Evidence map›Paper›PMID 29472233›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic Aneurysms.

Akshaya K Meher, Michael Spinosa, John P Davis, Nicolas Pope, Victor E Laubach, Gang Su, Vlad Serbulea, Norbert Leitinger, Gorav Ailawadi, Gilbert R Upchurch

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 2 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

168 citing papers in PubMed, 2 syntheses or guidelines pooled it, 246 citations in OpenAlex.

  1. Pooled it
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  11. Protectin D1/GPR37 Signaling Enhances Macrophage-Dependent Efferocytosis to Attenuate Experimental Abdominal Aortic Aneurysm Formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  12. The role of neutrophils in the pathogenesis of abdominal aortic aneurysms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
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  18. Review
  19. Neutrophil extracellular traps in cancer.Nature reviews. Cancer · 2026
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Akshaya K MeherFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville. am5bv@virginia.edu.
Michael SpinosaFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
John P DavisFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Nicolas PopeFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Victor E LaubachFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Gang SuFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Vlad SerbuleaFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Norbert LeitingerFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Gorav AilawadiFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Gilbert R UpchurchFrom the Department of Surgery (A.K.M., M.S., J.P.D., N.P., V.E.L., G.S., G.A., G.R.U.), Department of Pharmacology (A.K.M., V.S., N.L.), Robert M. Berne Cardiovascular Research Center (A.K.M., N.L., G.A., G.R.U.), Department of Molecular Physiology and Biological Physics (G.R.U.), and Department of Biomedical Engineering (G.A.), University of Virginia, Charlottesville.
Dr. M.G.R. Educational and Research Institute · INMACOM (United States) · US

Funding

TRAINING IN THE PHARMACOLOGICAL SCIENCEST32GM007055 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LYNCH, KEVIN R. · 1985 to 2022
$7.2M
The Role of IL-1R1 in cell transitions in Aortic Aneurysm PathogenesisR01HL126668 · NHLBI · UNIVERSITY OF VIRGINIA · PI AILAWADI, GORAV · 2015 to 2019
$2.4M
Role of Neutrophil Extracellular Traps in AAA PathogenesisR01HL124131 · NHLBI · UNIVERSITY OF VIRGINIA · PI UPCHURCH, GILBERT RIVERS · 2014 to 2017
$1.6M
Role of Dab2 in Fatty Liver DiseaseR01DK096076 · NIDDK · UNIVERSITY OF VIRGINIA · PI LEITINGER, NORBERT · 2013 to 2016
$1.4M
NHLBI NIH HHS R01 HL124131NHLBI NIH HHS R01 HL126668NIDDK NIH HHS R01 DK096076NIGMS NIH HHS T32 GM007055
6 · The paper itself

Abstract

objectiveNeutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1β in the formation of murine experimental AAAs. Here, the hypothesis that IL-1β-induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested. APPROACH AND

resultsNETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry. NETs were detected in human AAAs and were colocalized with IL-1β. In vitro, IL-1RA attenuated IL-1β-induced NETosis in human neutrophils. Mechanistically, IL-1β treatment of isolated neutrophils induced nuclear localization of ceramide synthase 6 and synthesis of C16-ceramide, which was inhibited by IL-1RA or fumonisin B1, an inhibitor of ceramide synthesis. Furthermore, IL-1RA or fumonisin B1 attenuated IL1-β-induced NETosis. In an experimental model of murine AAA, NETs were detected at a very early stage-day 3 of aneurysm induction. IL-1β-knockout mice demonstrated significantly lower infiltration of neutrophils to aorta and were protected from AAA. Adoptive transfer of wild-type neutrophils promoted AAA formation in IL-1β-knockout mice. Moreover, treatment of wild-type mice with Cl-amidine, an inhibitor NETosis, significantly attenuated AAA formation, whereas, treatment with deoxyribonuclease, a DNA digesting enzyme, had no effect on AAA formation.

conclusionsAltogether, the results suggest a dominant role of IL-1β-induced NETosis in AAA formation.

Indexed as

AnimalsAorta, AbdominalAortic Aneurysm, AbdominalCeramidesDisease Models, AnimalExtracellular TrapsHumansImage Processing, Computer-AssistedInterleukin-1betaMembrane ProteinsMiceMice, KnockoutMicroscopy, FluorescenceNeutrophilsOrnithineReceptors, Interleukin-1CeramidesCERS6 protein, humanIL1B protein, humanIL1B protein, mouseInterleukin-1betaMembrane ProteinsN-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amideOrnithineReceptors, Interleukin-1Sphingosine N-Acyltransferaseaortic aneurysmextracellular trapsinterleukin-1betaneutrophils

Identifiers

PMID29472233
PMCPMC5864548
OpenAlexW2788388528

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.