Spatial distribution of nerve sprouting after myocardial infarction in mice
Spatial distribution of nerve sprouting after myocardial infarction in mice
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DOI：
10.1016/j.hrthm.2006.02.005
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发表时间：
2006-06-01
期刊：
影响因子：
5.5
通讯作者：
Chen, Lan S.
中科院分区：
文献类型：
--
作者：
Oh, Yong-Seog;Jong, Ambrose Y.;Chen, Lan S.
背景 心肌梗塞（MI）会引起神经出芽。目的本研究的目的是确定 MI 后神经出芽的空间分布和神经营养基因表达。方法我们通过冠状动脉结扎在小鼠中产生 MI。 MI后3小时至2个月取出心脏，并使用Affymetrix微阵列和mRNA分析检查神经纤维密度和神经营养因子基因表达。结果生长相关蛋白（GAP）-43免疫阳性的神经纤维密度在梗塞周围区域和远离梗塞区域的神经纤维密度在MI后3小时最高，导致心室中交感神经（但不是副交感神经）过度神经支配。心肌的GAP-43阳性神经纤维密度在外横环中比在内垂直环中更大。这两种心肌环之间的差异在 MI 后 3 小时内达到峰值，并持续 2 个月。与正常对照组相比，神经生长因子、胰岛素样生长因子、白血病抑制因子、转化生长因子-β(3) 和白细胞介素-1 α 的基因表达在 MI 后长达 2 个月内增加。这些生长因子的表达在梗塞周围区域比在远端区域更加明显和持久。结论 MI 在梗塞周围和远端区域均诱导交感神经萌芽，尤其是在外横环中。神经生长因子、胰岛素样生长因子、白血病抑制因子、转化生长因子-β(3) 和白细胞介素-1a 的选择性上调发生在梗死周围区域，并且在偏远区域出现较小程度的上调。
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-beta(3), and interleukin-1 alpha 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-beta(3), and interleukin-la occurred in the peri-infarct area and, to a Lesser extent, in the remote area.