Evidence map›Paper›PMID 24625784›Full record

ArticleCirculation research2014

Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium.

Ingo Hilgendorf, Louisa M S Gerhardt, Timothy C Tan, Carla Winter, Tobias A W Holderried, Benjamin G Chousterman, Yoshiko Iwamoto, Ronglih Liao, Andreas Zirlik, Marielle Scherer-Crosbie and 5 more

Open access · bronzeAbstract read
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In one paragraph

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 363 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
363citing papers in PubMed, 3 pooled it
20.2field-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

363 citing papers in PubMed, 3 syntheses or guidelines pooled it, 531 citations in OpenAlex.

  1. Pooled it
  2. Myocardial Immune Cells: The Basis of Cardiac Immunology.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Pooled it
  3. Pooled it
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  10. S100A8/S100A9 released by CD11bExperimental & molecular medicine · 2026
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  11. Macrophages and the Survival of Cardiomyocytes After Myocardial Infarction.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  12. Article
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  16. Article
  17. Article
  18. Review
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  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Ingo HilgendorfFrom the Center for Systems Biology (I.H., L.M.S.G., C.W., B.G.C., Y.I., M.N., R.W., F.K.S.) and Department of Cardiology (T.C.T., M.S.-C.), Massachusetts General Hospital, Boston; Department of Gastroenterology, Hepatology, and Infectious Diseases, University of Duesseldorf, Duesseldorf, Germany (T.A.W.H.); Department of Medicine (R.L.) and Cardiovascular Division, Department of Medicine (P.L.), Brigham and Women's Hospital, Boston, MA; Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany (A.Z.); Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, CA (C.C.H.); and Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.).
Louisa M S Gerhardt
Timothy C Tan
Carla Winter
Tobias A W Holderried
Benjamin G Chousterman
Yoshiko Iwamoto
Ronglih Liao
Andreas Zirlik
Marielle Scherer-Crosbie
Catherine C Hedrick
Peter Libby
Matthias Nahrendorf
Ralph Weissleder
Filip K Swirski
Harvard University · USHeinrich Heine University Düsseldorf · DEUniversitäts-Herzzentrum Freiburg-Bad Krozingen · DECenter for Systems Biology · USLa Jolla Institute for Immunology · US

Funding

Monocyte Heterogeneity in Experimental and Human AtherosclerosisR01HL095612 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SWIRSKI, FILIP K · 2009 to 2016
$3.4M
Innate Response Activator B cells in Bacterial Lung InfectionR56AI104695 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SWIRSKI, FILIP K · 2013 to 2013
$403k
NHLBI NIH HHS 1R01HL095612NHLBI NIH HHS R01 HL095612NIAID NIH HHS R56 AI104695NIAID NIH HHS R56AI104695
6 · The paper itself

Abstract

rationaleHealing after myocardial infarction involves the biphasic accumulation of inflammatory lymphocyte antigen 6C (Ly-6C)(high) and reparative Ly-6C(low) monocytes/macrophages (Mo/MΦ). According to 1 model, Mo/MΦ heterogeneity in the heart originates in the blood and involves the sequential recruitment of distinct monocyte subsets that differentiate to distinct macrophages. Alternatively, heterogeneity may arise in tissue from 1 circulating subset via local macrophage differentiation and polarization. The orphan nuclear hormone receptor, nuclear receptor subfamily 4, group a, member 1 (Nr4a1), is essential to Ly-6C(low) monocyte production but dispensable to Ly-6C(low) macrophage differentiation; dependence on Nr4a1 can thus discriminate between systemic and local origins of macrophage heterogeneity.

objectiveThis study tested the role of Nr4a1 in myocardial infarction in the context of the 2 Mo/MΦ accumulation scenarios. METHODS AND

resultsWe show that Ly-6C(high) monocytes infiltrate the infarcted myocardium and, unlike Ly-6C(low) monocytes, differentiate to cardiac macrophages. In the early, inflammatory phase of acute myocardial ischemic injury, Ly-6C(high) monocytes accrue in response to a brief C-C chemokine ligand 2 burst. In the second, reparative phase, accumulated Ly-6C(high) monocytes give rise to reparative Ly-6C(low) F4/80(high) macrophages that proliferate locally. In the absence of Nr4a1, Ly-6C(high) monocytes express heightened levels of C-C chemokine receptor 2 on their surface, avidly infiltrate the myocardium, and differentiate to abnormally inflammatory macrophages, which results in defective healing and compromised heart function.

conclusionsLy-6C(high) monocytes orchestrate both inflammatory and reparative phases during myocardial infarction and depend on Nr4a1 to limit their influx and inflammatory cytokine expression.

Indexed as

AnimalsAntigens, LyCell MovementFemaleInflammationInflammation MediatorsMiceMice, Inbred C57BLMice, KnockoutMonocytesMyocardial InfarctionNuclear Receptor Subfamily 4, Group A, Member 1Antigens, LyInflammation MediatorsLy-6C antigen, mouseNr4a1 protein, mouseNuclear Receptor Subfamily 4, Group A, Member 1hormone receptorsmacrophagesmonocytesmyocardial infarctionnuclear

Identifiers

PMID24625784
PMCPMC4017349
OpenAlexW2157758580

What OpenQuestion holds

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Registered trials

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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.