Evidence map›Paper›PMID 32544272›Full record

ArticleJournal of thrombosis and haemostasis : JTH2020

Factor VIII binding affects the mechanical unraveling of the A2 domain of von Willebrand factor.

Wenpeng Cao, Wenjing Cao, Wei Zhang, X Long Zheng, X Frank Zhang

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

8 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.Journal of thrombosis and haemostasis : JTH · 2023
    Article
  8. 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

5 authors at 2 institutions in 1 country.

Wenpeng CaoDepartment of Bioengineering, Lehigh University, Bethlehem, PA, USA.
Wenjing CaoDepartment of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, USA.
Wei ZhangDepartment of Bioengineering, Lehigh University, Bethlehem, PA, USA.
X Long ZhengDepartment of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0003-1680-5295
X Frank ZhangDepartment of Bioengineering, Lehigh University, Bethlehem, PA, USA.
Lehigh University · USUniversity of Kansas Medical Center · US

Funding

Mechanical regulation of von Willebrand factorR01HL153986 · NHLBI · UNIVERSITY OF MASSACHUSETTS AMHERST · PI ZHANG, XIAOHUI · 2021 to 2024
$2.2M
Pathogenesis of thrombotic microangiopathiesR01HL164016 · NHLBI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI X. Long Zheng · 2023 to 2026
$2.1M
Pathogenesis of Thrombotic MicroangiopathyR01HL126724 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ZHENG, X. LONG · 2015 to 2018
$1.8M
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic PurpuraR01HL144552 · NHLBI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ZHENG, X. LONG · 2019 to 2022
$1.8M
Mechanism underlying cofactor-dependent proteolysis of von Willebrand FactorR01HL157975 · NHLBI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ZHANG, XIAOHUI FRANK, ZHENG, X. LONG · 2022 to 2025
$1.8M
Single-cell analysis of endothelial mechanotransduction mediated by endothelial surface glycocalyxR21HL152348 · NHLBI · UNIVERSITY OF MASSACHUSETTS AMHERST · PI ZHANG, XIAOHUI · 2020 to 2021
$408k
NHLBI NIH HHS R01 HL126724NHLBI NIH HHS R01 HL144552NHLBI NIH HHS R01 HL153986NHLBI NIH HHS R01 HL157975NHLBI NIH HHS R01 HL164016NHLBI NIH HHS R21 HL152348
6 · The paper itself

Abstract

backgroundProteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 is crucial for normal hemostasis. Our previous studies demonstrate that binding of coagulation factor VIII (or FVIII) to VWF enhances the proteolytic cleavage of VWF by ADAMTS13 under shear.

objectivesPresent study aims to determine the mechanism underlying FVIII-mediated enhancing effect on VWF proteolysis by ADAMTS13 under force.

methodsSingle molecular force spectroscopy, atomic force microscopy, and surface plasmon resonance are all used.

resultsUsing single molecule force spectroscopy, we show that an addition of FVIII (~5 nmol/L) to D'D3 or D'D3A1 does not significantly alter force-induced unfolding of these fragments; however, an addition of FVIII at the same concentration to D'D3A1A2 eliminates its long unfolding event at ~40 nm, suggesting that binding of FVIII to D'D3 and/or A2 may result in force-induced conformational changes in A2 domain. Atomic force spectroscopy further demonstrates the direct binding between FVIII and D'D3 (or A2) with an intrinsic 2-dimensional off-rate (k

conclusionsOur results suggest that binding of FVIII to D'D3 and/or A2 may alter the mechanical property in the central A2 domain. The findings provide novel insight into the molecular mechanism underlying FVIII-dependent regulation of VWF proteolysis by ADAMTS13 under mechanical force.

Indexed as

Hemostaticsvon Willebrand FactorFactor VIIIHumansProteolysisFactor VIIIHemostaticsvon Willebrand FactorADAMTS13and mechanical forceFactor VIIIhemostasisvon Willebrand factor

Identifiers

PMID32544272
PMCPMC7789802
OpenAlexW3035079049

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.