Evidence map›Paper›PMID 33779682›Full record

ArticleThe Journal of experimental medicine2021

Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms.

Frank M Davis, Lam C Tsoi, William J Melvin, Aaron denDekker, Rachael Wasikowski, Amrita D Joshi, Sonya Wolf, Andrea T Obi, Allison C Billi, Xianying Xing and 7 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
13.5field-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

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Palmitic Acid Amplifies Microglial Inflammatory Activation Involving C5aR1-Sensitive Inflammatory Signaling and JMJD3/H3K27me3-Related Epigenetic Changes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Article
  6. Article
  7. Review
  8. 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
  9. Article
  10. Article
  11. Monocyte-mediated mechanisms in idiopathic pulmonary fibrosis: opportunities for early intervention.Apoptosis : an international journal on programmed cell death · 2026
    Review
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  20. bioRxiv : the preprint server for biology · 2025
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Frank M DavisSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Lam C TsoiDepartment of Dermatology, University of Michigan, Ann Arbor, MI.
William J MelvinSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Aaron denDekkerSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Rachael WasikowskiDepartment of Dermatology, University of Michigan, Ann Arbor, MI.
Amrita D JoshiSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Sonya WolfSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Andrea T ObiSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Allison C BilliDepartment of Dermatology, University of Michigan, Ann Arbor, MI.
Xianying XingDepartment of Dermatology, University of Michigan, Ann Arbor, MI.
Christopher AuduSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Bethany B MooreDepartment Microbiology and Immunology, University of Michigan, Ann Arbor, MI.
Steven L KunkelDepartment of Pathology, University of Michigan, Ann Arbor, MI.
Alan DaughertyDepartment of Physiology, Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY.
Hong S LuDepartment of Physiology, Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY.
Johann E GudjonssonDepartment of Dermatology, University of Michigan, Ann Arbor, MI.
Katherine A GallagherSection of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
University of Michigan · USUniversity of Kentucky · US

Funding

University of Michigan Skin Biology and Diseases Resource-based CenterP30AR075043 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANDRZEJ A. DLUGOSZ · 2019 to 2026
$6.6M
Immunobiology of Lung Injury and FibrosisR35HL144481 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOORE, BETHANY B. · 2019 to 2024
$5.2M
Targeting jmjd3 mitigates heterotopic ossificationR01AR079863 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Katherine Ann Gallagher, Benjamin Levi · 2021 to 2026
$3.0M
Notch signaling in diabetic woundsR01DK127531 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN · 2021 to 2024
$2.5M
The Interferon-beta (IFN-beta)/SETDB2 Epigenetic Axis Regulates Inflammation And Metabolism In Diabetic WoundsR01HL137919 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN · 2017 to 2021
$2.4M
Role of IL-13 and the IL-13 Associated rs20541 Risk Variant in the Pathogenesis of PsoriasisR01AR069071 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GUDJONSSON, JOHANN ELI · 2015 to 2019
$2.1M
Epigenetic Regulation of Prostaglandin E2 (PGE2) Synthesis Alters Macrophage Function to Promote Inflammation and Impair Diabetic Wound HealingR01DK124290 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN, MOORE, BETHANY B. · 2020 to 2023
$1.8M
JMJD3 Regulates Abdominal Aortic Aneurysm ExpansionR01HL156274 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GALLAGHER, KATHERINE ANN · 2021 to 2022
$1.1M
Palmitate Regulates JMJD3 Epigenetic Alterations in Macrophages and Directs Wound HealingF32DK117545 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVIS, FRANK MICHAEL · 2018 to 2019
$128k
NHLBI NIH HHS R01 HL137919NHLBI NIH HHS R01 HL156274NHLBI NIH HHS R35 HL144481NIAMS NIH HHS P30 AR075043NIAMS NIH HHS R01 AR069071NIAMS NIH HHS R01 AR079863NIDDK NIH HHS F32 DK117545NIDDK NIH HHS R01 DK124290NIDDK NIH HHS R01 DK127531
6 · The paper itself

Abstract

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB-mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II-induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.

Indexed as

Angiotensin IIAnimalsAortic Aneurysm, AbdominalDisease Models, AnimalHistone DemethylasesInflammationInflammation MediatorsJumonji Domain-Containing Histone DemethylasesMacrophagesMaleMiceMice, Inbred C57BLNF-kappa BUp-RegulationAngiotensin IIHistone DemethylasesInflammation MediatorsJumonji Domain-Containing Histone DemethylasesKdm6b protein, mouseNF-kappa B

Identifiers

PMID33779682
PMCPMC8008365
OpenAlexW3151923718

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.