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Establishment of a novel therapeutic strategy for heart failure based on an understanding of metabolic regulation

Research Project

Project/Area Number 15K09081
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKobe University

Principal Investigator

Tanaka Hidekazu  神戸大学, 医学研究科, 講師 (20590342)

Co-Investigator(Kenkyū-buntansha) 杜 隆嗣  神戸大学, 医学研究科, 特命准教授 (50379418)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords心不全 / メタボローム解析 / βヒドロキシ酪酸 / 2-アミノ酪酸 / グルタチオン / 糖尿病 / 肥満 / 左室拡張能 / 心エコー図 / 抗がん剤
Outline of Final Research Achievements

1) A comprehensive quantification of serum metabolites in patients with atrial septal defect revealed that circulating levels of β-hydroxybutyrate (βOHB) and 2-aminobutyric acid (2-AB) reflected hemodynamic changes. We found that βOHB exert cardioprotective effects against oxidative stress. We also revealed that 2-AB modulates glutathione homeostasis. 2) Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. We revealed the impact of overweight on LV longitudinal myocardial systolic function in patients with type II DM.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Impact of overweight on left ventricular function in type 2 diabetes mellitus2017

    • Author(s)
      Suto Makiko、Tanaka Hidekazu、Mochizuki Yasuhide、Mukai Jun、Takada Hiroki、Soga Fumitaka、Dokuni Kumiko、Hatani Yutaka、Hatazawa Keiko、Matsuzoe Hiroki、Sano Hiroyuki、Shimoura Hiroyuki、Ooka Junichi、Matsumoto Kensuke、Hirota Yushi、Ogawa Wataru、Hirata Ken-ichi
    • Journal Title

      Cardiovascular Diabetology

      Volume: 16 Issue: 1 Pages: 145-145

    • DOI

      10.1186/s12933-017-0632-5

    • NAID

      120006373805

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2-Aminobutyric acid modulates glutathione homeostasis in the myocardium.2016

    • Author(s)
      Irino Y, Toh R, Nagao M, Mori T, Honjo T, Shinohara M, Tsuda S, Nakajima H, Satomi-Kobayashi S, Shinke T, Tanaka H, Ishida T, Miyata O, Hirata KI.
    • Journal Title

      Sci Rep.

      Volume: - Issue: 1 Pages: 36749-36749

    • DOI

      10.1038/srep36749

    • NAID

      120005898711

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bi-ventricular contractile reserve offers an incremental prognostic value for patients with dilated cardiomyopathy.2015

    • Author(s)
      Matsumoto K, Tanaka H, Onishi A, Motoji Y, Tatsumi K, Sawa T, Miyoshi T, Imanishi J, Mochizuki Y, Hirata K.
    • Journal Title

      Eur Heart J Cardiovasc Imaging.

      Volume: 16 Issue: 11 Pages: 1213-1223

    • DOI

      10.1093/ehjci/jev069

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features of subclinical left ventricular systolic dysfunction in patients with diabetes mellitus.2015

    • Author(s)
      Mochizuki Y, Tanaka H, Matsumoto K, Sano H, Toki H, Shimoura H, Ooka J, Sawa T, Motoji Y, Ryo K, Hirota Y, Ogawa W, Hirata K.
    • Journal Title

      Cardiovasc Diabetol.

      Volume: 14 Issue: 1 Pages: 37-37

    • DOI

      10.1186/s12933-015-0201-8

    • NAID

      120005647287

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combining passive leg-lifting with transmural myocardial strain profile for enhanced predictive capability for subclinical left ventricular dysfunction in Duchenne muscular dystrophy.2015

    • Author(s)
      Yamamoto T, Tanaka H, Takeshima Y, Hayashi N, Hirata K, Kawano S.
    • Journal Title

      J Cardiol.

      Volume: 66 Issue: 3 Pages: 212-217

    • DOI

      10.1016/j.jjcc.2015.02.003

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of peripheral nerve conduction in diabetic neuropathy with subclinical left ventricular systolic dysfunction.2015

    • Author(s)
      Mochizuki Y, Tanaka H, Matsumoto K, Sano H, Toki H, Shimoura H, Ooka J, Sawa T, Motoji Y, Ryo K, Hirota Y, Ogawa W, Hirata K.
    • Journal Title

      Cardiovasc Diabetol.

      Volume: 14 Issue: 1 Pages: 47-47

    • DOI

      10.1186/s12933-015-0213-4

    • NAID

      120005627300

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Right ventricular function and right-heart echocardiographic response to therapy predict long-term outcome in patients with pulmonary hypertension.2015

    • Author(s)
      Sano H, Tanaka H, Motoji Y, Fukuda Y, Sawa T, Mochizuki Y, Ryo K, Matsumoto K, Emoto N, Hirata K.
    • Journal Title

      Can J Cardiol.

      Volume: 31 Issue: 4 Pages: 529-536

    • DOI

      10.1016/j.cjca.2015.01.027

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 2-aminobutyric acid as a newly identified modulator of glutathione homeostasis in failing myocardium2017

    • Author(s)
      Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Hidekazu Tanaka, Toshiro Shinke, Tatsuro Ishida, Ken-ichi Hirata
    • Organizer
      第81回 日本循環器学会 学術集会
    • Place of Presentation
      金沢 日本
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Elevated beta-hydroxybutyrate due to downregulation of SCOT exerts cardioprotective effects in failing hearts2016

    • Author(s)
      Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Takeshige Mori, Tomoyuki Honjo, Seimi Satomi-Kobayashi, Toshiro Shinke, Hidekazu Tanaka, Tatsuro Ishida, and Ken-ichi Hirata
    • Organizer
      第80回 日本循環器学会 学術集会
    • Place of Presentation
      仙台 日本
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 2-Aminobutyric acid reflects myocardial redox state in doxorubicin-induced cardiomyopathy2015

    • Author(s)
      Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Takeshige Mori, Tomoyuki Honjo, Seimi Satomi-Kobayashi, Masakazu Shinohara, Toshiro Shinke, Tatsuro Ishida, Ken-ichi Hirata
    • Organizer
      11th International Conference of the Metabolomics Society (Metabolomics 2015)
    • Place of Presentation
      サンフランシスコ 米国
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Feasibility of 2-Aminobutyric acid as a biomarker for early detection of doxorubicin-induced cardiotoxicity2015

    • Author(s)
      Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Takeshige Mori, Tomoyuki Honjo, Seimi Satomi-Kobayashi, Masakazu Shinohara, Toshiro Shinke, Tatsuro Ishida, Ken-ichi Hirata
    • Organizer
      第79回 日本循環器学会 学術集会
    • Place of Presentation
      大阪 日本
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 抗酸化誘導剤および抗酸化誘導剤を併用する主治療薬のスクリーニング方法2016

    • Inventor(s)
      杜 隆嗣、入野 康宏、平田 健一
    • Industrial Property Rights Holder
      杜 隆嗣、入野 康宏、平田 健一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-136751
    • Filing Date
      2016-07-11
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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