Arrhythmogenic gene change and nerve sprouting after acute myocardial infarction in mice

Yong Seog Oh, Ji Hoon Kim, Yun Seok Choi, Ha Wook Park, Dong Hyoen Lee, Woo Seung Shin, Ho Joong Youn, Man Young Lee, Wook Sung Chung, Tae Ho Rho, Jae Hyung Kim, Peng Sheng Chen, Kyu Bo Choi

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1 Scopus citations

Abstract

Background and Objectives : Myocardial infarction (MI) elicits nerve sprouting. However, the time course and spatial distribution of this nerve sprouting and its relationship to the expression of neurotrophic factors is unclear. The aim of this study was to identify the association of nerve sprouting with the expression of neurotrophic factors. Materials and Methods : We induced MI in FVB mice by ligating the left coronary artery. The hearts were removed at 3 hours to 13 months after MI for growth associated protein 43 (GAP-43) immunostaining. The nerve density (μm2/mm2) was determined by ImagePro software. In another group of mice, their myocardial tissues were processed and analyzed with using an Affymetrix RG U74V2 array. Results : The density of the nerve fibers that were immunopositive for GAP-43 was the highest 3 hours after MI in both the peri-infarct areas and the remote areas. The outer loop of the ventricle had a higher nerve density than that in the inner loop of the ventricle. The differences were at a peak 3 hours after MI, but they persisted for 2 months afterwards. The expressions of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-β3 and interleukin-1 α were increased for up to 2 months after MI as compared to the normal control. qRT PCR analyses showed increased mRNA for tyrosine hydroxylase, synaptophysin, nerve growth factor and leukemia inhibiting factor in the peri-infarct areas for up to 2 months after MI, but this occurred only for roughly 3 days after MI in the remote areas. Conclusion : We conclude that MI resulted in immediate upregulation of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-β3 and interleukin-1 α in the peri-infarct areas and this all occurred to a lesser extent in the remote areas. These changes persisted for at least 2 months, and they were associated with increased nerve sprouting activity, which was most active in the outer loop of the heart.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalKorean Circulation Journal
Volume37
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • DNA
  • Electrophysiology
  • Regeneration
  • Ventricular remodeling

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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    Oh, Y. S., Kim, J. H., Choi, Y. S., Park, H. W., Lee, D. H., Shin, W. S., Youn, H. J., Lee, M. Y., Chung, W. S., Rho, T. H., Kim, J. H., Chen, P. S., & Choi, K. B. (2007). Arrhythmogenic gene change and nerve sprouting after acute myocardial infarction in mice. Korean Circulation Journal, 37(9), 399-407. https://doi.org/10.4070/kcj.2007.37.9.399