Defining Cardiac Nerve Architecture During Development, Disease, and Regeneration

Abstract

Cardiac nerves regulate neonatal mouse heart regeneration and are susceptible to pathological remodeling following adult injury. Understanding cardiac nerve remodeling can lead to new strategies to promote cardiac repair. Our current understanding of cardiac nerve architecture has been limited to two-dimensional analysis. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling tools to define cardiac nerve architecture and neurovascular association during development, disease, and regeneration. Our results demonstrate that cardiac nerves sequentially associate with coronary veins and arteries during development. Remarkably, our results reveal that parasympathetic nerves densely innervate the ventricles. Furthermore, parasympathetic and sympathetic nerves develop synchronously and are intertwined throughout the ventricles. Importantly, the regenerating myocardium reestablishes physiological innervation, in stark contrast to the non-regenerating heart. Mechanistically, reinnervation during regeneration is dependent on collateral artery formation. Our results reveal how defining cardiac nerve remodeling during homeostasis, disease, and regeneration can identify new therapies for cardiac disease.

The significance of heart rate variability in patients with frequent premature ventricular complex originating from the ventricular outflow tract

“…While both the RVOT and the aortic root contain ample ganglia plexus, 15 recent study has also highlighted the crucial role of cardiac parasympathetic nerves in ventricles. 30 Thus, our study underscores the importance of cardiac ANS imbalance in the pathophysiology of RVOT-PVCs.…”

CXCL12drives natural variation in coronary artery anatomy across diverse populations

“…Animal models have also shown that Cxcl12 stimulates coronary repair and regeneration. Neonatal mouse heart regeneration is enabled after myocardial infarction by capillary induction of Cxcl12, which signals to artery cells and guides their migration to a location where they can form natural collateral artery bypasses that support reinnervation [48][49][50] . In adult mouse hearts, which don't regenerate, a single localized injection of CXCL12 stimulates revascularization myocardial recovery 48,51,52 .…”