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Mechanisms of reduced lifespan of erythrocytes in chronic heart failure

Research Project

Project/Area Number 18K08055
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionHyogo Medical University (2022)
Hyogo University of Health Sciences (2018-2021)

Principal Investigator

Tsujino Takeshi  兵庫医科大学, 薬学部, 教授 (90283887)

Co-Investigator(Kenkyū-buntansha) 内藤 由朗  兵庫医科大学, 医学部, 講師 (10446049)
増山 理  兵庫医科大学, 医学部, 教授 (70273670)
伊藤 都裕  兵庫医療大学, 薬学部, 助教 (20767363)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords心不全 / 心腎貧血症候群 / ダール食塩感受性ラット / 貧血 / 腎不全 / フマル酸ジメチル / 酸化ストレス / 慢性心不全 / 鉄欠乏
Outline of Final Research Achievements

Anemia in patients with chronic heart failure (CHF) is a sign of poor prognosis. However, mechanisms of anemia in CHF are thought to be multifatorial and not well understood. We examined the mechanisms of anemia in Dahl salt-sensitive (DS) rat, a model of chronic heart failure. We found that reduced lifespan of erythrocytes is the major cause of anemia. Eryptosis is a programmed death of nucleus-free, iron-filled red blood cells. We found that eryptosis induced by oxidative stress was a cause of reduced lifespan of erythrocytes in DS rats. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the cellular defense against toxic and oxidative insults. We found that dimethyl fumarate, an activator of Nrf2, prevented anemia, cardiac and renal fibrosis and inflammation, and prolonged survival in DS rats.

Academic Significance and Societal Importance of the Research Achievements

慢性心不全患者において、慢性腎不全と貧血が合併した病態は心腎貧血症候群として知られ、予後不良の因子であるが、その機序は十分解明されたとはいえず、治療法は確立されていない。我々は慢性心不全の動物モデルであるDahl食塩感受性(DS)ラットに合併する貧血と心臓・腎臓障害にフマル酸ジメチル(DMF)が有効であることを示した。DMFは多発性硬化症の治療薬としてすでに認可されており、drug repositioning により、心腎貧血症候群の治療薬の候補となりうることが示された。確立された治療法のない心腎貧血症候群に対し有効な治療法が見つかれば、その学術的・社会的意義は大きい。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (5 results)

  • [Journal Article] Juzentaihoto improves adenine-induced chronic renal failure in BALB/c mice via suppression of renal fibrosis and inflammation.2022

    • Author(s)
      Ito S, Manabe E, Dai Y, Ishihara M, Tsujino T.
    • Journal Title

      J Pharmacol Sci .

      Volume: 148 Issue: 1 Pages: 172-178

    • DOI

      10.1016/j.jphs.2021.10.009

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 心腎貧血症候群モデルラットにおける貧血の機序2021

    • Author(s)
      辻野 健
    • Journal Title

      BIO Clinica

      Volume: 36 Pages: 237-239

    • Related Report
      2020 Research-status Report
  • [Journal Article] Reduced lifespan of erythrocytes in Dahl/Salt sensitive rats is the cause of the renal proximal tubule damage2020

    • Author(s)
      Manabe E, Ito S, Ohno Y, Tanaka T, Naito Y, Sasaki N, Asakura M, Masuyama T, Ishihara M, Tsujino T.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 22023-22023

    • DOI

      10.1038/s41598-020-79146-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neutrophil/lymphocyte ratio elevation in renal dysfunction is caused by distortion of leukocyte hematopoiesis in bone marrow.2019

    • Author(s)
      Ito S, Ohno Y, Tanaka T, Kobuchi S, Ayajiki K, Manabe E, Masuyama T, Jun-Ichi S, Tsujino T.
    • Journal Title

      Renal Failure

      Volume: 41 Issue: 1 Pages: 284-293

    • DOI

      10.1080/0886022x.2019.1597736

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] フマル酸ジメチルは心臓におけるTGF-β1及びICAM-1発現を抑制 し、Dahl食塩感受性ラットにおける全生存率を改善する2023

    • Author(s)
      山谷 冬華、伊藤 都裕 、新井 優里、辻野 健
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Dahl食塩感受性高血圧ラットに合併する貧血に対するエリスロポエチン製剤と鉄製剤の治療効果2019

    • Author(s)
      小海 龍矢、伊藤 都裕、真鍋 恵理、石原 正治、辻野 健
    • Organizer
      第8回 臨床高血圧フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性腎臓病に対する十全大補湯の効果2019

    • Author(s)
      柳原 俊、伊藤 都裕、戴 毅、辻野 健
    • Organizer
      第8回 臨床高血圧フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] アデニン誘導性腎障害モデルマウスにおけるNLR上昇の機序の検討2019

    • Author(s)
      柳生 未来介、伊藤 都裕、辻野 健
    • Organizer
      第8回 臨床高血圧フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性腎不全における好中球/リンパ球比(N/L比)上昇の機序の検討2018

    • Author(s)
      伊藤都裕、真鍋恵理、増山理、辻野健
    • Organizer
      第7回 臨床高血圧フォーラム
    • Related Report
      2018 Research-status Report

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

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