title: Neural crest-derived resident cardiac cells contribute to the restoration of adrenergic function of transplanted heart in rodent.
abstract: OBJECTIVE
  We investigated whether neural crest-derived cardiac resident cells contribute to the restoration of intrinsic adrenergic function following transplantation in mice. Transplanted heart shows partial restoration of cardiac adrenergic activity with time. Both the intrinsic cardiac adrenergic system and extrinsic sympathetic re-innervation contribute to neuronal remodelling in the transplanted heart. Little is known about the origin and function of the intrinsic system in the transplanted heart.
  
  
  RESULTS
  Heart from the protein 0-Cre/Floxed-Enhanced Green Fluorescent Protein double-transgenic mouse was transplanted onto the abdominal aorta of the non-obese diabetic/severe combined immunodeficient mouse to trace the fate of cardiac resident neural crest-derived cells. Sympathetic nerve fibres, which are predominantly localized to the epicardial surface of the heart, disappeared in the transplanted heart. Intramyocardial neural crest cells increased immediately, while neural crest-derived nucleated tyrosine hydroxylase (TH)-immunoreactive cells increased over 2 weeks following transplantation. The mRNA expression levels of TH, dopamine-β-hydroxylase and phenylethanolamine N-methyltransferase, and the tissue content of catecholamines in the transplanted hearts increased with time in association with an increase in the number of neural crest-derived nucleated TH-immunoreactive cells and tissue nerve growth factor levels. Iodine-123-metaiodobenzylguanidine scintigraphy showed that the uptake ability of transplanted heart for catecholamines also recovered with time. Finally, the chronotropic response to tyramine both in vivo and ex vivo reappeared 2 weeks after transplantation.
  
  
  CONCLUSIONS
  Neural crest-derived adrenergic cells increased following heart transplantation. The restoration of cardiac sympathetic activities in transplanted heart is tightly coupled with an increase in the number of neural crest-derived adrenergic cells.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Université Paris-Sud, AP-HP, Service de Pneumologie, Hôpital Bicêtre, Inserm U999, Le Kremlin Bicêtre, France International University of Health and Welfare, Mita Hospital, Tokyo, Japan u1@ta-mu.net.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.affiliation: Department of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shinmura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ieda
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
authors.affiliation: FUJIFILM RI Pharma Co., Ltd, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: International University of Health and Welfare, Mita Hospital, Tokyo, Japan.
authors.forename: Satohi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Cardiology, Saitama Medical University, International Medical Center, Saitama, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakano
authors.affiliation: Department of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D016027:Heart Transplantation / Q000379:methods; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology*; D009638:Norepinephrine / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine
keywords: Regeneration; Sympathetic activity; Transplantation