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KMID : 0368120070370090399
Korean Circulation Journal
2007 Volume.37 No. 9 p.399 ~ p.407
Arrhythmogenic Gene Change and Nerve Sprouting after Acute Myocardial Infarction in Mice
Oh Yong-Seog

Kim Ji-Hoon
Choi Yun-Seok
Park Ha-Wook
Lee Dong-Hyoen
Shin Woo-Seung
Youn Ho-Joong
Lee Man-Young
Chung Wook-Sung
Rho Tae-Ho
Kim Jae-Hyung
Chen Peng-Sheng
Choi Kyu-Bo
Abstract
Background and Objectives£ºMyocardial 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£ºWe 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 (¥ìm2/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£ºThe 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-¥â3 and interleukin-1¥á 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£ºWe conclude that MI resulted in immediate upregulation of nerve growth factor, insulin-like growth factor, leukemia inhibitory factor, transforming growth factor-¥â3 and interleukin-1¥á 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
KEYWORD
Electrophysiology, Ventricular remodeling, Regeneration, DNA.
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