Macrophages trigger cardiomyocyte proliferation by increasing epicardial vegfaa expression during larval zebrafish heart regeneration.
epicardium
heart
macrophages
notch
regeneration
repair
vegf
zebrafish
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
20 06 2022
20 06 2022
Historique:
received:
09
08
2021
revised:
11
02
2022
accepted:
18
05
2022
pubmed:
11
6
2022
medline:
24
6
2022
entrez:
10
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35688158
pii: S1534-5807(22)00371-9
doi: 10.1016/j.devcel.2022.05.014
pmc: PMC9616726
pii:
doi:
Substances chimiques
Zebrafish Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1512-1528.e5Subventions
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/P002196/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K013386/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : NH/14/2/31074
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/13/3/30183
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests
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