The investigation of the plasticity of cardiac sympathetic neurons in heart failure

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249051
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Keio University
• Principal Investigator: FUKUDA Keiichi 慶應義塾大学, 医学部, 教授 (20199227)
• Project Period (FY): 2009 – 2011
• Keywords: 神経科学 / 循環器・高血圧 / 生体分子 / 脳・神経 / 発生・分化 / 心臓 / 心不全 / 白血病抑制因子

Research Abstract

During congestive heart failure(CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system(SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. The cholinergic differentiation factors leukemia inhibitory factor(LIF) and cardiotrophin-1(CT-1) were strongly upregulated in CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.

Research Products

• [Journal Article] Development, maturation, and transdifferentiation of cardiac sympathetic nerves (2012)
  • Author(s): Kimura K, Ieda M, Fukuda K
  • Journal Title: Circ Res Volume: 110 Pages: 325-36
  • Peer Reviewed
• [Journal Article] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines (2010)
  • Author(s): Hideaki Kanazawa, Masaki Ieda, Kensuke Kimura, Takahide Arai, Haruko Kawaguchi-Manabe, Jin Endo, Takashi Kawakami, Tokuhiro Kimura, Toshiaki Monkawa, Matsuhiko Hayashi, Akio Iwanami, Hideyuki Okano, Yasunori Okada, Hatsue Ishibashi-Ueda, Satoshi Ogawa, Keiichi Fukuda
  • Journal Title: J Clin Invest Volume: 120(2) Pages: 408-21
  • Peer Reviewed
• [Journal Article] Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure (2010)
  • Author(s): Kensuke Kimura, Hideaki Kanazawa, Masaki Ieda, Haruko Kawaguchi-Manabe, Yoshiko Miyake, Takashi Yagi, Takahide Arai, Motoaki Sano, Keiichi Fukuda
  • Journal Title: Autonomic Neuroscience : Basic and Clinical Volume: 156 Pages: 27-35
  • Peer Reviewed
• [Journal Article] Cardiac innervation and sudden cardiac death (2009)
  • Author(s): Ieda M, Fukuda K
  • Journal Title: Cur r Cardiol Rev Volume: 5 Pages: 289-95
  • Peer Reviewed
• [Journal Article] Cardiac innervation and sudden cardiac death (2009)
  • Author(s): Masaki Ieda, Keiichi Fukuda
  • Journal Title: Cur rent Cardiology Review Volume: 5 Pages: 289-295
  • Peer Reviewed
• [Presentation] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines. Melvin L. Marcus Young Investigator's Award Prize (2009)
  • Author(s): Hideaki Kanazawa, Masaki Ieda, Satoshi Ogawa, and Keiichi Fukuda
  • Organizer: American Heart Association, 81th Scientific Meeting
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 20091114-17
• [Book] 医学のあゆみ特集『心不全:研究と臨床の最前線』『心不全における交感神経異常:交感神経の可塑性と新しい病態生理』 (2010)
  • Author(s): 金澤英明、福田恵一
  • Total Pages: 370-377
  • Publisher: 医歯薬出版
• [Book] 心不全における交感神経の分化転換Heart View (2010)
  • Author(s): 金澤英明、福田恵一
  • Total Pages: 60-65