Targeting calcineurin induces cardiomyocyte proliferation in adult mice.
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
25
10
2021
accepted:
07
06
2022
medline:
1
7
2022
pubmed:
1
7
2022
entrez:
28
8
2024
Statut:
ppublish
Résumé
The mammalian neonatal heart can regenerate for 1 week after birth, after which, the majority of cardiomyocytes exit the cell cycle. Recent studies demonstrated that calcineurin mediates cell-cycle arrest of postnatal cardiomyocytes, partly through induction of nuclear translocation of the transcription factor Hoxb13 (a cofactor of Meis1). Here we show that inducible cardiomyocyte-specific deletion of calcineurin B1 in adult cardiomyocytes markedly decreases cardiomyocyte size and promotes mitotic entry, resulting in increased total cardiomyocyte number and improved left ventricular (LV) systolic function after myocardial infarction (MI). Similarly, pharmacological inhibition of calcineurin activity using FK506 promotes cardiomyocyte proliferation in vivo and increases cardiomyocyte number; however, FK506 administration after MI in mice failed to improve LV systolic function, possibly due to inhibition of vasculogenesis and blunting of the post-MI inflammatory response. Collectively, our results demonstrate that loss of calcineurin activity in adult cardiomyocytes promotes cell cycle entry; however, the effects of the calcineurin inhibitor FK506 on other cell types preclude a significant improvement of LV systolic function after MI.
Identifiants
pubmed: 39196243
doi: 10.1038/s44161-022-00098-6
pii: 10.1038/s44161-022-00098-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
679-688Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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