toxin-binding protein in the pufferfish Takifugu pardalis ovary. Toxicon : official journal of the International Society on Toxinology 14 28651990
2016 Mutations in the D'D3 region of VWF traditionally associated with type 1 VWD lead to quantitative and qualitative deficiencies of VWF. Thrombosis research 14 27533707
2006 [Plasma levels of vWF and NO in patients with metabolic syndrome and their relationship with metabolic disorders]. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 14 16764036
2006 Molecular mapping of the chloride-binding site in von Willebrand factor (VWF): energetics and conformational effects on the VWF/ADAMTS-13 interaction. The Journal of biological chemistry 14 16899464
1995 Induction of GPIb/IX-vWF receptor-ligand translocation on surface-activated platelets. Arteriosclerosis, thrombosis, and vascular biology 14 7749877
2020 von Willebrand factor promotes platelet-induced metastasis of osteosarcoma through activation of the VWF-GPIb axis. Journal of bone oncology 12 33101888
2017 Identification of extant vertebrate Myxine glutinosa VWF: evolutionary conservation of primary hemostasis. Blood 12 28899852
2014 Exploiting the kinetic interplay between GPIbα-VWF binding interfaces to regulate hemostasis and thrombosis. Blood 12 25293780
2024 Endothelial PTP1B Deletion Promotes VWF Exocytosis and Venous Thromboinflammation. Circulation research 11 38563147
2022 Multifaceted pathomolecular mechanism of a VWF large deletion involved in the pathogenesis of severe VWD. Blood advances 11 34861678
2020 Association of von Willebrand factor (vWF) expression with lymph node metastasis and hemodynamics in papillary thyroid carcinoma. European review for medical and pharmacological sciences 11 32196607
2001 Increased glomerular Vwf after kidney irradiation is not due to increased biosynthesis or endothelial cell proliferation. Radiation research 11 11418069