Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs.
Cardiac nerve sprouting and sympathetic hyperinnervation after myocardial infarction (MI) both contribute to arrhythmogenesis and sudden death. However, the mechanisms responsible for nerve sprouting after MI are unclear. The expression of nerve growth factor (NGF), growth associated protein 43 (GAP43), and other nerve markers were studied at the infarcted site, the noninfarcted left ventricle free wall (LVFW), and the left stellate ganglion (LSG) at several time points (30 minutes to 1 month) after MI. Transcardiac (difference between coronary sinus and aorta) NGF levels were also assayed. Acute MI resulted in the immediate elevation of the transcardiac NGF concentration within 3.5 hours after MI, followed by the upregulation of cardiac NGF and GAP43 expression, which was earlier and more pronounced at the infarcted site than the noninfarcted LVFW. However, cardiac nerve sprouting and sympathetic hyperinnervation were more pronounced in the noninfarcted than the infarcted LVFW site and peaked at 1 week after MI. The NGF and GAP43 protein levels significantly increased in the LSG from 3 days (P<0.01 for all) after MI, without a concomitant increase in mRNA. There was persistent elevation of NGF levels in aorta and coronary sinus within 1 month after MI. We conclude MI results in immediate local NGF release, followed by upregulation of NGF and GAP43 expression at the infarcted site. NGF and GAP43 are transported retrogradely to LSG, which triggers nerve sprouting at the noninfarcted LVFW. A rapid and persistent upregulation of NGF and GAP43 expression at the infarcted site underlies the mechanisms of cardiac nerve sprouting after MI.
Zhou
Shengmei
S
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif, USA.
Chen
Lan S
LS
Miyauchi
Yasushi
Y
Miyauchi
Mizuho
M
Kar
Saibal
S
Kangavari
Simon
S
Fishbein
Michael C
MC
Sharifi
Behrooz
B
Chen
Peng-Sheng
PS
D000818:Animals; D004285:Dogs; D019922:GAP-43 Protein / Q000378:metabolism; D015870:Gene Expression; D006321:Heart / Q000294:innervation*; D007700:Kinetics; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D013233:Stellate Ganglion / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology
D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D020932:Nerve Growth Factor