Evidence map›Paper›PMID 29793936›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction.

Miruna Popa, Sibgha Tahir, Julia Elrod, Su Hwan Kim, Florian Leuschner, Thorsten Kessler, Peter Bugert, Ulrich Pohl, Andreas H Wagner, Markus Hecker

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  5. Acta pharmaceutica Sinica. B · 2024
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  19. The CD40-CD40L Dyad as Immunotherapeutic Target in Cardiovascular Disease.Journal of cardiovascular translational research · 2021
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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

10 authors at 4 institutions in 1 country.

Miruna PopaDepartment of Cardiovascular Physiology, Heidelberg University, 69120 Heidelberg, Germany.
Sibgha TahirDepartment of Cardiovascular Physiology, Heidelberg University, 69120 Heidelberg, Germany.
Julia ElrodDepartment of Cardiovascular Physiology, Heidelberg University, 69120 Heidelberg, Germany.
Su Hwan KimDepartment of Cardiovascular Physiology, Heidelberg University, 69120 Heidelberg, Germany.
Florian LeuschnerInternal Medicine III, University Clinics Heidelberg, 69120 Heidelberg, Germany.
Thorsten KesslerDepartment of Cardiovascular Diseases, German Heart Centre Munich, Technical University Munich, 80636 Munich, Germany.
Peter BugertGerman Red Cross Blood Service Baden-Württemberg-Hessen, Institute of Transfusion Medicine and Immunology, 68167 Mannheim, Germany.
Ulrich PohlWalter Brendel Centre of Experimental Medicine, Biomedical Center of Ludwig Maximilian University of Munich (LMU), Ludwig Maximilian University of Munich, 82152 Munich Germany.
Andreas H WagnerDepartment of Cardiovascular Physiology, Heidelberg University, 69120 Heidelberg, Germany; a.wagner@physiologie.uni-heidelberg.de.ORCID 0000-0003-2723-5953
Markus HeckerDepartment of Cardiovascular Physiology, Heidelberg University, 69120 Heidelberg, Germany.
Heidelberg University · DEDeutsches Herzzentrum München · DEGerman Centre for Cardiovascular Research · DEGerman Red Cross · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Monocyte extravasation into the vessel wall is a key step in atherogenesis. It is still elusive how monocytes transmigrate through the endothelial cell (EC) monolayer at atherosclerosis predilection sites. Platelets tethered to ultra-large von Willebrand factor (ULVWF) multimers deposited on the luminal EC surface following CD40 ligand (CD154) stimulation may facilitate monocyte diapedesis. Human ECs grown in a parallel plate flow chamber for live-cell imaging or Transwell permeable supports for transmigration assay were exposed to fluid or orbital shear stress and CD154. Human isolated platelets and/or monocytes were superfused over or added on top of the EC monolayer. Plasma levels and activity of the ULVWF multimer-cleaving protease ADAMTS13 were compared between coronary artery disease (CAD) patients and controls and were verified by the bioassay. Two-photon intravital microscopy was performed to monitor CD154-dependent leukocyte recruitment in the cremaster microcirculation of ADAMTS13-deficient versus wild-type mice. CD154-induced ULVWF multimer-platelet string formation on the EC surface trapped monocytes and facilitated transmigration through the EC monolayer despite high shear stress. Two-photon intravital microscopy revealed CD154-induced ULVWF multimer-platelet string formation preferentially in venules, due to strong EC expression of CD40, causing prominent downstream leukocyte extravasation. Plasma ADAMTS13 abundance and activity were significantly reduced in CAD patients and strongly facilitated both ULVWF multimer-platelet string formation and monocyte trapping in vitro. Moderate ADAMTS13 deficiency in CAD patients augments CD154-mediated deposition of platelet-decorated ULVWF multimers on the luminal EC surface, reinforcing the trapping of circulating monocytes at atherosclerosis predilection sites and promoting their diapedesis.

Indexed as

ADAMTS13 ProteinAdolescentAdultAgedAnimalsAtherosclerosisBlood PlateletsCD40 AntigensCell CommunicationCells, CulturedEndothelial CellsEndothelium, VascularHumansHuman Umbilical Vein Endothelial CellsMiceMice, Inbred C57BLADAMTS13 ProteinCD40 Antigensvon Willebrand FactorADAMTS13CD40coronary artery diseaseendothelial cellsvon Willebrand factor

Identifiers

PMID29793936
PMCPMC6004483
OpenAlexW2804799628

What OpenQuestion holds

Textmetadata
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.