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Parasympathetic and sympathetic axons are bundled in the cardiac ventricles and undergo physiological reinnervation during heart regeneration.

ABSTRACT: Sympathetic innervation influences homeostasis, repair, and pathology in the cardiac ventricles; in contrast, parasympathetic innervation is considered to have minimal contribution and influence in the ventricles. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling to define cardiac nerve architecture during development, disease, and regeneration. Our approach reveals that parasympathetic nerves extensively innervate the cardiac ventricles. Furthermore, we identify that parasympathetic and sympathetic axons develop synchronously and are bundled throughout the ventricles. We further investigate cardiac nerve remodeling in the regenerative neonatal and the non-regenerative postnatal mouse heart. Our results show that the regenerating myocardium undergoes a unique process of physiological reinnervation, where proper nerve distribution and architecture is reestablished, in stark contrast to the non-regenerating heart. Mechanistically, we demonstrate that physiological reinnervation during regeneration is dependent on collateral artery formation. Our results reveal clinically significant insights into cardiac nerve plasticity which can identify new therapies for cardiac disease.

SUBMITTER: Salamon RJ

PROVIDER: S-EPMC10477065 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Parasympathetic and sympathetic axons are bundled in the cardiac ventricles and undergo physiological reinnervation during heart regeneration.

Salamon Rebecca J RJ Halbe Poorva P Kasberg William W Bae Jiyoung J Audhya Anjon A Mahmoud Ahmed I AI

iScience 20230825 10

Sympathetic innervation influences homeostasis, repair, and pathology in the cardiac ventricles; in contrast, parasympathetic innervation is considered to have minimal contribution and influence in the ventricles. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling to define cardiac nerve architecture during development, disease, and regeneration. Our approach reveals that parasympathetic nerves extensively innervate the cardiac ventricles. Furthermore, we identify t ...[more]

PMID: 37674983

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Project description:Variants in transcription factor 7-like 2 (266096218TCF7L2266096218USuser266096218Gene names have been italicized per house style. Please check and confirm whether there are other instances that need to be italicized or instances where italics have been inappropriately applied.) gene have been found strongly associated with an increased risk of type 2 diabetes, as well as with an impairment of glucagon-like peptide-1 (GLP-1) signalling chain. In rats, stimulation of central GLP-1 receptors increases heart rate and activates autonomic regulatory neurons. We aimed to evaluate the potential role of TCF7L2 gene polymorphisms on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration after glucose ingestion. Genotyping was performed for rs12255372 and rs7903146 TCF7L2 gene variants in 250 non-related healthy volunteers (mean age 27±3 years). Consistent with previous reports, both single-nucleotide polymorphisms were in strong linkage disequilibrium (D'=0.87, r(2)=0.76). A subset of 167 patients underwent an oral glucose tolerance test while a continuous recording of heart rate variability was performed. At baseline, no differences in fasting plasma insulin, in GLP-1 levels and in LF/HF (low frequency/high frequency) ratio between the three genotypes were found. Along with glucose ingestion TT subjects had lower INS(AUC) (insulin area under curve), as well as higher LF/HF(AUC) (LF/HF area under curve) values. No difference in GLP-1(AUC) (GLP-1 area under curve) between TCF7L2 gene variants was found. A multivariate analysis including multiple covariates showed that only INS(AUC,) GLP-1(AUC) and TCF7L2 gene variants were independently associated with LF/HF(AUC). In conclusion, TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity. Moreover, such effect is independent of GLP-1 and insulin plasma concentrations suggesting a potential role of such gene variants in increasing cardiovascular risk through enhanced sympathetic nervous system activity.

Dataset Information

Parasympathetic and sympathetic axons are bundled in the cardiac ventricles and undergo physiological reinnervation during heart regeneration.

Publications

Parasympathetic and sympathetic axons are bundled in the cardiac ventricles and undergo physiological reinnervation during heart regeneration.

Similar Datasets

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