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Translational research using molecular form of B-type natriuretic peptide

Research Project

Project/Area Number 21K08126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKyoto University

Principal Investigator

Nishikimi Toshio  京都大学, 医学研究科, 非常勤講師 (80291946)

Co-Investigator(Kenkyū-buntansha) 高濱 博幸  東北大学, 大学病院, 講師 (10570301)
南野 直人  (財)蛋白質研究奨励会, その他部局等, 研究員(移行) (50124839)
中川 靖章  京都大学, 医学研究科, 助教 (70452357)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsBNP / 心不全 / mature BNP / proBNP / total BNP / ANP / N-terminal proBNP / 心臓リモデリング / N-terminal BNP / ARNI / 分子型
Outline of Research at the Start

本申請研究では、慢性心不全で 活性型BNP、ANPを増やすアンギオテンシン受容体/ネプリライシン阻害薬(ARNI)投与前後に mature BNP/total BNP比を測定し、左室リバースリモデリ ングを予知可能か否か、ARNIのresponderか否か、を検討 する。また急性心不全後にmature BNP/total BNP比が左室 リバースリモデリングの予知指標となるのかを検討する。 基礎研究では糖転移酵素によるプロセシングの調節機序の 解明を目指す。

Outline of Final Research Achievements

We have pointed out that the current immunoassay for BNP, a biomarker of heart failure, cross-reacts precursor proBNP and that immunoreactive BNP means proBNP+mature BNP (=total BNP). We have developed a new measurement system for proBNP, mature BNP, and total BNP. We found that patients with acute heart failure and higher mature BNP/total BNP ratio at admission had better improvement in subsequent left ventricular ejection fraction. We also examined changes in natriuretic peptide-related molecules during ARNI treatment. We found that mature BNP, proBNP, total BNP, NT-proBNP, ANP, and BNP were significantly lower in the responder group than in the nonresponder group from 2 to 12 weeks.

Academic Significance and Societal Importance of the Research Achievements

急性心不全が改善した後に左室駆出率が回復する群では入院時のmature BNP/total BNP比率が高いことを見出した。このことは急性心不全に罹患した患者の予後の予測や薬物治療を強化する群の予測に役立つ可能性がある。ARNI治療でナトリウム利尿ペプチド分子種の変化を見ることで、この薬剤のresponder群を2週、4週の早期に検出できる可能性を見出した。このことは、心不全患者の予後予測に役立つだけでなく、nonresponder群に対して早期の新しい介入が可能となり、心不全患者の予後の改善に役立つ可能性がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (23 results)

All 2024 2023 2022 2021 Other

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] Effect of comorbid heart failure assessed by plasma B-type natriuretic peptide level on the activities of daily living in patients with hospitalization-associated disability after aspiration pneumonia.2024

    • Author(s)
      Tamamura Y, Matsuura M, Shiba S, Nishikimi T.
    • Journal Title

      Eur Geriatr Med

      Volume: 15 Issue: 1 Pages: 67-72

    • DOI

      10.1007/s41999-023-00907-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] B-Type Natriuretic Peptide (BNP) Revisited - Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?2022

    • Author(s)
      Nishikimi T, Nakagawa Y.
    • Journal Title

      Bilology (Basel)

      Volume: 11 Issue: 7 Pages: 1034-1034

    • DOI

      10.3390/biology11071034

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CNP, the Third Natriuretic Peptide: Its Biology and Significance to the cardiovascular System2022

    • Author(s)
      Nakagawa Y, Nishikimi T
    • Journal Title

      Bilology (Basel)

      Volume: 11 Pages: 986-986

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cardiac Peptides-Current Physiology, Pathophysiology, Biochemistry, Molecular Biology, and Clinical Application2022

    • Author(s)
      Nishikimi T, Kato J
    • Journal Title

      Biology

      Volume: 11 Issue: 2 Pages: 330-330

    • DOI

      10.3390/biology11020330

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NRSF- GNAO1 Pathway Contributes to the Regulation of Cardiac Ca 2+ Homeostasis2022

    • Author(s)
      Inazumi Hideaki、Kuwahara Koichiro、Nakagawa Yasuaki、et al.
    • Journal Title

      Circulation Research

      Volume: 130 Issue: 2 Pages: 234-248

    • DOI

      10.1161/circresaha.121.318898

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential pitfalls when interpreting plasma BNP levels in heart failure practice.2021

    • Author(s)
      Nishikimi T, Nakagawa Y
    • Journal Title

      Journal of Cardiology

      Volume: 74 Issue: 4 Pages: 269-274

    • DOI

      10.1016/j.jjcc.2021.05.003

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery2021

    • Author(s)
      Kimura A, Takahama H, Nishikimi T, Takashio S, Hayashi T, Nagai-Okatani C, Nakagawa Y, Yasuda S, Anzai T, Minamino N, Izumi C.
    • Journal Title

      ESC Heart Fail.

      Volume: 8 Issue: 6 Pages: 5617-5621

    • DOI

      10.1002/ehf2.13684

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of heart failure and malnutrition, alone and in combination, on rehabilitation effectiveness in patients with hip fracture.2021

    • Author(s)
      Tamamura Y, Matsuura M, Shiba S, Nishikimi T.
    • Journal Title

      Clin Nutr ESPEN.

      Volume: 44 Pages: 356-366

    • DOI

      10.1016/j.clnesp.2021.05.014

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] アンシジオテンシン受容体, ネプリライシン阻害薬(ARNI)と BNP,NT-proBNP の関係とは?2021

    • Author(s)
      錦 見 俊 雄.
    • Journal Title

      循環器内科

      Volume: 89 Pages: 1-6

    • Related Report
      2021 Research-status Report
  • [Presentation] 回復期病棟における潜在性心不全の意義ーARNI使用時のBNPの解釈を含めてー2024

    • Author(s)
      錦見俊雄
    • Organizer
      第89回日本循環器学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 心不全におけるBNP分子型の変化と病態生理学的意義2023

    • Author(s)
      錦見俊雄、中川靖章、木下秀之、稲住英明、柳澤洋、金森敬彦、森内健史、高濱博幸、南野直人
    • Organizer
      第27回日本心不全学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ヒト脳性(もしくはB型)ナトリウム利尿ペプチド(BNP)の生体内挙動と臨床的意義に関する最近の話題2023

    • Author(s)
      錦見俊雄
    • Organizer
      2023年度(第59回)日臨技首都圏支部・関甲信支部 医学検査学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 新しい心不全診療におけるBNP検査の意義についての最新の話題ー来るべき心不全パンデミックに備えてー2023

    • Author(s)
      錦見俊雄
    • Organizer
      第87回日本循環器学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 心血管病におけるナトリウム利尿ペプチドの病態生理学的意義2022

    • Author(s)
      中川靖章、錦見俊雄、桑原宏一郎、柳澤洋、木下秀之、森内健史、金森敬彦、植田洋平、八十田明宏、高濱博幸、南野直人、中尾一和
    • Organizer
      第26回日本心不全学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 転写調節因子NRSFを介した心不全進展の分子メカニズム2022

    • Author(s)
      稲住英明、桑原宏一郎、中川靖章、大矢未来、木下秀之、森内健司、柳澤洋、金森敬彦、錦見俊雄、中尾一和
    • Organizer
      第26回日本心血管内分泌代謝学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肺高血圧症の新規治療ターゲットとしてのTRPC3/C6 ( Classic transient receptor potential channels 3 and 6 (TRPC3/C6) are novel therapeutic target of PAH.)2022

    • Author(s)
      森内健史、中川靖章、木下秀之、西田基宏、森泰生、永田龍、中村一文、錦見俊雄、稲住英明、柳澤洋、金森 敬彦 、大矢未来、中尾一和、桑原宏一郎、木村剛
    • Organizer
      第26回日本心不全学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Genetic and pharmacological inhibition of TRPC3/6 ameliorates pulmonary arterial hypertension in rodent models.2022

    • Author(s)
      森内健史、中川靖章、木下秀之、西田基宏、森泰生、永田龍、中村一文、錦見俊雄、稲住英明、柳澤洋、金森 敬彦 、大矢未来、中尾一和、桑原宏一郎、木村剛
    • Organizer
      第39回国際心臓研究学会 日本部会
    • Related Report
      2022 Research-status Report
  • [Presentation] ENDOTHELIAL CNP-GC-B SYSTEM PLAYS A PROTECTIVE ROLE IN THE DEVELOPMENT OF PULMONARY HYPERTENSION2022

    • Author(s)
      Yanagisawa H, Nakagawa Y, Nishikimi T, Kuwahara K.
    • Organizer
      the 29th Scientific Meeting of the International Society of Hypertension
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] BNP分子型の新しい病態生理学的意義2021

    • Author(s)
      錦見俊雄、中川靖章、 高濱博幸、南野直人
    • Organizer
      第20回日本心血管内分泌代謝学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 心血管病におけるナトリウム利尿ペプチドの病態生理学的意義2021

    • Author(s)
      中川靖章、柳澤洋、錦見俊雄、桑原宏一郎、八十田明宏、中尾一和、木村剛
    • Organizer
      第31回日本循環薬理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] BNP and CNP: new cardiovascular roles and potential as a therapeutic target2021

    • Author(s)
      Yasuaki Nakagawa, Toshio Nishikimi, Koichiro Kuwahara, Hiromu Yanagisawa, Kenji Moriuchi, Hideaki Inazumi, Naoto Minamino, Kazuwa Nakao, Takeshi Kimura
    • Organizer
      The 85th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY
    • Related Report
      2021 Research-status Report
  • [Remarks] 京都大学医学部附属病院循環器内科 心血管内分泌代謝グループ

    • URL

      http://kyoto-u-cardio.jp/kisokenkyu/endocrine/

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Remarks] 京大病院 循環器内科 心血管内分泌代謝グループ

    • URL

      http://kyoto-u-cardio.jp/kisokenkyu/endocrine/

    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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