Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

Autor: Singh S; Research Services, Hines VA Medical Center, Hines, IL., Sayers S, Walter JS, Thomas D, Dieter RS, Nee LM, Wurster RD
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2013 Aug 19; Vol. 2 (4), pp. e000210. Date of Electronic Publication: 2013 Aug 19.
DOI: 10.1161/JAHA.113.000210
Abstrakt: 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.
Databáze: MEDLINE
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