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心臓のエネルギー代謝における心臓線維芽細胞と心筋細胞の相互連関

Research Project

Project/Area Number 18J23428
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Cardiovascular medicine
Research InstitutionNagoya University (2020)
Gunma University (2018-2019)

Principal Investigator

古川 希  名古屋大学, 医学系研究科, 助教

Project Period (FY) 2018-04-25 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2020: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2019: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2018: ¥800,000 (Direct Cost: ¥800,000)
Keywords心臓エネルギー代謝 / FGF21 / 心肥大 / 心不全 / エネルギー代謝 / 線維化
Outline of Annual Research Achievements

①線維芽細胞特異的FGF21欠損マウス[FB-FGF21KOマウス]:前年度よりサンプル数を重ねて、コンダクタンスカテーテルで詳細に心機能検討したところ、コントロール圧負荷群と比較し収縮期末圧容積関係や弛緩能[Tau]がFB-FGF21KOマウス群では更に増悪していた。心臓エネルギー代謝の定量の検討では、糖取り込みはコントロールの圧負荷群で有意に増加していたが、FB-FGF21KOマウスの圧負荷群と比較し更に増加傾向であることが分かった。脂肪酸取り込みはコントロール群との差は見られなかった。その他、マッソン染色による線維化定量の検討ではコントロールの圧負荷群と比較しFB-FGF21KOマウスの圧負荷群で更に増悪していることが分かった。これまでの研究成果はアメリカ心臓学会基礎研究会(BCVS)2020に採択された。②心筋細胞特異的FGF21欠損マウス[MCM-FGF21KOマウス]:前年度ではFGF21floxマウスとMCM-FGF21の圧負荷無処置・処置群の4群で比較検討したが、FGF21mflox群も加え全6群のマウスの心臓におけるRNAサンプルにて検討を行った。その結果、心ストレスや線維化マーカーのmRNA発現がMCM-FGF21KOマウス群では増悪することが分かった。③全身FGF21欠損マウス[FGF21KOマウス]:これまでのKOマウスと同様、圧負荷後に著明な収縮能の低下、拡張末期径の増悪がみられた。圧負荷1週及び3-4週後でタイムコース実験を行い急性期/慢性期のFGF21の応答を検討したところ、特に圧負荷1週で心機能が著明に低下することが明らかとなった。以上より、FGF21は病的心ストレスに対して多臓器だけでなく心臓自体からも産生され、線維芽細胞によるパラクライン作用、心筋細胞自体からのオートクライン作用によっても心臓エネルギー代謝を調節する可能性が示唆された。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] The prebiotic fiber inulin ameliorates cardiac, adipose tissue, and hepatic pathology, but exacerbates hypertriglyceridemia in rats with metabolic syndrome2021

    • Author(s)
      Komatsu Yuki、Aoyama Kiyoshi、Yoneda Mamoru、Ashikawa Sao、Nakano Shiho、Kawai Yumeno、Cui Xixi、Furukawa Nozomi、Ikeda Katsuhide、Nagata Kohzo
    • Journal Title

      American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 320 Issue: 1 Pages: H281-H295

    • DOI

      10.1152/ajpheart.00657.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism2020

    • Author(s)
      Furukawa Nozomi、Koitabashi Norimichi、Matsui Hiroki、Sunaga Hiroaki、Umbarawan Yogi、Syamsunarno Mas Rizky A. A.、Yamaguchi Aiko、Obokata Masaru、Hanaoka Hirofumi、Yokoyama Tomoyuki、Kurabayashi Masahiko
    • Journal Title

      Heart and Vessels

      Volume: 36 Issue: 1 Pages: 136-146

    • DOI

      10.1007/s00380-020-01711-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surgical ablation of whitened interscapular brown fat ameliorates cardiac pathology in salt‐loaded metabolic syndrome rats2020

    • Author(s)
      Komatsu Yuki、Aoyama Kiyoshi、Yoneda Mamoru、Ito Shogo、Sano Yusuke、Kawai Yumeno、Cui Xixi、Yamada Yuichiro、Furukawa Nozomi、Ikeda Katsuhide、Nagata Kohzo
    • Journal Title

      Annals of the New York Academy of Sciences

      Volume: 1492 Issue: 1 Pages: 11-26

    • DOI

      10.1111/nyas.14546

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension2019

    • Author(s)
      Seki Mitsuru、Furukawa Nozomi、Koitabashi Norimichi、Obokata Masaru、Conway Simon J、Arakawa Hirokazu、Kurabayashi Masahiko
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 8 Pages: e0220795-e0220795

    • DOI

      10.1371/journal.pone.0220795

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Cardiac Fibroblast and myocytes-derived FGF21 is a novel Target and their interaction plays a Pivotal role for pathological remodeling in Pressure-Overload mice.2021

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Tomoyuki Yokoyama, Kohzo Nagata, Masahiko Kurabayashi
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A hot water extract of low Curcumin Curcuma Longa ameliorates cardiac and subcutaneous fat inflammation in rats with metabolic syndrome2021

    • Author(s)
      Nozomi Furukawa, Yumeno Kawai, Xixi Cui, Kana Hirota, Hirona Mori, Yurina Ishida, Yuka Hirano, Misaki Ikei, Katsuhide Ikeda, Kohzo Nagata
    • Organizer
      第85回日本循環器学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Dietary Soy Protein Exacerbates Cardiac Hypertrophy but Ameliorates Cardiac Fibrosis and Diastolic Dysfunction in Rats with Metabolic Syndrome2021

    • Author(s)
      Xixi Cui, Yumeno Kawai, Misaki Ikei, Tomo Nishimura, Akane Nomura, Nozomi Furukawa, Katsuhide Ikeda, Kohzo Nagata
    • Organizer
      第85回日本循環器学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Sacubitril/Valsartan Improves Passive Myocardial Stiffness via Increased Titin Phosphorylation through cGMP-PKG activation2020

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      第84回日本循環器学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Deranged fatty acid composition by Elovl6-knockout induces cardioprotective mechanism during pressure overload: a Potential New Therapeutic Target for Heart Failure.2020

    • Author(s)
      Sayaka Tadaki, Hiroki Matsui, Hiroaki Sunaga, Yogi Umbarawan, Nozomi Furukawa, Norimichi Koitabashi, Tatsuya Iso, Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      第84回日本循環器学会総会・学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cardiac Fibroblast-derived FGF21 is a Novel Therapeutic Target for Cardiac Pathological Remodeling.2020

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      Basic Cardiovascular Sciences 2020 scientific sessions
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cardiac Fibroblast-driven FGF21 Regulates Cardiac Pathological Remodeling Induced by Pressure Overload.2020

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Tomoyuki Yokoyama, Mashiko Kurabayashi
    • Organizer
      第4回日本循環器学会基礎研究フォーラム
    • Related Report
      2020 Annual Research Report
  • [Presentation] DPP-4 inhibitor, Vildagliptin, Induces FGF21 in Cardiac Fibroblasts and Improves Myocardial Energy Metabolism through Upregulation of Sirt1.2019

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Hiroaki Sunaga, Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      第36回国際心臓研究学会日本部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DPP-4 inhibitor, Vildagliptin, induce FGF21 expression through AMPK-Sirt1 signaling in non-diabetic mice heart.2019

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Hiroaki Sunaga, Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      第83回日本循環器学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DPP-4 inhibitor, Vildagliptin, Induce FGF21 Expression through AMPK-Sirt1 Signaling in Non-diabetic Hypertrophied Mice Heart2019

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Hiroaki Sunaga,Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      第83回日本循環器学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Sacubitril/Valsartan Improves Passive Myocardial Stiffness in Diabetic Mice: Increased Phosphorylation in Titin2018

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroki Matsui, Yogi Umbarawan,Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      American Heart Association (AHA) Scientific Session 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sacubitril/Valsartan Improves Passive Myocardial Stiffness via increased Titin Phosphorylation in Diabetic Mice2018

    • Author(s)
      Nozomi Furukawa, Norimichi Koitabashi, Hiroaki Sunaga, Yogi Umbarawan,Tomoyuki Yokoyama, Masahiko Kurabayashi
    • Organizer
      第35回国際心臓研究学会日本部会
    • Related Report
      2018 Annual Research Report

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Published: 2018-05-01   Modified: 2024-03-26  

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