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Basic research for the development of innovative therapeutic approaches against heart failure

Research Project

Project/Area Number 18H02809
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKumamoto University

Principal Investigator

OIKE Yuichi  熊本大学, 大学院生命科学研究部(医), 教授 (90312321)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords心不全 / ミトコンドリア / エネルギー代謝 / ANGPTL2 / 心筋
Outline of Final Research Achievements

In this study, we showed a molecular mechanism underlying the enhancement of mitochondrial energy metabolism in cardiomyocytes by ANGPTL2 suppression. Suppressing ANGPTL2 expression in cardiomyocytes enhances mitochondrial respiratory function by increasing the respiratory chain complex II and decreases the production of reactive oxygen species. Moreover, we identified a novel lncRNA Caren and demonstrated that Caren functions in cardioprotection by enhancing mitochondrial biogenesis and inhibiting the activation of DNA damage response in cardiomyocytes. We also found that the expression level of Caren decreases in cardiomyocytes of failing heart and showed that re-expression of Caren in cardiomyocytes could be a novel therapeutic strategy against heart failure.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として、心筋細胞におけるミトコンドリアエネルギー代謝機能の改善が、心不全の新たな治療戦略として有効であることを明らかにするなど、新規治療法開発につながる重要な基盤研究となった。さらに、本研究の成果は、心筋細胞におけるミトコンドリアエネルギー代謝機能制御機構として、ANGPTL2抑制による呼吸鎖複合体IIの活性促進や新規lncRNAであるCarenによるミトコンドリア生合成促進などの作用機序の解明といった学術的意義も有する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (43 results)

All 2021 2020 2019 2018 Other

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 15 results) Book (6 results) Remarks (3 results)

  • [Journal Article] The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis.2021

    • Author(s)
      Sato M, Kadomatsu T, Miyata K, Warren SJ, Tian Z, Zhu S, Horiguchi H, Makaju A, Bakhtina A, Morinaga J, Sugizaki T, Hirashima K, Yoshinobu K, Imasaka M, Araki M, Komohara Y, Wakayama T, Nakagawa S, Franklin S, Node K, Araki K, Oike Y.
    • Journal Title

      Nat Commun

      Volume: -

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stroma-derived ANGPTL2 establishes an anti-tumor microenvironment during intestinal tumorigenesis2020

    • Author(s)
      Horiguchi Haruki、Kadomatsu Tsuyoshi、Miyata Keishi、Terada Kazutoyo、Sato Michio、Torigoe Daisuke、Morinaga Jun、Moroishi Toshiro、Oike Yuichi
    • Journal Title

      Oncogene

      Volume: 40 Issue: 1 Pages: 55-67

    • DOI

      10.1038/s41388-020-01505-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor cell-derived angiopoietin-like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells.2020

    • Author(s)
      Osumi H, Horiguchi H, Kadomatsu T, Tashiro K, Morinaga J, Takahashi T, Ikeda K, Ito T, Suzuki M, Endo M, Oike Y
    • Journal Title

      Cancer Sci

      Volume: - Issue: 4 Pages: 1241-1253

    • DOI

      10.1111/cas.14337

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.2020

    • Author(s)
      Fukami H, Morinaga J, Okadome Y, Nishiguchi Y, Iwata Y, Kanki T, Nakagawa T, Izumi Y, Kakizoe Y, Kuwabara T, Horiguchi H, Sato M, Kadomatsu T, Miyata K, Tajiri T, Oike Y, Mukoyama M.
    • Journal Title

      Atherosclerosis.

      Volume: 315 Pages: 18-23

    • DOI

      10.1016/j.atherosclerosis.2020.10.890

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice2019

    • Author(s)
      Sato M, Miyata K, Tian Z, Kadomatsu T, Ujihara Y, Morinaga J, Horiguchi H, Endo M, Zhao J, Zhu S, Sugizaki T, Igata K, Muramatsu M, Minami T, Ito T, Bianchi ME, Mohri S, Araki K, Node K, Oike Y
    • Journal Title

      Circulation Journal

      Volume: 83 Issue: 2 Pages: 368-378

    • DOI

      10.1253/circj.CJ-18-0925

    • NAID

      130007557092

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2019-01-25
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity.2019

    • Author(s)
      Horiguchi H, Kadomatsu T, Kurahashi R, Hara C, Miyata K, Baba M, Osumi H, Terada K, Araki K, Takai T, Kamba T, Linehan WM, Moroishi T & Oike Y.
    • Journal Title

      Genes Dev

      Volume: 33 Pages: 1641-1656

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aging- and obesity-related peri-muscular adipose tissue accelerates muscle atrophy2019

    • Author(s)
      Zhu Shunshun、Tian Zhe、Torigoe Daisuke、Zhao Jiabin、Xie Peiyu、Sugizaki Taichi、Sato Michio、Horiguchi Haruki、Terada Kazutoyo、Kadomatsu Tsuyoshi、Miyata Keishi、Oike Yuichi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 8 Pages: e0221366-e0221366

    • DOI

      10.1371/journal.pone.0221366

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study2019

    • Author(s)
      Morinaga J, Kakuma T, Fukami H, Hayata M, Uchimura K, Mizumoto T, Kakizoe Y, Miyoshi T, Shiraishi N, Adachi M, Izumi Y, Kuwabara T, Okadome Y, Sato M, Horiguchi H, Sugizaki T, Kadomatsu T, Miyata K, Tajiri S, Tajiri T, Tomita K, Kitamura K, Oike Y, Mukoyama M.
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: 印刷中 Issue: 5 Pages: 854-860

    • DOI

      10.1093/ndt/gfz236

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TFE3 Xp11.2 translocation renal cell carcinoma mouse model reveals novel therapeutic targets and identifies GPNMB as a diagnostic marker for human disease.2019

    • Author(s)
      Baba M, Furuya M, Motoshima T, Lang M, Funasaki S, Ma W, Sun HW, Hasumi H, Huang Y, Kato I, Kadomatsu T, Satou Y, Morris N, Karim BO, Ileva L, Kalen JD, Wilan Krisna LA, Hasumi Y, Sugiyama A, Kurahashi R, Nishimoto K, Oyama M, Nagashima Y, Kuroda N, Araki K, Eto M, Yao M, Kamba T, Suda T, Oike Y, Schmidt LS, Linehan WM
    • Journal Title

      Molecular Cancer Research

      Volume: 印刷中 Issue: 8 Pages: 1613-1626

    • DOI

      10.1158/1541-7786.mcr-18-1235

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MiR-204-5p: a novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma.2019

    • Author(s)
      Kurahashi R, Kadomatsu T, Baba M, Hara C, Itoh H, Miyata K, Endo M, Morinaga J, Terada K, Araki K, Eto M, Schmidt LS, Kamba T, Linehan WM, Oike Y.
    • Journal Title

      Cancer Science

      Volume: 印刷中 Issue: 6 Pages: 1897-1908

    • DOI

      10.1111/cas.14026

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of angiopoietin-like proteins in regulation of stem cell activity.2019

    • Author(s)
      Kadomatsu T, Oike Y.
    • Journal Title

      J. Biochem.

      Volume: 165 Issue: 4 Pages: 309-315

    • DOI

      10.1093/jb/mvz005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] keratinocytes increase melanogenesis via ANGPTL2 induction, an activity antagonized by Chrysanthemum extract.2019

    • Author(s)
      Satou G, Maji D, Isamoto T, Oike Y, Endo M
    • Journal Title

      Exp Dermatol

      Volume: 28 Issue: 2 Pages: 152-160

    • DOI

      10.1111/exd.13862

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiopoietin-Like Protein 2 Promotes the Progression of Diabetic Kidney Disease2018

    • Author(s)
      Ishii Toshihisa、Furuya Fumihiko、Takahashi Kazuya、Shikata Miho、Takamura Takeyuki、Kobayashi Hidetoshi、Miyazaki Asako、Morinaga Jun、Terada Kazutoyo、Oike Yuichi、Kanda Eiichiro、Kitamura Kenichiro
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 104 Issue: 1 Pages: 172-180

    • DOI

      10.1210/jc.2017-02705

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The IncRNA Caren Protects Against Heart Failure by Inactivating the ATM-DNA Damage Response Pathway and Activating Mitochondrial Biogenesis2021

    • Author(s)
      Sato Michio, Keishi Miyata, Yuichi Oike
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アンジオポエチン様因子による生体恒常性維持とその変容2021

    • Author(s)
      尾池 雄一
    • Organizer
      第28回日本血管生物医学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Current topics of angiopoietin-like (Angptls) research2020

    • Author(s)
      Yuichi Oike
    • 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
    • Invited
  • [Presentation] Identification of a novel cardiomyocyte-enriched long noncoding RNA counteracting against heart failure development2020

    • Author(s)
      Michio Sato, Keishi Miyata, Tsuyoshi Kadomatsu, Yuichi Oike
    • 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] 血液透析患者における血中ANGPTL2値と死亡リスクの関連2020

    • Author(s)
      佐藤迪夫、森永 潤、向山政志、尾池雄一
    • Organizer
      第20回日本抗加齢医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 心不全の分子病態解明による遺伝子治療開発研究2020

    • Author(s)
      尾池雄一
    • Organizer
      第24回日本心不全学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Intercellular communication via angiopoietin-like protein 2 signaling in the regulation of anti-tumor immunity2020

    • Author(s)
      Tsuyoshi Kadomatsu, Haruki Horiguchi, Yuichi Oike
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 健康長寿に向けた脂質異常症治療におけるゲノム診療の役割2020

    • Author(s)
      尾池 雄一
    • Organizer
      第2回日本抗加齢医学会 九州地方会 学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ANGPTL2: a causal player in accelerating heart disease development in the aging2020

    • Author(s)
      Yuichi Oike
    • Organizer
      The 4th Annual International Hawaii Cardiovascular Symposium (2020IHCVS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of a novel cytoplasmic long noncoding RNA protecting against heart failure2020

    • Author(s)
      Yuichi Oike
    • Organizer
      2020 Keystone Symposia Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小児期から考える健康長寿に向けた脂質異常症治療戦略と展望2019

    • Author(s)
      尾池 雄一
    • Organizer
      第33回日本小児脂質研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The long noncoding RNA Caren protects against heart failure in mice2019

    • Author(s)
      Michio Sato, Keishi Miyata, Tsuyoshi Kadomatsu, Koichi Node, Yuichi Oike
    • Organizer
      第3回日本循環器学会基礎研究フォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] A Novel IncRNA Protects from Pressure Overload Induced Heart Failure in Mice2019

    • Author(s)
      Yuichi Oike
    • Organizer
      Basic Cardiovascular Sciences 2019 Scientific Sessions
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心不全の薬物療法の現状と新たな治療法の可能性2019

    • Author(s)
      尾池 雄一
    • Organizer
      第25回日本遺伝子細胞治療学会学術集会(JSGCT2019)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 心血管疾患と代謝・生活習慣病におけるANGPTL2の役割2019

    • Author(s)
      尾池 雄一
    • Organizer
      第51回日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Loss of HMGB2 Exacerbate Pressure Overload-induced Heart Failure in Mice2019

    • Author(s)
      佐藤 迪夫、田 哲、宮田 敬士、野出 孝一、尾池 雄一
    • Organizer
      第83回日本循環器学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 加齢関連疾患促進タンパク質ANGPTL2を抑制する機能性素材の探索の試み2018

    • Author(s)
      尾池雄一
    • Organizer
      脳心血管抗加齢研究会2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 加齢関連疾患の分子解明を目指したモデル動物研究の実践2018

    • Author(s)
      尾池雄一
    • Organizer
      第54回高血圧関連疾患モデル学会 学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 動脈硬化性疾患とアンジオポエチン様因子2018

    • Author(s)
      尾池雄一
    • Organizer
      第50回日本動脈硬化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Identification of candidate genes for gene therapy against heart failure2018

    • Author(s)
      尾池雄一
    • Organizer
      第24回日本遺伝子細胞治療学会(JSGCT2018)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 心不全の分子基盤解明と治療戦略2018

    • Author(s)
      尾池雄一
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 循環器内科2020

    • Author(s)
      門松 毅、尾池雄一
    • Publisher
      科学評論社
    • Related Report
      2020 Annual Research Report
  • [Book] 日本体質医学会雑誌2019

    • Author(s)
      尾池 雄一
    • Publisher
      日本体質医学会
    • Related Report
      2019 Annual Research Report
  • [Book] 週間 医学のあゆみ 特集:動脈硬化UPDATE2019

    • Author(s)
      尾池 雄一
    • Publisher
      医歯薬出版
    • Related Report
      2019 Annual Research Report
  • [Book] 別冊・医学のあゆみ 動脈硬化 UPDATE2019

    • Author(s)
      尾池 雄一
    • Publisher
      医歯薬出版
    • Related Report
      2019 Annual Research Report
  • [Book] 週間 医学のあゆみ 特集:動脈硬化UPDATE2019

    • Author(s)
      尾池雄一
    • Total Pages
      120
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2018 Annual Research Report
  • [Book] 別冊 BIO Clinica 慢性炎症と疾患 心臓と血管の慢性炎症(生活習慣病)102018

    • Author(s)
      門松 毅、尾池雄一
    • Total Pages
      170
    • Publisher
      北隆館
    • Related Report
      2018 Annual Research Report
  • [Remarks] 熊本大学大学院生命科学研究部 分子遺伝学講座

    • URL

      http://www.kumamoto-u-molgene.jp

    • Related Report
      2020 Annual Research Report
  • [Remarks] 熊本大学大学院生命科学研究部 分子遺伝学講座

    • URL

      http://www.kumamoto-u-molgene.jp

    • Related Report
      2019 Annual Research Report
  • [Remarks] 熊本大学 大学院生命科学研究部 分子遺伝学講座

    • URL

      http://www.kumamoto-u-molgene.jp

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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