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

Research Project

Project/Area Number 21249051
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKeio University

Principal Investigator

FUKUDA Keiichi  慶應義塾大学, 医学部, 教授 (20199227)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥46,150,000 (Direct Cost: ¥35,500,000、Indirect Cost: ¥10,650,000)
Fiscal Year 2011: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2010: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2009: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
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 / LIF(白血病抑制因子) / 循環器 / 高血圧 / 発生分化 / 交感神経
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.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (29 results)

All 2012 2011 2010 2009

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (7 results) Book (3 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Development, maturation, and transdifferentiation of cardiac sympathetic nerves2012

    • Author(s)
      Kimura K, Ieda M, Fukuda K
    • Journal Title

      Circ Res

      Volume: 110 Pages: 325-36

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development, maturation, andtransdifferentiation of cardiac sympathetic nerves2012

    • Author(s)
      Kimura K, Fukuda K, et al
    • Journal Title

      Circ Res

      Volume: 110 Pages: 325-36

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory Role of Dendritic Cells in Post-Infarction Healing and Left Ventricular Remodeling2012

    • Author(s)
      Anzai A, Fukuda K, et al
    • Journal Title

      Circulation

      Volume: 125(10) Issue: 10 Pages: 1234-1245

    • DOI

      10.1161/circulationaha.111.052126

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical benefit of statin pretreatment in patients undergoing percutaneous coronary intervention : a collaborative patient-level meta-analysis of 13 randomized studies2011

    • Author(s)
      Patti G, Kinoshita M, Fukuda K, et al
    • Journal Title

      Circulation

      Volume: 123 Pages: 1622-32

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation2011

    • Author(s)
      Hara M, Fukuda K, et al
    • Journal Title

      J Exp Med

      Volume: 208 Pages: 715-27

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle2011

    • Author(s)
      Shimizu N, Fnkuda K, et al
    • Journal Title

      Cell Metab

      Volume: 13 Pages: 170-82

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines2010

    • 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

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure2010

    • 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

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines.2010

    • Author(s)
      Hideaki Kanazawa, Keiichi Fukuda, et al.
    • Journal Title

      J Clin Invest

      Volume: 120(2) Pages: 408-21

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nongenetic method for purifying stem cell-derived cardiomyocytes.2010

    • Author(s)
      Fumiyuki Hattori, Keiichi Fukuda, et al.
    • Journal Title

      Nature Methods

      Volume: 7 Pages: 61-66

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Too friable to treat?2010

    • Author(s)
      Kensuke Kimura, Keiichi Fukuda, et al.
    • Journal Title

      Lancet

      Volume: 375 Pages: 1578-1578

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] G-CSF promotes the proliferation of developing cardiomyocytes in vivo and in derivation from ES and iPS cells.2010

    • Author(s)
      Kenichiro Shimoji, Keiichi Fukuda, et al.
    • Journal Title

      Cell Stem Cell

      Volume: 6 Pages: 227-237

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells.2010

    • Author(s)
      Tomohisa Seki, Keiichi Fukuda, et al.
    • Journal Title

      Cell Stem Cell

      Volume: 7 Pages: 4-11

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents.2010

    • Author(s)
      Hakuno D, Fukuda K, et al.
    • Journal Title

      J Clin Invest

      Volume: 120 Pages: 2292-306

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines2010

    • Author(s)
      金澤英明, 福田恵一, et al.
    • Journal Title

      J Clin Invest. 120

      Pages: 408-421

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 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
    • Journal Title

      医学のあゆみ特集『心不全:研究と臨床の最前線』医歯薬出版 232

      Pages: 370-377

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Cardiac innervation and sudden cardiac death2009

    • Author(s)
      Ieda M, Fukuda K
    • Journal Title

      Cur r Cardiol Rev

      Volume: 5 Pages: 289-95

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac innervation and sudden cardiac death2009

    • Author(s)
      Masaki Ieda, Keiichi Fukuda
    • Journal Title

      Cur rent Cardiology Review

      Volume: 5 Pages: 289-295

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] iPS細胞を用いた心臓の再生と心臓病の病態解明2012

    • Author(s)
      福田恵一
    • Organizer
      第46回日本成人生活習慣病学会
    • Place of Presentation
      日本都市センターホテル(東京都)(招待講演)
    • Year and Date
      2012-01-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] iPS細胞を用いた心臓病の病態解明と難治性心不全の治療戦略2011

    • Author(s)
      福田恵一
    • Organizer
      第20回日本形成外科学会基礎学術集会特別講演
    • Place of Presentation
      ハイアットリージェンシー東京(東京都)(招待講演)
    • Year and Date
      2011-10-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] iPS細胞を用いた心不全治療の未来と心臓病の病態解明2011

    • Author(s)
      福田恵一
    • Organizer
      第97回日本消化器病病学会
    • Place of Presentation
      京王プラザホテル(東京都)(招待講演)
    • Year and Date
      2011-05-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] iPS細胞を用いた心臓病の病態解明と難治性心不全に対する治療戦略2011

    • Author(s)
      福田恵一
    • Organizer
      第84回日本内分泌学会ミニシンポジウム内分泌代謝疾患と再生医療
    • Place of Presentation
      神戸国際会議場(兵庫県)(招待講演)
    • Year and Date
      2011-04-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] iPS細胞を用いた心筋再生:from bench to bedside2011

    • Author(s)
      福田恵一
    • Organizer
      第28回日本医学会総会教育講演
    • Place of Presentation
      東京国際フォーラム(東京都)(招待講演)
    • Year and Date
      2011-04-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines. Melvin L. Marcus Young Investigator's Award Prize2009

    • Author(s)
      Hideaki Kanazawa, Masaki Ieda, Satoshi Ogawa, and Keiichi Fukuda
    • Organizer
      American Heart Association, 81th Scientific Meeting
    • Place of Presentation
      Orlando, FL, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-mediated cytokines2009

    • Author(s)
      Hideaki Kanazawa, Masaki Ieda, Keiichi Fukuda
    • Organizer
      American Heart Association, 81^<th> Scientific Meeting
    • Place of Presentation
      Orlando, FL, USA.
    • Related Report
      2009 Annual Research Report
  • [Book] Annual Review2011循環器:心不全における自律神経の適応機構2011

    • Author(s)
      金澤英明、福田恵一
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2011 Annual Research Report
  • [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
    • Publisher
      医歯薬出版
    • Related Report
      2011 Final Research Report
  • [Book] 心不全における交感神経の分化転換Heart View2010

    • Author(s)
      金澤英明、福田恵一
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 心不全の治療剤2009

    • Inventor(s)
      福田恵一
    • Industrial Property Rights Holder
      福田恵一
    • Industrial Property Number
      2008-218339
    • Filing Date
      2009-08-21
    • Related Report
      2009 Annual Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2016-04-21  

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