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Study of sugar chains binding to BNP precursors; 1. Structure analysis, 2. Molecular mechanism, 3. relationship with heart failure condition

Research Project

Project/Area Number 18K08103
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) 中川 靖章  京都大学, 医学研究科, 助教 (70452357)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心不全 / BNP / proBNP / 糖鎖修飾 / 分子型 / 精製 / ゲル濾過 / 質量分析装置 / 糖鎖構造 / 糖鎖 / プロセシング
Outline of Final Research Achievements

The current assay for BNP system cross-reacts precursor proBNP, indicating that BNP means proBNP + BNP (= total BNP). The applicant created a new assay system for the proBNP and total BNP, which enabled the measurement of the proBNP / total BNP ratio and showed that this ratio was higher in severe chronic heart failure patients. When we examined the proBNP / total BNP ratio in acute heart failure, we found the proBNP / total BNP ratio was lower in mild heart failure, which make cGMP / BNP ratio increasing to compensate for heart failure. Deteriorating renal function during treatment for acute heart failure is well known sign for poor prognosis. Therefore, early detection is important. In this study, we found that the NT-proBNP / mature BNP ratio increased preceding to the deterioration of renal function in acute heart failure patients.

Academic Significance and Societal Importance of the Research Achievements

急性心不全の代償機構としてproBNP/total BNP比率を下げて代償することは新規の機序であり、今後の心不全の治療や診断に応用ができる可能性がある。proBNP/total BNP比率を決めているのはproBNPへの糖鎖修飾であり、糖鎖修飾の機序を解明することで心不全の患者の予後改善に結びつく可能性がある。急性心不全の治療中の腎機能悪化の早期発見の指標は、これまでたくさんの研究がなされてきたが、決定的なものはなかった。腎機能悪化を早期に予知するほど予防、治療のための介入も早くなり、心不全患者の予後の改善に結びつく可能性が高い。今回の研究で入院3日目に有意な変化が見出され期待できる。

Report

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

    (27 results)

All 2020 2019 2018 2017 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (13 results) (of which Int'l Joint Research: 5 results) Remarks (3 results)

  • [Journal Article] Heart failure assessed based on plasma B-type natriuretic peptide (BNP) levels negatively impacts activity of daily living in patients with hip fracture.2020

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

      PLoS One

      Volume: 15 Issue: 8 Pages: e0237387-e0237387

    • DOI

      10.1371/journal.pone.0237387

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Change in the NT‐proBNP/Mature BNP Molar Ratio Precedes Worsening Renal Function in Patients With Acute Heart Failure: A Novel Predictor Candidate for Cardiorenal Syndrome2019

    • Author(s)
      Takahama Hiroyuki、Nishikimi Toshio、et al
    • Journal Title

      Journal of the American Heart Association

      Volume: 8 Issue: 17

    • DOI

      10.1161/jaha.118.011468

    • NAID

      120006878493

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Mixture of Glycosylated proBNP and BNP-32 Is a Suitable Calibrator for BNP Immunoassays2019

    • Author(s)
      Masuta K, Funatsuki K, Inoue Y, Masud I, Nishikimi T, Nakagawa Y, Horii K, Nishi H. Irgarashi M, Ota N
    • Journal Title

      Open Journal of Clinical Diagnostics

      Volume: 9 Issue: 02 Pages: 51-63

    • DOI

      10.4236/ojcd.2019.92004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dose impaired processing of pro-B-type (or brain) natriuretic peptide cause decreased plasma BNP levels in obese heart failure patients?2019

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

      Ann Transl Med

      Volume: 7 Issue: S6 Pages: S221-S221

    • DOI

      10.21037/atm.2019.08.56

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Superiority of proatrial natriuretic peptide in the prognostic power in patients with acute decompensated heart failure on hospital admission: comparison with B-type natriuretic peptide and other natriuretic peptide forms2019

    • Author(s)
      Takashio Seiji、Takahama Hiroyuki、et al.
    • Journal Title

      Open Heart

      Volume: 6 Issue: 2 Pages: e001072-e001072

    • DOI

      10.1136/openhrt-2019-001072

    • NAID

      120006878492

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 心不全診療におけるBNP解釈のピットフォール -BNPを課題浄化もしくは過小評価する病態-2019

    • Author(s)
      錦見俊雄、中川靖章
    • Journal Title

      Heart view

      Volume: 8 Pages: 28-36

    • Related Report
      2019 Research-status Report
  • [Journal Article] Atrial and brain natriuretic peptides: Hormones secreted from the heart2019

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

      Peptides

      Volume: 111 Pages: 18-25

    • DOI

      10.1016/j.peptides.2018.05.012

    • NAID

      120006817603

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cutting Edge of Brain Natriuretic Peptide (BNP) Research ― The Diversity of BNP Immunoreactivity and Its Clinical Relevance ―2018

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

      Circulation Journal

      Volume: 82 Issue: 10 Pages: 2455-2461

    • DOI

      10.1253/circj.CJ-18-0824

    • NAID

      130007489414

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2018-09-25
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adrenomedullin as a Biomarker2018

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

      Heart Fail Clin

      Volume: 14 Issue: 1 Pages: 49-55

    • DOI

      10.1016/j.hfc.2017.08.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ratio of pro-B-type natriuretic peptide (BNP) to total BNP is decreased in mild, but not severe, acute decompensated heart failure patients: A novel compensatory mechanism for acute heart failure2018

    • Author(s)
      Takahama Hiroyuki、Takashio Seiji、Nishikimi Toshio、Hayashi Tomohiro、Nagai-Okatani Chiaki、Nakagawa Yasuaki、Amaki Makoto、Ohara Takahiro、Hasegawa Takuya、Sugano Yasuo、Kanzaki Hideaki、Yasuda Satoshi、Kangawa Kenji、Minamino Naoto、Anzai Toshihisa
    • Journal Title

      International Journal of Cardiology

      Volume: 258 Pages: 165-171

    • DOI

      10.1016/j.ijcard.2017.12.047

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP:Case report.2017

    • Author(s)
      Nakagawa Y, Nishikimi T, Sakai H, Ohno S, Kinoshita H, Inazumi H, Moriuchi K, Kuwahara K, Horie M, Kimura T.
    • Journal Title

      Clinical Biochemistry

      Volume: 52 Pages: 148-152

    • DOI

      10.1016/j.clinbiochem.2017.10.019

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] How do you interpret the value of BNP or NT-proBNP after ARNI therapy in heart failure patients ? Lessons from PARADIGM-HF study2020

    • Author(s)
      錦見俊雄
    • Organizer
      第 84回 日本循環器学会学術集会総会 TOPICS
    • Related Report
      2020 Annual Research Report
  • [Presentation] 心不全におけるアドレノメデュリンとST2-病態生理学的役割とバイオマーカーとしての意義-2020

    • Author(s)
      錦見俊雄
    • Organizer
      第24回日本心不全学会学術集会 シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] BNP分子型の病態生理的意義2020

    • Author(s)
      錦見俊雄
    • Organizer
      第24回日本心血管内分泌代謝学会 シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] NRSF-GNAO1-CaMK2 axis exacerbates cardiac remodeling and progresses heart failure by impairing Ca2+homeostasis2020

    • Author(s)
      Inazumi H, Kuwahara K, Kuwabara Y, Nakagawa Y, Kinoshita H, Moriuchi K, Yanagisawa H, Nishikimi T, Oya M, Yarnada M, Kashihara T, Kurebayashi N, Sugihara M, Nakao K, Kimura T.
    • Organizer
      ESC Congress 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increased Gαo expression plays a pivotal role in the progression of heart failure by impairing Ca2+ handling2019

    • Author(s)
      Hideaki Inazumi, Koichiro Kuwahara, Yoshihiro Kuwabara, Yasuaki Nakagawa, Hideyuki Kinoshita、Kenji Moriuchi, Hiromu Yanagisawa, Toshio Nishikimi,Kazuwa Nakao, Takeshi Kimura
    • Organizer
      BCVS2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased Gao expression underlies cardiac dysfunction and lethal arrhythmias accompanied with abnormal Ca2+ handling2019

    • Author(s)
      Inazumi H, Kuwahara K, Kuwabara Y, Nakagawa Y, Kinoshita H, Moriuchi K, Yanagisawa H, Nishikimi T, Oya M, Yamada M, Kashihara T, Kurebayashi N, Sugihara M, Nakao K, Kimura T.
    • Organizer
      European Society of Cardiology2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抑制性G蛋白サブユニットGαoの発現亢進はCa2+ handlingの異常を介して心不全進展にかかわる2019

    • Author(s)
      稲住英明 桑原宏一郎 桒原佳宏 中川靖章 木下秀之 森内健史 柳澤洋 錦見俊雄 大矢未来 山田充彦 柏原俊英 呉林なごみ 中尾一和 木村剛
    • Organizer
      第56回日本臨床分子医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] TRPC3/TRPC6チャネルを標的とした新規肺高血圧症治療の検討2019

    • Author(s)
      森内健史 木下秀之 中川靖章 西田基宏 森泰生 中村一文 錦見俊雄 稲住英明 柳澤洋 大矢未来 中尾一和 桑原宏一郎 木村剛
    • Organizer
      第4回J-ISCP年次学術集会 国際心血管薬物療法学会日本部会(J-ISCP)
    • Related Report
      2019 Research-status Report
  • [Presentation] Increased expression of Gαo plays a pivotal role in the progression of heart failure by impairing Ca2+ homeostasis2019

    • Author(s)
      H Inazumi, K Kuwahara, Y Kuwabara, Y Nakagawa, H Kinoshita, K Moriuchi, H Yanagisawa , T Nishikimi , M Oya, M Yamada, T Kashihara, N Kurebayashi, M Sugihara, K Nakao, T Kimura
    • Organizer
      第36回国際心臓研究学会日本部会
    • Related Report
      2019 Research-status Report
  • [Presentation] PRO-B-TYPE NATRIURETIC PEPTIDE (BNP) TO TOTAL BNP RATIO IS INVOLVED IN THE PATHOPHYSIOLOGY OF ACUTE AND CHRONIC HEART FAILURE: ELUCIDATION OF MOLECULAR MECHANISM2018

    • Author(s)
      Nishikimi T, Nakagawa Y,他9名
    • Organizer
      27th Scientific Meeting of the International-Society-of-Hypertension
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] G蛋白サブユニットGαoのCa2+ handling恒常性および心収縮能維持における意義の解明2018

    • Author(s)
      稲住英明、桑原宏一郎、桒原佳宏、中川靖章、木下秀之、錦見俊雄、呉林なごみ、山田充彦、柏原俊英、中尾一和、木村剛
    • Organizer
      第55回日本臨床分子医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 心不全モデルマウスにおけるG蛋白サブユニットGαoの発現亢進はCa2+ handlingの異常をきたし心収縮能低下に関与する2018

    • Author(s)
      稲住英明、桑原宏一郎、桒原佳宏、中川靖章、木下秀之、錦見俊雄、呉林なごみ、山田充彦、中尾一和、木村剛
    • Organizer
      第91回日本内分泌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Impact of the superior predicting ability of pro-atrial natriuretic peptide level on admission for future clinical adverse events in patients with acute heart failure: Comparison with B-type natriuretic peptide level measured using conventional assay2018

    • Author(s)
      Hiroyuki Takahama,Seiji Takashio, Toshio Nishikimi, 他他14名
    • Organizer
      American Heart Association's annual Scientific Sessions meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 京都大学医学部付属病院循環器内科 心血管内分泌代謝グループ

    • URL

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

    • Related Report
      2020 Annual Research Report
  • [Remarks] 京都大学医学部付属病院循環器内科 心血管内分泌代謝グループ

    • URL

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

    • Related Report
      2019 Research-status Report
  • [Remarks] 京都大学医学部付属病院循環器内科 心血管内分泌代謝グループ

    • URL

      http://kyoto-u-cardio.jp/kisokenkyu/cat236/

    • Related Report
      2018 Research-status Report

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

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