GCN5 contributes to intracellular lipid accumulation in human primary cardiac stromal cells from patients affected by Arrhythmogenic cardiomyopathy.
Arrhythmogenic cardiomyopathy
cellular redox mechanisms
histone acetyltransferase GCN5
human cardiac stromal cells
intracellular lipid accumulation
reactive oxygen species
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
revised:
20
03
2022
received:
22
12
2021
accepted:
28
04
2022
pubmed:
18
6
2022
medline:
9
7
2022
entrez:
17
6
2022
Statut:
ppublish
Résumé
Arrhythmogenic cardiomyopathy (ACM) is a genetic disease associated with sudden cardiac death and cardiac fibro-fatty replacement. Over the last years, several works have demonstrated that different epigenetic enzymes can affect not only gene expression changes in cardiac diseases but also cellular metabolism. Specifically, the histone acetyltransferase GCN5 is known to facilitate adipogenesis and modulate cardiac metabolism in heart failure. Our group previously demonstrated that human primary cardiac stromal cells (CStCs) contribute to adipogenesis in the ACM pathology. Thus, this study aims to evaluate the role of GCN5 in ACM intracellular lipid accumulation. To do so, CStCs were obtained from right ventricle biopsies of ACM patients and from samples of healthy cadaveric donors (CTR). GCN5 expression was increased both in ex vivo and in vitro ACM samples compared to CTR. When GCN5 expression was silenced or pharmacologically inhibited by the administration of MB-3, we observed a reduction in lipid accumulation and a mitigation of reactive oxygen species (ROS) production in ACM CStCs. In agreement, transcriptome analysis revealed that the presence of MB-3 modified the expression of pathways related to cellular redox balance. Altogether, our findings suggest that GCN5 inhibition reduces fat accumulation in ACM CStCs, partially by modulating intracellular redox balance pathways.
Identifiants
pubmed: 35712781
doi: 10.1111/jcmm.17396
pmc: PMC9258704
doi:
Substances chimiques
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3687-3701Subventions
Organisme : Joint Project SüdTyrol- FWF (Italy-Austria)
ID : 23623
Organisme : Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol (Italy)
Organisme : Italian Ministry of Health
ID : RC2019 EF5C ID:2754330
Informations de copyright
© 2022 EURAC Research. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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