p75 neurotrophin receptor modulates the development and post-infarct remodeling of cardiac sympathetic neurons

Myocardial infarction (MI) affects more than one million Americans each year, and survivors face a high risk of ventricular arrhythmias and sudden cardiac death. Abnormal remodeling of the sympathetic nervous system, characterized by regions of hyperinnervation and denervation in the viable myocardium, contributes to this vulnerability. While excess nerve growth factor explains post MI hyperinnervation, the cause of sympathetic denervation remains unclear. Recent evidence shows that activation of the p75 neurotrophin receptor (p75NTR) by brain derived neurotrophic factor (BDNF) triggers sympathetic axon degeneration. Because BDNF is transiently upregulated after MI, I hypothesized that p75NTR mediated signaling drives sympathetic denervation following myocardial infarction.