Abstract 16277: Neural Crest-Derived Intrinsic Cardiac Adrenergic Cells Contribute to the Restoration of Adrenergic Function of Transplanted Heart in Rodent
Background: Transplanted heart shows partial restoration of cardiac adrenergic activity with time; however, the presence of sympathetic re-innervation remains controversial. Intrinsic cardiac adrenergic (ICA) cells, which contain catecholamine-synthesizing enzymes sufficient to produce biologically active catecholamine levels, were proposed as an alternative mechanism underlying the reconstruction of cardiac adrenergic activity in transplanted heart, although little is known about the origin and roles of these ICA cells.
Methods and Results: Using genetically tagged cell derived from neural crest, we showed for the first time that ICA cells originate from neural crest-derived (NC) cells and that the restoration of cardiac sympathetic activities in transplanted heart is tightly coupled with an increase in the number of ICA cells. Sympathetic nerve fibers, which are predominantly localized to the epicardial surface of the heart, disappeared in the transplanted heart. At the same time, intramyocardial NC cells immediately increased, while ICA cells increased over 2 weeks following the transplantation. The mRNA expression levels of tyrosine hydroxylase, dopamine-β-hydroxylase, and phenylethanolamine N-methyltransferase, and the tissue content of catecholamines in the transplanted hearts increased with time. Moreover, iodine-123-MIBG scintigraphy showed that the uptake ability for catecholamines by transplanted heart also recovered with time. Finally, the chronotropic response to tyramine both in vivo and ex vivo reappeared 2 weeks after transplantation.
Conclusions: ICA cells contribute to restoring the adrenergic activities of transplanted heart in mice. NC stem cell proliferation followed by differentiation into ICA cells may contribute to an increased number of ICA cells.
- © 2012 by American Heart Association, Inc.