Evidence map›Paper›PMID 27154726›Full record

ArticleCirculation2016

Formyl-Peptide Receptor 2/3/Lipoxin A4 Receptor Regulates Neutrophil-Platelet Aggregation and Attenuates Cerebral Inflammation: Impact for Therapy in Cardiovascular Disease.

Shantel A Vital, Felix Becker, Paul M Holloway, Janice Russell, Mauro Perretti, D Neil Granger, Felicity N E Gavins

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

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
9.6field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Thromborepair: the tissue repair partner to thromboinflammation.Blood vessels, thrombosis & hemostasis · 2026
    Review
  4. Article
  5. Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025
    Review
  6. Annexin A1: The dawn of ischemic stroke (Review).Molecular medicine reports · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Lipoxins AJournal of neuroinflammation · 2024
    Article
  16. Spatio-Temporal Characterization of Brain Inflammation in a Non-human Primate Stroke Model Mimicking Endovascular Thrombectomy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  17. Article
  18. Annexin A1 (Ac2-26)-dependent Fpr2 receptor alleviates sepsis-induced acute kidney injury by inhibiting inflammation and apoptosis in vivo and in vitro.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Shantel A VitalFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.).
Felix BeckerFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.).
Paul M HollowayFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.).
Janice RussellFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.).
Mauro PerrettiFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.).
D Neil GrangerFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.).
Felicity N E GavinsFrom Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport (S.A.V., P.M.H., J.R., D.N.G., F.N.E.G.); Department for General and Visceral Surgery, University Hospital Muenster, Germany (F.B.); William Harvey Research Institute, Queen Mary University of London, UK (M.P.); and Division of Brain Sciences, Imperial College London, UK (F.N.E.G.). fgavin@lsuhsc.edu.
University Hospital Münster · DEQueen Mary University of London · GBWilliam Harvey Research Institute · GB

Funding

Cerebral Microvascular Dysfunction in Sickle Cell DiseaseR56HL125572 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI GAVINS, FELICITY NICOLA EMMA · 2015 to 2015
$363k
NHLBI NIH HHS R56 HL125572Wellcome Trust
6 · The paper itself

Abstract

backgroundPlatelet activation at sites of vascular injury is essential for hemostasis, but it is also a major pathomechanism underlying ischemic injury. Because anti-inflammatory therapies limit thrombosis and antithrombotic therapies reduce vascular inflammation, we tested the therapeutic potential of 2 proresolving endogenous mediators, annexin A1 N-terminal derived peptide (AnxA1Ac2-26) and aspirin-triggered lipoxin A4 (15-epi-lipoxin A4), on the cerebral microcirculation after ischemia/reperfusion injury. Furthermore, we tested whether the lipoxin A4 receptor formyl-peptide receptor 2/3 (Fpr2/3; ortholog to human FPR2/lipoxin A4 receptor) evoked neuroprotective functions after cerebral ischemia/reperfusion injury. METHODS AND

resultsUsing intravital microscopy, we found that cerebral ischemia/reperfusion injury was accompanied by neutrophil and platelet activation and neutrophil-platelet aggregate formation within cerebral microvessels. Moreover, aspirin-triggered lipoxin A4 activation of neutrophil Fpr2/3 regulated neutrophil-platelet aggregate formation in the brain and inhibited the reactivity of the cerebral microvasculature. The same results were obtained with AnxA1Ac2-26 administration. Blocking Fpr2/lipoxin A4 receptor with the antagonist Boc2 reversed this effect, and treatments were ineffective in Fpr2/3 knockout mice, which displayed an exacerbated disease severity, evidenced by increased infarct area, blood-brain barrier dysfunction, increased neurological score, and elevated levels of cytokines. Furthermore, aspirin treatment significantly reduced cerebral leukocyte recruitment and increased endogenous levels of aspirin-triggered lipoxin A4, effects again mediated by Fpr2/3.

conclusionFpr2/lipoxin A4 receptor is a therapeutic target for initiating endogenous proresolving, anti-inflammatory pathways after cerebral ischemia/reperfusion injury.

Indexed as

Amino Acid SequenceAnimalsAnnexin A1Cardiovascular DiseasesCerebral InfarctionInflammationMiceMice, Inbred C57BLMice, KnockoutNeutrophilsReceptors, Formyl PeptideAnnexin A1formyl peptide receptor 2, mouseFpr1 protein, mouseFPR3 protein, humanReceptors, Formyl Peptideinflammationischemia reperfusion injurystroke, ischemic

Identifiers

PMID27154726
PMCPMC4889496
OpenAlexW2346810793

What OpenQuestion holds

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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.