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Development, maturation, and transdifferentiation of cardiac sympathetic nerves.
MedLine Citation:
PMID:  22267838     Owner:  NLM     Status:  In-Data-Review    
The heart is electrically and mechanically controlled as a syncytium by the autonomic nervous system. The cardiac nervous system comprises the sympathetic, parasympathetic, and sensory nervous systems that together regulate heart function on demand. Sympathetic electric activation was initially considered the main regulator of cardiac function; however, modern molecular biotechnological approaches have provided a new dimension to our understanding of the mechanisms controlling the cardiac nervous system. The heart is extensively innervated, although the innervation density is not uniform within the heart, being high in the subepicardium and the special conduction system. We and others showed previously that the balance between neural chemoattractants and chemorepellents determine cardiac nervous development, with both factors expressed in heart. Nerve growth factor is a potent chemoattractant synthesized by cardiomyocytes, whereas Sema3a is a neural chemorepellent expressed specifically in the subendocardium. Disruption of this well-organized molecular balance and innervation density can induce sudden cardiac death due to lethal arrhythmias. In diseased hearts, various causes and mechanisms underlie cardiac sympathetic abnormalities, although their detailed pathology and significance remain contentious. We reported that cardiac sympathetic rejuvenation occurs in cardiac hypertrophy and, moreover, interleukin-6 cytokines secreted from the failing myocardium induce cholinergic transdifferentiation of the cardiac sympathetic system via a gp130 signaling pathway, affecting cardiac performance and prognosis. In this review, we summarize the molecular mechanisms involved in sympathetic development, maturation, and transdifferentiation, and propose their investigation as new therapeutic targets for heart disease.
Kensuke Kimura; Masaki Ieda; Keiichi Fukuda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  325-36     Citation Subset:  IM    
Division of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan (; or Keiichi Fukuda, MD, PhD, Division of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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