Evidence map›Paper›PMID 25824964›Full record

ArticleBritish journal of pharmacology2015

Aspirin-induced histone acetylation in endothelial cells enhances synthesis of the secreted isoform of netrin-1 thus inhibiting monocyte vascular infiltration.

Gabriella Passacquale, Alkystis Phinikaridou, Christina Warboys, Margaret Cooper, Begona Lavin, Alessio Alfieri, Marcelo E Andia, Rene M Botnar, Albert Ferro

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 43 citations in OpenAlex.

  1. Trial
  2. Article
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  5. Review
  6. Is netrin-1 a reliable inflammatory marker for periodontitis?Journal of advanced periodontology & implant dentistry · 2022
    Article
  7. Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation.International journal of molecular sciences · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. The Role of Histone Protein Acetylation in Regulating Endothelial Function.Frontiers in cell and developmental biology · 2021
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Article
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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

9 authors at 2 institutions in 1 country.

Gabriella PassacqualeDepartment of Clinical Pharmacology, BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK.
Alkystis PhinikaridouDivision of Imaging Sciences and Biomedical Engineering, BHF Centre of Research Excellence and the Wellcome Trust/EPSRC Medical Engineering Centre, King's College London, London, UK.
Christina WarboysDepartment of Clinical Pharmacology, BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK.
Margaret CooperDivision of Imaging Sciences and Biomedical Engineering, BHF Centre of Research Excellence and the Wellcome Trust/EPSRC Medical Engineering Centre, King's College London, London, UK.
Begona LavinDivision of Imaging Sciences and Biomedical Engineering, BHF Centre of Research Excellence and the Wellcome Trust/EPSRC Medical Engineering Centre, King's College London, London, UK.
Alessio AlfieriDepartment of Vascular Biology, BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK.
Marcelo E AndiaDivision of Imaging Sciences and Biomedical Engineering, BHF Centre of Research Excellence and the Wellcome Trust/EPSRC Medical Engineering Centre, King's College London, London, UK.
Rene M BotnarDivision of Imaging Sciences and Biomedical Engineering, BHF Centre of Research Excellence and the Wellcome Trust/EPSRC Medical Engineering Centre, King's College London, London, UK.
Albert FerroDepartment of Clinical Pharmacology, BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK.
King's College London · GBWellcome EPSRC Centre for Medical Engineering · GB

Funding

British Heart Foundation PG/12/16/29443British Heart Foundation RG/12/1/29262
6 · The paper itself

Abstract

background and purposeThere are conflicting data regarding whether netrin-1 retards or accelerates atherosclerosis progression, as it can lead either to monocyte repulsion from or retention within plaques depending on its cellular source. We investigated the effect of aspirin, which is widely used in cardiovascular prophylaxis, on the synthesis of different isoforms of netrin-1 by endothelial cells under pro-inflammatory conditions, and defined the net effect of aspirin-dependent systemic modulation of netrin-1 on atherosclerosis progression. EXPERIMENTAL APPROACH: Netrin-1 synthesis was studied in vitro using human endothelial cells stimulated with TNF-α, with or without aspirin treatment. In vivo experiments were conducted in ApoE(-/-) mice fed with a high-fat diet (HFD), receiving either aspirin or clopidogrel. KEY

resultsTNF-α-induced NF-κB activation up-regulated the nuclear isoform of netrin-1, while simultaneously reducing secreted netrin-1. Down-regulation of the secreted isoform compromised the chemorepellent action of the endothelium against monocyte chemotaxis. Aspirin counteracted TNF-α-mediated effects on netrin-1 synthesis by endothelial cells through COX-dependent inhibition of NF-κB and concomitant histone hyperacetylation. Administration of aspirin to ApoE(-/-) mice on HFD increased blood and arterial wall levels of netrin-1 independently of its effects on platelets, accompanied by reduced plaque size and content of monocytes/macrophages, compared with untreated or clopidogrel-treated mice. In vivo blockade of netrin-1 enhanced monocyte plaque infiltration in aspirin-treated ApoE(-/-) mice. CONCLUSIONS AND IMPLICATIONS: Aspirin counteracts down-regulation of secreted netrin-1 induced by pro-inflammatory stimuli in endothelial cells. The aspirin-dependent increase of netrin-1 in ApoE(-/-) mice exerts anti-atherogenic effects by preventing arterial accumulation of monocytes.

Indexed as

AcetylationAnimalsApolipoproteins EAspirinHistonesHumansHuman Umbilical Vein Endothelial CellsMaleMiceMice, KnockoutMonocytesNerve Growth FactorsNetrin-1Protein IsoformsTumor Necrosis Factor-alphaTumor Suppressor ProteinsApolipoproteins EAspirinHistonesNerve Growth FactorsNetrin-1NTN1 protein, humanNtn1 protein, mouseProtein IsoformsTumor Necrosis Factor-alphaTumor Suppressor Proteins

Identifiers

PMID25824964
PMCPMC4507159
OpenAlexW2063028221

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.