Evidence map›Paper›PMID 35688158›Full record

ArticleDevelopmental cell2022

Macrophages trigger cardiomyocyte proliferation by increasing epicardial vegfaa expression during larval zebrafish heart regeneration.

Finnius A Bruton, Aryan Kaveh, Katherine M Ross-Stewart, Gianfranco Matrone, Magdalena E M Oremek, Emmanouil G Solomonidis, Carl S Tucker, John J Mullins, Christopher D Lucas, Mairi Brittan and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Dynamic cardiac hyperplasia and hypertrophy in Burmese pythons.American journal of physiology. Cell physiology · 2026
    Article
  4. Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026
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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

13 authors at 5 institutions in 2 countries.

Finnius A BrutonCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK. Electronic address: fbruton@ed.ac.uk.
Aryan KavehCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Katherine M Ross-StewartCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Gianfranco MatroneCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Magdalena E M OremekCentre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Emmanouil G SolomonidisCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Carl S TuckerCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
John J MullinsCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Christopher D LucasCentre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Mairi BrittanCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Jonathan M TaylorDepartment of Physics, University of Glasgow, Glasgow G12 8QQ, UK.
Adriano G RossiCentre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Martin A DenvirCentre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
University of Edinburgh · GBThe Queen's Medical Research Institute · GBCentre for Inflammation Research · GBQueen's Medical Centre · GBUniversity of Glasgow · GB

Funding

British Heart Foundation NH/14/2/31074British Heart Foundation RE/13/3/30183Medical Research Council MR/K013386/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/P002196/1
6 · The paper itself

Abstract

Cardiac injury leads to the loss of cardiomyocytes, which are rapidly replaced by the proliferation of the surviving cells in zebrafish, but not in mammals. In both the regenerative zebrafish and non-regenerative mammals, cardiac injury induces a sustained macrophage response. Macrophages are required for cardiomyocyte proliferation during zebrafish cardiac regeneration, but the mechanisms whereby macrophages facilitate this crucial process are fundamentally unknown. Using heartbeat-synchronized live imaging, RNA sequencing, and macrophage-null genotypes in the larval zebrafish cardiac injury model, we characterize macrophage function and reveal that these cells activate the epicardium, inducing cardiomyocyte proliferation. Mechanistically, macrophages are specifically recruited to the epicardial-myocardial niche, triggering the expansion of the epicardium, which upregulates vegfaa expression to induce cardiomyocyte proliferation. Our data suggest that epicardial Vegfaa augments a developmental cardiac growth pathway via increased endocardial notch signaling. The identification of this macrophage-dependent mechanism of cardiac regeneration highlights immunomodulation as a potential strategy for enhancing mammalian cardiac repair.

Indexed as

Myocytes, CardiacZebrafishAnimalsCell ProliferationHeartLarvaMacrophagesMammalsZebrafish ProteinsZebrafish Proteinsepicardiumheartmacrophagesnotchregenerationrepairvegfzebrafish

Identifiers

PMID35688158
PMCPMC9616726
OpenAlexW4282013077

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.