Key result
Collateral artery formation drives physiological reinnervation of bundled autonomic axons in regenerating neonatal mouse myocardium.
Why the study?
Parasympathetic innervation has been considered to have minimal contribution and influence in the cardiac ventricles compared with sympathetic innervation.
Hypothesis-generating for reinnervation in cardiac regeneration; leaves open translation to adult human myocardium.
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.
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Salamon et al. (2023) studied Cardiac nerve architecture and regeneration. Parasympathetic and sympathetic axons are bundled in the cardiac ventricles, and regenerating neonatal mouse myocardium undergoes physiological reinnervation dependent on collateral artery formation.
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