Evidence map›Paper›PMID 25001623›Full record

ArticleCirculation2014

ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis.

Kyung-Sun Heo, Hannah J Cushman, Masashi Akaike, Chang-Hoon Woo, Xin Wang, Xing Qiu, Keigi Fujiwara, Jun-ichi Abe

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

Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

47 citing papers in PubMed, 81 citations in OpenAlex.

  1. Trial
  2. Article
  3. Efferocytosis-associated Mrc1Frontiers in immunology · 2026
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Mechanism of efferocytosis in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2024
    Review
  13. Article
  14. Article
  15. Biomechanics-mediated endocytosis in atherosclerosis.Frontiers in cardiovascular medicine · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review
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

8 authors at 2 institutions in 2 countries.

Kyung-Sun HeoFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.). Kyung-Sun_Heo@urmc.rochester.edu Jun-ichi_Abe@urmc.rochester.edu.
Hannah J CushmanFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.).
Masashi AkaikeFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.).
Chang-Hoon WooFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.).
Xin WangFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.).
Xing QiuFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.).
Keigi FujiwaraFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.).
Jun-ichi AbeFrom the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (K.H., H.J.C., C.W., K.F., J.A.); Department of Medical Education, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan (M.A.); Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom (X.W.); and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY (X.Q.). Kyung-Sun_Heo@urmc.rochester.edu Jun-ichi_Abe@urmc.rochester.edu.
Tokushima University · JPUniversity of Manchester · GB

Funding

FLUID SHEAR STRESS SIGNAL TRANSDUCTION IN ENDOTHELIUMR01HL064839 · NHLBI · UNIVERSITY OF ROCHESTER · PI ABE, JUN-ICHI, BERK, BRADFORD C · 2001 to 2013
$4.8M
p90RSK-ERK5 module, efferocytosis, and vulnerable plaque formationR01HL118462 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ABE, JUN-ICHI · 2014 to 2018
$2.0M
p90RSK: A flow responsive mediator of inflammationR01HL102746 · NHLBI · UNIVERSITY OF ROCHESTER · PI ABE, JUN-ICHI, FUJIWARA, KEIGI · 2010 to 2013
$1.7M
Ubiquitin-like protein modification in diabetic cardiomyopathyR01HL108551 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ABE, JUN-ICHI · 2011 to 2014
$1.6M
British Heart Foundation PG/09/052/27833British Heart Foundation PG/12/76/29852NHLBI NIH HHS HL-064839NHLBI NIH HHS HL-102746NHLBI NIH HHS HL-108551NHLBI NIH HHS R01 HL064839NHLBI NIH HHS R01 HL102746NHLBI NIH HHS R01 HL108551NHLBI NIH HHS R01 HL118462
6 · The paper itself

Abstract

backgroundEfferocytosis is a process by which dead and dying cells are removed by phagocytic cells. Efferocytosis by macrophages is thought to curb the progression of atherosclerosis, but the mechanistic insight of this process is lacking. METHODS AND

resultsWhen macrophages were fed apoptotic cells or treated with pitavastatin in vitro, efferocytosis-related signaling and phagocytic capacity were upregulated in an ERK5 activity-dependent manner. Macrophages isolated from macrophage-specific ERK5-null mice exhibited reduced efferocytosis and levels of gene and protein expression of efferocytosis-related molecules. When these mice were crossed with low-density lipoprotein receptor(-/-) mice and fed a high-cholesterol diet, atherosclerotic plaque formation was accelerated, and the plaques had more advanced and vulnerable morphology.

conclusionsOur results demonstrate that ERK5, which is robustly activated by statins, is a hub molecule that upregulates macrophage efferocytosis, thereby suppressing atherosclerotic plaque formation. Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases.

Indexed as

AnimalsAtherosclerosisCells, CulturedEnzyme ActivationMacrophagesMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 7PhagocytosisMitogen-Activated Protein Kinase 7atherosclerosissignal transduction

Identifiers

PMID25001623
PMCPMC4439099
OpenAlexW2070108190

What OpenQuestion holds

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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.