Non-neuronal cholinergic system delays cardiac remodelling in type 1 diabetes.

Autor:	Munasinghe PE; Department of Physiology, HeartOtago, University of Otago, 270, Great King Street, Dunedin, 9010, New Zealand., Saw EL; Department of Physiology, HeartOtago, University of Otago, 270, Great King Street, Dunedin, 9010, New Zealand., Reily-Bell M; Department of Physiology, HeartOtago, University of Otago, 270, Great King Street, Dunedin, 9010, New Zealand., Tonkin D; Department of Physiology, HeartOtago, University of Otago, 270, Great King Street, Dunedin, 9010, New Zealand., Kakinuma Y; Department of Bioregulatory Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan., Fronius M; Department of Bioregulatory Science, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan., Katare R; Department of Physiology, HeartOtago, University of Otago, 270, Great King Street, Dunedin, 9010, New Zealand.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2023 Jun 19; Vol. 9 (6), pp. e17434. Date of Electronic Publication: 2023 Jun 19 (Print Publication: 2023).
DOI:	10.1016/j.heliyon.2023.e17434
Abstrakt:	Aims: 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. Methods: 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. Key Findings: 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. Significance: 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. Competing Interests: 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. (© 2023 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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