Evidence map›Paper›PMID 35343037›Full record

ArticleJournal of thrombosis and haemostasis : JTH2022

Endothelial-derived von Willebrand factor accelerates fibrin clotting within engineered microvessels.

Samuel G Rayner, Zackary Scholl, Christian J Mandrycky, Junmei Chen, Karina N LaValley, Peter J Leary, William A Altemeier, W Conrad Liles, Dominic W Chung, José A López and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Hemodynamic simulation andPhysics of fluids (Woodbury, N.Y. : 1994) · 2025
    Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Samuel G RaynerDepartment of Medicine, University of Washington, Seattle, Washington, USA.ORCID 0000-0002-2541-4221
Zackary SchollDepartment of Bioengineering, University of Washington, Seattle, Washington, USA.
Christian J MandryckyDepartment of Bioengineering, University of Washington, Seattle, Washington, USA.
Junmei ChenBloodworks Research Institute, Seattle, Washington, USA.
Karina N LaValleyDepartment of Bioengineering, University of Washington, Seattle, Washington, USA.
Peter J LearyDepartment of Medicine, University of Washington, Seattle, Washington, USA.
William A AltemeierDepartment of Medicine, University of Washington, Seattle, Washington, USA.
W Conrad LilesDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Dominic W ChungBloodworks Research Institute, Seattle, Washington, USA.
José A LópezDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Hongxia FuDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Ying ZhengDepartment of Bioengineering, University of Washington, Seattle, Washington, USA.ORCID 0000-0003-2723-9022
University of Washington · USCalifornia Institute for Regenerative Medicine · USBloodworks Northwest · US

Funding

NCCIH Supplement to NCATS/CTSA Program for KL2 Scholars - M. SoddersKL2TR002317 · NCATS · UNIVERSITY OF WASHINGTON · PI Christy Michelle McKinney · 2017 to 2026
$14.5M
RESEARCH TRAINING IN HEMATOLOGYT32HL007093 · NHLBI · UNIVERSITY OF WASHINGTON · PI Janis L Abkowitz · 1985 to 2026
$13.9M
Molecular and Translational Studies in Hematologic DisordersR35HL145262 · NHLBI · BLOODWORKS · PI LOPEZ, JOSE ARON · 2019 to 2024
$6.5M
Molecular Mechanisms in Pediatric Cerebral Malaria Pathogenesis and ImmunityR01AI141602 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI SEYDEL, KARL BOYNTON, SMITH, JOSEPH D · 2019 to 2022
$2.9M
3D Models of the Blood-Brain Barrier for Studying Trauma-Induced Cerebral and Systemic InjuriesR33HL154250 · NHLBI · UNIVERSITY OF WASHINGTON · PI DONG, JING-FEI, ZHENG, YING · 2022 to 2024
$2.7M
3D Models of the Blood-Brain Barrier for Studying Trauma-Induced Cerebral and Systemic InjuriesR61HL154250 · NHLBI · UNIVERSITY OF WASHINGTON · PI DONG, JING-FEI, ZHENG, YING · 2020 to 2021
$1.6M
Mechanoregulatory mechanisms of von Willebrand disease and thrombosisK25HL135432 · NHLBI · UNIVERSITY OF WASHINGTON · PI FU, HONGXIA · 2017 to 2021
$890k
Modeling Von Willebrand Factor Behavior in the Pulmonary Circulation in Health and DiseaseF32HL143949 · NHLBI · UNIVERSITY OF WASHINGTON · PI RAYNER, SAMUEL GIBSON · 2018 to 2019
$112k
NCATS NIH HHS KL2 TR002317NHLBI NIH HHS F32 HL143949NHLBI NIH HHS K25 HL135432NHLBI NIH HHS R33 HL154250NHLBI NIH HHS R35 HL145262NHLBI NIH HHS R61 HL154250NHLBI NIH HHS T32 HL007093NIAID NIH HHS R01 AI141602NIH HHS 5KL2TR002317-04NIH HHS 5T32HL007093-44NIH HHS HL143949NIH HHS R01AI141602NIH HHS R35HL145262NIH HHS R61HL154250NIH HHS T32675551
6 · The paper itself

Abstract

backgroundVon Willebrand factor (VWF) is classically associated with primary hemostasis and platelet-rich arterial thromboses, but recently has also been implicated in fibrin clotting and venous thrombosis. Direct interaction between fibrin and VWF may mediate these processes, although prior reports are conflicting.

objectivesWe combined two complementary platforms to characterize VWF-fibrin(ogen) interactions and identify their potential physiologic significance.

methodsEngineered microvessels were lined with human endothelial cells, cultured under flow, and activated to release VWF and form transluminal VWF fibers. Fibrinogen, fibrin monomers, or polymerizing fibrin were then perfused, and interactions with VWF evaluated. Thrombin and fibrinogen were perfused into living versus paraformeldahyde-fixed microvessels and the pressure drop across microvessels monitored. Separately, protein binding to tethered VWF was assessed on a single-molecule level using total internal reflection fluorescence (TIRF) microscopy.

resultsWithin microvessels, VWF fibers colocalized with polymerizing fibrin, but not fibrinogen. TIRF microscopy showed no colocalization between VWF and fibrinogen or fibrin monomers in a microfluidic flow chamber across a range of shear rates and protein concentrations. Thrombin-mediated fibrin polymerization within living microvessels triggered endothelial VWF release, increasing the rate and amount of microvessel obstruction compared to fixed vessels with an inert endothelium.

conclusionsWe did not identify specific binding between fibrin(ogen) and VWF at a single-molecule level. Despite this, our results suggest that rapid release of endothelial VWF during clotting may provide a physical support for fibrin polymerization and accelerate thrombosis. This interaction may be of fundamental importance for the understanding and treatment of human thrombotic disease.

Indexed as

Thrombosisvon Willebrand FactorEndothelial CellsEndotheliumFibrinFibrinogenHumansMicrovesselsThrombinFibrinFibrinogenThrombinvon Willebrand Factorbioengineeringfibrinprotein bindingthrombosisvon Willebrand factor

Identifiers

PMID35343037
PMCPMC10581744
OpenAlexW4220846833

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.