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Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

BACKGROUND: Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that...

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Autores principales: Singh, Sanjay, Sayers, Scott, Walter, James S., Thomas, Donald, Dieter, Robert S., Nee, Lisa M., Wurster, Robert D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828807/
https://www.ncbi.nlm.nih.gov/pubmed/23959444
http://dx.doi.org/10.1161/JAHA.113.000210
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author Singh, Sanjay
Sayers, Scott
Walter, James S.
Thomas, Donald
Dieter, Robert S.
Nee, Lisa M.
Wurster, Robert D.
author_facet Singh, Sanjay
Sayers, Scott
Walter, James S.
Thomas, Donald
Dieter, Robert S.
Nee, Lisa M.
Wurster, Robert D.
author_sort Singh, Sanjay
collection PubMed
description BACKGROUND: Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. METHODS AND RESULTS: Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); P<0.01) and canine hearts (767.80±18.37 versus 650.23±9.84 μm(2); P<0.01) failing secondary to ischemia and neurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); P<0.01) failing secondary to hypertension reveal significant hypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. CONCLUSIONS: Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.
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spelling pubmed-38288072013-11-19 Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor Singh, Sanjay Sayers, Scott Walter, James S. Thomas, Donald Dieter, Robert S. Nee, Lisa M. Wurster, Robert D. J Am Heart Assoc Original Research BACKGROUND: Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. METHODS AND RESULTS: Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); P<0.01) and canine hearts (767.80±18.37 versus 650.23±9.84 μm(2); P<0.01) failing secondary to ischemia and neurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); P<0.01) failing secondary to hypertension reveal significant hypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. CONCLUSIONS: Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia. Blackwell Publishing Ltd 2013-08-23 /pmc/articles/PMC3828807/ /pubmed/23959444 http://dx.doi.org/10.1161/JAHA.113.000210 Text en © 2013 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley-Blackwell. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article under the terms of the Creative Commons Attribution Noncommercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Singh, Sanjay
Sayers, Scott
Walter, James S.
Thomas, Donald
Dieter, Robert S.
Nee, Lisa M.
Wurster, Robert D.
Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor
title Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor
title_full Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor
title_fullStr Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor
title_full_unstemmed Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor
title_short Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor
title_sort hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828807/
https://www.ncbi.nlm.nih.gov/pubmed/23959444
http://dx.doi.org/10.1161/JAHA.113.000210
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