Spatial distribution of nerve sprouting after myocardial infarction in mice

Abstract

Background: Myocardial infarction (MI) elicits nerve sprouting. Objectives: The purpose of this study was to determine the spatial distribution of nerve sprouting and neurotrophic gene expression after MI. Methods: We created MI in mice by coronary artery ligation. The hearts were removed 3 hours to 2 months after MI and examined for nerve fiber density and neurotrophic factor gene expression using Affymetrix microarray and mRNA analyses. Results: The density of nerve fibers immunopositive for growth-associated protein (GAP)-43 was the highest 3 hours after MI both in the peri-infarct area and in the area remote to infarct, resulting in sympathetic (but not parasympathetic) hyperinnervation in the ventricles. The GAP-43-positive nerve fiber density of myocardium was greater in the outer transverse loop than in the inner vertical loop. The differences between these two myocardial loops peaked within 3 hours after MI and persisted for 2 months afterward. Gene expression of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-β3, and interleukin-1α was increased up to 2 months after MI compared with normal control. Expression of these growth factors was more pronounced and persistent in the peri-infarct area than in the remote area. Conclusion: MI induces sympathetic nerve sprouting in both peri-infarct and remote areas, more in the outer transverse loop. Selective up-regulation of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-β3, and interleukin-1α occurred in the peri-infarct area and, to a lesser extent, in the remote area. © 2006 Heart Rhythm Society.