Fig. 1

Cholinergic nerve signaling promotes neonatal heart regeneration and adult heart remodeling following cardiac injury. a The neonatal mouse heart is capable of regenerating following injury, and this regenerative response was demonstrated to be dependent on cholinergic nerve signaling for proper heart regeneration. Pharmacological and mechanical blocking of cholinergic nerves resulted in reduced cardiomyocyte proliferation and failure to regenerate. b Adults with chronic heart failure treated with vagus nerve stimulation showed some improvements in heart function although these clinical studies were preliminary. The mechanisms behind the beneficial role of vagus nerve stimulation in cardiac repair are still not fully understood. However, it is suggested that the beneficial effect of VNS is partly mediated via increased ACh signaling in macrophages through binding to the α 7nAChR. This ultimately results in decreased secretion of pro-inflammatory cytokines and subsequent decrease in the heart’s fibrotic remodeling response