Spatial distribution of nerve sprouting after myocardial infarction in mice

Yong Seog Oh, Ambrose Y. Jong, Dave T. Kim, Hongmei Li, Charles Wang, Alice Zemljic-Harpf, Robert S. Ross, Michael C. Fishbein, Peng Sheng Chen, Lan S. Chen

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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.

Original languageEnglish (US)
Pages (from-to)728-736
Number of pages9
JournalHeart Rhythm
Volume3
Issue number6
DOIs
StatePublished - Jun 1 2006

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Keywords

  • Cholinergic nerve
  • DNA microarray
  • Helical heart
  • Myocardial infarction
  • Nerve sprouting
  • Neural regeneration
  • Neural remodeling
  • Neurotrophic factors
  • Sympathetic nerve

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Oh, Y. S., Jong, A. Y., Kim, D. T., Li, H., Wang, C., Zemljic-Harpf, A., Ross, R. S., Fishbein, M. C., Chen, P. S., & Chen, L. S. (2006). Spatial distribution of nerve sprouting after myocardial infarction in mice. Heart Rhythm, 3(6), 728-736. https://doi.org/10.1016/j.hrthm.2006.02.005