Spatial distribution of nerve sprouting after myocardial infarction in mice.
BACKGROUND
Myocardial infarction (MI) elicits nerve sprouting.


OBJECTIVE
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-1alpha 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.


CONCLUSIONS
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-1alpha occurred in the peri-infarct area and, to a lesser extent, in the remote area.
Oh
Yong-Seog
YS
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90027, USA.
Jong
Ambrose Y
AY
Kim
Dave T
DT
Li
Hongmei
H
Wang
Charles
C
Zemljic-Harpf
Alice
A
Ross
Robert S
RS
Fishbein
Michael C
MC
Chen
Peng-Sheng
PS
Chen
Lan S
LS
D000818:Animals; D004562:Electrocardiography; D019922:GAP-43 Protein / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000294:innervation*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D053605:Leukemia Inhibitory Factor; D051379:Mice; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009412:Nerve Fibers / Q000378:metabolism; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D009416:Nerve Regeneration; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D013002:Somatomedins / Q000096:biosynthesis / Q000235:genetics; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D019922:GAP-43 Protein; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012333:RNA, Messenger; D013002:Somatomedins; D020932:Nerve Growth Factor