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Elucidation of molecular mechanism of stress-induced cardiomyopathy through brain-heart interaction.

Research Project

Project/Area Number 25670395
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionKeio University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) ARAI Takahide  慶應義塾大学, 医学部, 講師(非常勤) (00383894)
KANAZAWA Hideaki  慶應義塾大学, 医学部, 特任講師 (40338033)
SUKEGAWA Hiroaki  慶應義塾大学, 医学部, 助教 (60535607)
TABEI Ryota  慶應義塾大学, 医学部, 助教 (20573322)
MUNAKATA Masahito  慶應義塾大学, 医学部, 共同研究員 (40445284)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywordsストレス / 脳 / サイトカイン / 脳心連関 / 炎症 / 臓器連関
Outline of Final Research Achievements

Major emotional stress may induce stress cardiomyopathy (SC), although the precise molecular mechanisms remain unclear. Using an animal model of SC, we first located the central cardiac sympathetic nerves (CSNs) in the hypothalamus innervating the left ventricular (LV) apex, and then investigated the gene expression changes in these regions. We found that chemokine ligand 2 (Ccl2), produced by activated astrocytes, strongly stimulated the central CSNs. The subsequent sympathetic activation upregulated neuropeptide Y (NPY) expression in both the stellate ganglion (SG) and CSNs. NPY in turn had a negative inotropic effect and strongly blocked -adrenergic stimulation. Thus, administration of Ccl2 into the central neurons evoked SC and increased NPY at the SG. Moreover, siRNA downregulation of NPY in the SG completely abrogated the induced SC. Overall, our results provide to explain how emotional stress affects molecular signals in the brain, leading to LV apical ballooning.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] A massive floating culture system with metabolic purification for human induced pluripotent stem cell-derived cardiomyocytes.2014

    • Author(s)
      Natsuko Hemmi, Shugo Tohyama, Kazuaki Nakajima, Hideaki Kanazawa, Tomohisa Seki, Yoshikazu Kishino, Akinori Hirano, Marina Okada, Ryota Tabei, Rei Ohno, Chihana Fujita, Fumiyuki Hattori, Shinsuke Yuasa, Motoaki Sano, Jun Fujita, and Keiichi Fukuda.
    • Journal Title

      Stem Cells Translational Medicine.

      Volume: 3 Pages: 1473-1483

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Derivation of Transgene-free Human Induced Pluripotent Stem Cells from Human Peripheral T Cells in Defined Culture Conditions.2014

    • Author(s)
      Yoshikazu Kishino, Tomohisa Seki, Jun Fujita, Shinsuke Yuasa, Shugo Tohyama, Akira Kunitomi, Ryota Tabei, Kazuaki Nakajima, Marina Okada, Akinori Hirano, Hideaki Kanazawa, Keiichi Fukuda.
    • Journal Title

      PLoS One.

      Volume: 9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Distinct Metabolic Flow Enables Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes.2013

    • Author(s)
      Tohyama S, Hattori F, Sano M, Hishiki T, Nagahata Y, Matsuura T, Hashimoto H, Suzuki T, Yamashita H, Satoh Y, Egashira T, Seki T, Muraoka N, Yamakawa H, Ohgino Y, Tanaka T, Yoichi M, Yuasa S, Murata M, Suematsu M, Fukuda K.
    • Journal Title

      Cell Stem Cell

      Volume: 12 Pages: 127-137

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Disparity in the application of guideline-based medical therapy after percutaneous coronary intervention: analysis from the Japanese prospective multicenter registry.2013

    • Author(s)
      Endo A, Kohsaka S, Miyata H, Kawamura A, Noma S, Suzuki M, Koyama T, Ishikawa S, Momiyama Y, Nakagawa S, Sueyoshi K, Takagi S, Takahashi T, Sato Y, Ogawa S, Fukuda K.
    • Journal Title

      Am J Cardiovasc Drugs.

      Volume: 13 Pages: 103-12

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic value of portable electrocardiogram (Cardiophone) in patients complaining of palpitation.2013

    • Author(s)
      Aizawa Y, Takatsuki S, Suenaga Y, Kimura T, Nishiyama N, Fukumoto K, Tanimoto Y, Tanimoto K, Kohsaka S, Fukuda Y, Murata M, Miyoshi S, Sato T, Iwanaga S, Ogawa S, Fukuda K.
    • Journal Title

      Int J Cardiol.

      Volume: 168(3) Pages: 2925-7

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction.2013

    • Author(s)
      Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, Yamamoto T, Takeshima A, Shinmura K, Shen W, Fukuda K, Sano M.
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 62 Pages: 24-35

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anatomical variations affect radial artery spasm and procedural achievement of transradial cardiac catheterization.2013

    • Author(s)
      Numasawa Y, Kawamura A, Kohsaka S, Takahashi M, Endo A, Arai T, Ohno Y, Yuasa S, Maekawa Y, Fukuda K.
    • Journal Title

      Heart Vessels.

      Volume: 29 Pages: 49-57

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 心臓交感神経から心臓病を診る2014

    • Author(s)
      金澤英明、木村謙介、荒井隆秀、福田恵一
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      九州大学医学部百年講堂
    • Year and Date
      2014-07-04 – 2014-07-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 心不全における心臓交感神経の適応機構2014

    • Author(s)
      金澤英明、木村謙介、荒井隆秀、家田真樹、福田恵一
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 『iPS細胞の循環器病学への臨床応用』2013

    • Author(s)
      福田恵一
    • Organizer
      第105回ACCP日本部会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 『iPS細胞の循環器領域への臨床応用』2013

    • Author(s)
      福田恵一
    • Organizer
      第24回心エコ-図学会特別講演
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] 循環制御2014

    • Author(s)
      金澤英明、木村謙介、荒井隆秀、福田恵一
    • Publisher
      小玉株式会社出版部
    • Related Report
      2014 Annual Research Report
  • [Book] 臨床神経科学Clinical Neuroscience2014

    • Author(s)
      金澤英明、福田恵一
    • Publisher
      中外医学社
    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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