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Elucidation of the mechanism of heart failure improvement effect by SGLT2 inhibitor and development of new heart failure treatment

Research Project

Project/Area Number 18K08052
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionMeiji University of Integrative Medicine

Principal Investigator

Hiroshi Asanuma  明治国際医療大学, 臨床医学講座, 教授 (20416217)

Co-Investigator(Kenkyū-buntansha) 高濱 博幸  国立研究開発法人国立循環器病研究センター, 病院, 医長 (10570301)
北風 政史  国立研究開発法人国立循環器病研究センター, 病院, 客員研究員 (20294069)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords心不全 / 薬物治療 / トランスレーショナル研究 / ドラッグリポジショニング
Outline of Final Research Achievements

Dapagliflozin, an inhibitor of SGLT2, has been reported to reduce the risk of worsening heart failure (HF) than placebo, regardless of the presence or absence of diabetes. However, there are no ideas for the cellular mechanisms for the SGLT2 inhibitors (SGLT2i)-induced improvements of HF. Therefore, we investigate whether SGLT2i attenuates the progression of HF in dogs. HF is induced by rapid ventricular pacing for 6 weeks. We administered SGLT2i orally for 14 days from 4 weeks after the start of rapid ventricular pacing, with rapid pacing was continued throughout treatment. In other dogs, we administer SGLT2i orally for 6 weeks immediately after the start of rapid ventricular pacing. SGLT2i treatment improved the pathophysiology of HF. SGLT2i treatment was shown to reduce myocardial apoptosis along with increased AMP-activated protein kinase phosphorylation and decreased Bax/Bcl-2 ratio. SGLT2i could be a novel candidate to prevent the onset and progression of HF.

Academic Significance and Societal Importance of the Research Achievements

糖尿病の有無とは関係なく、SGLT2阻害薬ダパグリフロジンが左室駆出率の低下した慢性心不全患者の心不全入院イベントを抑制することが報告され(DAPA-HF試験)、現在、ダパグリフロジンは、慢性心不全の標準的な治療を受けているにもかかわらず症候性で、かつ左室収縮性の低下した患者に対する処方が推奨されているが、本研究成果より、心不全症状が出現する以前のリスクステージである心不全ステージAやステージBの段階で処方されることで、心不全の発症が抑制されることが示唆された。

Report

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

    (8 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Difference in the prevalence of subclinical left ventricular impairment among left ventricular geometric pattern in a community-based population2020

    • Author(s)
      Hasegawa T, Asakura M, Asanuma H, Amaki M, Takahama H, Sugano Y, Kanzaki H, Yasuda S, Anzai T, Izumi C, Kitakaze M.
    • Journal Title

      J Cardiol.

      Volume: 75 Issue: 4 Pages: 439-446

    • DOI

      10.1016/j.jjcc.2019.09.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arterial stiffening is a crucial factor for left ventricular diastolic dysfunction in a community-based normotensive population2020

    • Author(s)
      Mika M, Kanzaki H, Hasegawa T, Fukuda H, Amaki M, Kim J, Asakura M, Asanuma H, Nishimura M, Kitakaze M.
    • Journal Title

      Int J Cardiol Hypertens.

      Volume: 6 Pages: 100038-100038

    • DOI

      10.1016/j.ijchy.2020.100038

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AST-120, an Adsorbent of Uremic Toxins, Improves the Pathophysiology of Heart Failure in Conscious Dogs.2019

    • Author(s)
      Asanuma H, Chung H, Ito S, Min KD, Ihara M, Takahama H, Funayama M, Imazu M, Fukuda H, Ogai A, Asano Y, Minamino T, Takashima S, Morita T, Sugimachi M, Asakura M, Kitakaze M.
    • Journal Title

      Cardiovasc Drugs Ther.

      Volume: 33 Issue: 3 Pages: 277-286

    • DOI

      10.1007/s10557-019-06875-z

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endogenously released adenosine causes pulmonary vasodilation during the acute phase of pulmonary embolization in dogs.2019

    • Author(s)
      Takahama H, Asanuma H, Tsukamoto O, Ito S, Kitakaze M.
    • Journal Title

      Int J Cardiol Heart Vasc.

      Volume: 24 Pages: 100396-100396

    • DOI

      10.1016/j.ijcha.2019.100396

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cutting Edge Science and Medicine of Adenosine in Patients With Heart Failure2018

    • Author(s)
      Asanuma H, Kitakaze M.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 5 Pages: 1247-1248

    • DOI

      10.1253/circj.CJ-18-0327

    • NAID

      130006726017

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Management of serum phosphate level is an important novel therapeutic target in chronic heart failure.2019

    • Author(s)
      Asanuma H, Fukuda H, Takahama H, Hitsumoto T, Imazu M, Nakajima Y, Ito S, Kitakaze M.
    • Organizer
      第36回 国際心臓研究学会日本部会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of endogenous adenosine on hemodynamics in experimental acute pulmonary embolization.2019

    • Author(s)
      Takahama H, Asanuma H, Ito S, Kitakaze M.
    • Organizer
      第36回 国際心臓研究学会日本部会
    • Related Report
      2019 Research-status Report
  • [Book] 虚血性心疾患 識る・診る・治す・防ぐ2018

    • Author(s)
      小室一成、中村正人
    • Total Pages
      400
    • Publisher
      中山書店
    • ISBN
      9784521745848
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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