Blocking Axonal Transportation of Neurotrophin Prevents Myocardial Infarction Induced Sympathetic and Cardiac Remodeling

Background: Nerve growth factor (NGF) and growth associated protein 43 (GAP43) are dramatically increased in damaged tissue after myocardial infarction (MI) and proposed to retrogradely transport to left stellate ganglion (LSG). In this study, we determine whether local ablation of cardiac sympathetic nerves is able to block the neurothrophin transportation. Methods and results: Forty rabbits were randomly assigned into the sham-operated, MI and MI-ablation groups. Three days after operation, the levels of NGF and GAP43 were determined in each group. In MI group, the protein of NGF and GAP43 were both elevated in infarcted border zone (IBZ) and LSG. The elevation of GAP43 protein was correlated with the increase of its mRNA levels in both areas. However, the elevation of NGF mRNA was displayed only in IBZ, not in LSG, suggesting that the increase of NGF protein in LSG was possibly due to its retrograde transportation from IBZ. Furthermore, local ablation of sympathetic nerves leading to no increase of NGF protein in LSG post MI. Correspondingly, GAP43 protein and mRNA were not increased in LSG, and slightly elevated in IBZ, suggesting the upregulation of GAP43 in IBZ is subjected to the influence of promoting signal from LSG. Four weeks later, immunohistochemistry showed MI caused pronounced GAP43 and tyrosine hydroxylase positive nerves in cardiac tissue, especially in IBZ, which could be precluded by ablation. Conclusion: The local ablation of cardiac sympathetic nerves blocks neurotrophin transportation from damaged tissue to LSG post MI, and inhibits nerve sprouting, sympathetic hyperinnervation and cardiac remodeling.