Non-neuronal cholinergic system delays cardiac remodelling in type 1 diabetes.
Acetylcholine
Apoptosis
Cardiac function
Cardiac non-neuronal cholinergic system
Cardiovascular disease
Type 1 diabetes mellitus
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
26
01
2023
revised:
15
06
2023
accepted:
16
06
2023
medline:
10
7
2023
pubmed:
10
7
2023
entrez:
10
7
2023
Statut:
epublish
Résumé
Type 1 diabetes mellitus (T1DM) is associated with increased risk of cardiovascular disease (CVD) and mortality. The underlying mechanisms for T1DM-induced heart disease still remains unclear. In this study, we aimed to investigate the effects of cardiac non-neuronal cholinergic system (cNNCS) activation on T1DM-induced cardiac remodelling. T1DM was induced in C57Bl6 mice using low-dose streptozotocin. Western blot analysis was used to measure the expression of cNNCS components at different time points (4, 8, 12, and 16 weeks after T1DM induction). To assess the potential benefits of cNNCS activation, T1DM was induced in mice with cardiomyocyte-specific overexpression of choline acetyltransferase (ChAT), the enzyme required for acetylcholine (Ac) synthesis. We evaluated the effects of ChAT overexpression on cNNCS components, vascular and cardiac remodelling, and cardiac function. Western blot analysis revealed dysregulation of cNNCS components in hearts of T1DM mice. Intracardiac ACh levels were also reduced in T1DM. Activation of ChAT significantly increased intracardiac ACh levels and prevented diabetes-induced dysregulation of cNNCS components. This was associated with preserved microvessel density, reduced apoptosis and fibrosis, and improved cardiac function. Our study suggests that cNNCS dysregulation may contribute to T1DM-induced cardiac remodelling, and that increasing ACh levels may be a potential therapeutic strategy to prevent or delay T1DM-induced heart disease.
Identifiants
pubmed: 37426799
doi: 10.1016/j.heliyon.2023.e17434
pii: S2405-8440(23)04642-X
pmc: PMC10329120
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e17434Informations de copyright
© 2023 The Authors. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Rajesh Katare reports financial support was provided by 10.13039/501100001509Royal Society of New Zealand. Yoshihiko Kakinuma reports financial support was provided by 10.13039/501100001691Japan Society for the Promotion of Science. Yoshihiko Kakinuma reports financial support was provided by 10.13039/501100004330Smoking Research Foundation.
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