Evidence map›Paper›PMID 21670495›Full record

ArticleThe Journal of clinical investigation2011

P2X7 receptor signaling contributes to tissue factor-dependent thrombosis in mice.

Christian Furlan-Freguia, Patrizia Marchese, András Gruber, Zaverio M Ruggeri, Wolfram Ruf

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% 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

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. P2XScience advances · 2024
    Article
  13. Review
  14. The Effect of Extracellular Vesicles on Thrombosis.Journal of cardiovascular translational research · 2023
    Review
  15. Article
  16. Animal Models for the Investigation of P2X7 Receptors.International journal of molecular sciences · 2023
    Review
  17. Review
  18. Article
  19. Triazoles with inhibitory action on P2X7R impaired the acute inflammatory response in vivo and modulated the hemostatic balance in vitro and ex vivo.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  20. Review

33 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Christian Furlan-FreguiaDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
Patrizia Marchese
András Gruber
Zaverio M Ruggeri
Wolfram Ruf
Scripps Research Institute · US

Funding

THROMBUS FORMATION IN BABOONSP01HL031950 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H · 1985 to 2015
$29.4M
STRUCTURE &FUNCTION OF PLATELET MEMBRANE GLYCOPROTEINSR01HL042846 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUGGERI, ZAVERIO M · 1989 to 2014
$2.4M
NHLBI NIH HHS HL-31950NHLBI NIH HHS P01 HL031950NHLBI NIH HHS R01 HL042846
6 · The paper itself

Abstract

Thrombosis is initiated by tissue factor (TF), a coagulation cofactor/receptor expressed in the vessel wall, on myeloid cells, and on microparticles (MPs) with variable procoagulant activity. However, the molecular pathways that generate prothrombotic TF in vivo are poorly defined. The oxidoreductase protein disulfide isomerase (PDI) is thought to be involved in the activation of TF. Here, we found that in mouse myeloid cells, ATP-triggered signaling through purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7 receptor; encoded by P2rx7) induced activation (decryption) of TF procoagulant activity and promoted release of TF+ MPs from macrophages and SMCs. The generation of prothrombotic MPs required P2X7 receptor-dependent production of ROS leading to increased availability of solvent-accessible extracellular thiols. An antibody to PDI with antithrombotic activity in vivo attenuated the release of procoagulant MPs. In addition, P2rx7-/- mice were protected from TF-dependent FeCl3-induced carotid artery thrombosis. BM chimeras revealed that P2X7 receptor prothrombotic function was present in both hematopoietic and vessel wall compartments. In contrast, an alternative anti-PDI antibody showed activities consistent with cellular activation typically induced by P2X7 receptor signaling. This anti-PDI antibody restored TF-dependent thrombosis in P2rx7-/- mice. These data suggest that PDI regulates a critical P2X7 receptor-dependent signaling pathway that generates prothrombotic TF, defining a link between inflammation and thrombosis with potential implications for antithrombotic therapy.

Indexed as

Adenosine TriphosphateAnimalsBone Marrow TransplantationCell-Derived MicroparticlesEnzyme InhibitorsInflammationMacrophagesMiceMice, Inbred C57BLMice, KnockoutMyeloid CellsNADPH OxidasesProtein Disulfide-IsomerasesReceptors, Purinergic P2X7Signal TransductionThromboplastinAdenosine TriphosphateEnzyme InhibitorsNADPH OxidasesProtein Disulfide-IsomerasesReceptors, Purinergic P2X7Thromboplastin

Identifiers

PMID21670495
PMCPMC3127437
OpenAlexW2170640128

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.