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2013 Fiscal Year Final Research Report

Translational research of circulation-regulated peptide using B-type natriuretic peptide and adrenomedullin

Research Project

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Project/Area Number 23591041
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKyoto University

Principal Investigator

NISHIKIMI Toshio  京都大学, 医学(系)研究科(研究院), その他 (80291946)

Co-Investigator(Kenkyū-buntansha) KUWAHARA Koichiro  京都大学, 医学部付属病院医学部付属病院内分泌代謝内科, 講師 (30402887)
NAKAGAWA Yasuaki  京都大学, 内分泌代謝内科, 助教 (70452357)
Co-Investigator(Renkei-kenkyūsha) MINAMINO Naoto  国立循環器病研究センター研究所, 薬理部, 部長 (50124839)
Project Period (FY) 2011 – 2013
KeywordsB 型ナトリウム利尿ペプチド / アドレノメデュリン / 循環ペプチド / 心不全 / ノックアウトマウス / proBNP / 脂肪組織
Research Abstract

We investigated the translational research of circulation-regulated peptide using B-type natriuretic peptide and adrenomedullin. We newly developed the immunofluorescent assay for proBNP and total BNP(= BNP32 + proBNP). Using this immunofluorescent assay system we found that proBNP is about 70% of total BNP immunoreactivity. ProBNP level increases with age. ProBNP level is increased in heart failure in proportion to its severity. ProBNP/total BNP ratios are greater in chronic renal failure patients than in normal subjects. We successfully produced fat tissue specific deficient AM knockout mouse. The phenotype under normal diet reveals no differences compared with wild type mouse such as body weight, body height, and fat tissue amount.

  • Research Products

    (31 results)

All 2014 2013 2012 2011

All Journal Article (18 results) (of which Peer Reviewed: 14 results) Presentation (12 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Epicardial-derived adrenomedullin drives cardiac hyperplasia during embryogenesis2014

    • Author(s)
      Wetzel-Strong SE, Nishikimi T, 他3名
    • Journal Title

      Dev Dyn

      Volume: 243 Pages: 243-56

    • Peer Reviewed
  • [Journal Article] Complexity of molecular forms of B-type natriuretic peptide in heart failure2013

    • Author(s)
      Nishikimi T, Kuwahara K, Nakagawa Y, Minamino N, 他2名
    • Journal Title

      Heart

      Volume: 99 Pages: 677-9

    • Peer Reviewed
  • [Journal Article] Direct immunochemiluminescent assay for proBNP and total BNP in human plasma proBNP and total BNP levels in normal and heart failure2013

    • Author(s)
      Nishikimi T, Kuwahara K, Nakagawa Y, Minamino N, 他13名
    • Journal Title

      PLoS One

      Volume: 8 Pages: e53233

    • Peer Reviewed
  • [Journal Article] Increased expression of HCN channels in the ventricular myocardium contributes to enhanced arrhythmicity in mouse failing hearts2013

    • Author(s)
      Kuwabara Y, Kuwahara K, Nakagawa Y, Nishikimi T, 他13名
    • Journal Title

      J Am Heart Assoc

      Volume: 2 Pages: e000150

    • Peer Reviewed
  • [Journal Article] Adrenomedullin in cardiovascular disease : a useful biomarker, its pathological roles and therapeutic application2013

    • Author(s)
      Nishikimi T, Kuwahara K, Nakagawa Y, 他2名
    • Journal Title

      Curr Protein Pept Sci

      Volume: 14 Pages: 256-67

    • Peer Reviewed
  • [Journal Article] Angiotensin II type 1a receptor signalling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy2013

    • Author(s)
      Yasuno S, Kuwahara K, Nakagawa Y, Nishikimi T, 他7名
    • Journal Title

      Br J Pharmacol

      Volume: 170 Pages: 1384-95

    • Peer Reviewed
  • [Journal Article] ストローマとナトリウム利尿ペプチド-急性心筋梗塞の病態生理的意義と臨床応用-2013

    • Author(s)
      錦見俊雄
    • Journal Title

      循環器内科

      Volume: 74 Pages: 174-180

  • [Journal Article] The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure2012

    • Author(s)
      Nishikimi T, Kuwahara K, Nakagawa Y, 他7名
    • Journal Title

      Heart

      Volume: 98 Pages: 152-61

    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of the fetal cardiac gene program2012

    • Author(s)
      Kuwahara K, Nishikimi T, Nakao K
    • Journal Title

      J Pharmacol Sci

      Volume: 119 Pages: 198-203

    • Peer Reviewed
  • [Journal Article] Do plasma levels of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) increase in diastolic dysfunction as well as in systolic dysfunction?2012

    • Author(s)
      Nishikimi T
    • Journal Title

      Circ J

      Volume: 76 Pages: 2540-1

    • Peer Reviewed
  • [Journal Article] Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice2012

    • Author(s)
      Minami T, Kuwahara K, Nakagawa Y, Nishikimi T, 他18名
    • Journal Title

      EMBO J

      Volume: 31 Pages: 4428-40

    • Peer Reviewed
  • [Journal Article] 心疾患のバイオマーカーとしてのBNPの意義ー基礎的・臨床的観点からー2012

    • Author(s)
      錦見俊雄
    • Journal Title

      日本臨床

      Volume: 70 Pages: 774-784

  • [Journal Article] BNP、ANPと高血圧2012

    • Author(s)
      錦見俊雄
    • Journal Title

      血圧

      Volume: 19 Pages: 884-889

  • [Journal Article] 降圧薬としてのエンドセリン拮抗薬、PDE5阻害薬—治療抵抗性高血圧におけるエンドセリン拮抗薬、PDE5阻害薬の可能性—2012

    • Author(s)
      錦見俊雄
    • Journal Title

      循環器内科

      Volume: 72 Pages: 515-520

  • [Journal Article] Diverse molecular forms of plasma B-type natriuretic peptide in heart failure2011

    • Author(s)
      Nishikimi T, Minamino N, Nakao K
    • Journal Title

      Curr Heart Fail Rep

      Volume: 8 Pages: 140-6

    • Peer Reviewed
  • [Journal Article] Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides2011

    • Author(s)
      Nishikimi T, Kuwahara K, Nakao K
    • Journal Title

      J Cardiol

      Volume: 57 Pages: 131-40

    • Peer Reviewed
  • [Journal Article] Zinc-finger protein 90 negatively regulates neuron- restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes2011

    • Author(s)
      Hata L, Kuwahara K, Nakagawa Y, Nishikimi T, 他12名
    • Journal Title

      J Mol Cell Cardiol

      Volume: 50 Pages: 972-81

    • Peer Reviewed
  • [Journal Article] Japanese-Western consensus meeting on biomarkers2011

    • Author(s)
      Maisel AS, Minamino N, Nishikimi T, 他12名
    • Journal Title

      Int Heart J

      Volume: 52 Pages: 253-65

    • Peer Reviewed
  • [Presentation] Molecular mechanism of lower processing rate in human proBNP : importance of the distance between the O-glycosylation and cleavage sites2014

    • Author(s)
      Toshio Nishikimi, Yasuaki Nakagawa, Naoto Minamino, Koichiro Kuwahara, 他9名
    • Organizer
      日本循環器学会総会
    • Place of Presentation
      東京
    • Year and Date
      20140321-23
  • [Presentation] 心不全におけるBNP前駆体proBNPの病態生理的意義2013

    • Author(s)
      錦見俊雄
    • Organizer
      日本心血管内分泌代謝学会
    • Place of Presentation
      大阪(イブニングセミナー)
    • Year and Date
      20131122-23
  • [Presentation] O-glycosylated Pro B-type Natriuretic Peptide is Cleaved intracellularly By Furin in Ventricular Myocytes and Atrial Myocytes : Importance of the Distance Between the O-glycosylation Sites and Cleaved Sites2013

    • Author(s)
      Toshio Nishikimi, Yasuaki Nakagawa, Naoto Minamino, Koichiro Kuwahara, 他9名
    • Organizer
      American Heart Association Annual Meeting
    • Place of Presentation
      Dallas, USA
    • Year and Date
      20131115-18
  • [Presentation] B型ナトリウム利尿ペプチド研究の最前線2013

    • Author(s)
      錦見俊雄
    • Organizer
      日本高血圧学会総会
    • Place of Presentation
      大阪(シンポジウム)
    • Year and Date
      20131023-25
  • [Presentation] ナトリウム利尿ペプチドBNP、ANPの最新知見とその臨床応用2013

    • Author(s)
      錦見俊雄
    • Organizer
      日本自動分析学会
    • Place of Presentation
      横浜(ランチョンセミナー)
    • Year and Date
      2013-10-12
  • [Presentation] BNP revisited2012

    • Author(s)
      錦見俊雄
    • Organizer
      第16回日本心血管内分泌学会
    • Place of Presentation
      東京(ワークショップ)
    • Year and Date
      20121123-24
  • [Presentation] Direct immunoassay for proBNP and total BNP in human plasma–proBNP and total BNP levels in healthy and heart failure patients2012

    • Author(s)
      Nishikimi T, Nakagawa1 Y, Kuwahara K, Minamino N, 他8名
    • Organizer
      24th International Society of Hypertension
    • Place of Presentation
      Sidney, Australia
    • Year and Date
      20120930-1004
  • [Presentation] ヒト血漿におけるproBNP、total BNP直接測定法の確立ー健常者、心不全患者での検討ー2012

    • Author(s)
      錦見俊雄、中川靖章、桑原宏一郎、南野直人, 他11名
    • Organizer
      第35回日本高血圧学会
    • Place of Presentation
      名古屋
    • Year and Date
      20120922-24
  • [Presentation] proBNP、total BNP直接化学発光測定法の確立ー心不全患者における検討ー2012

    • Author(s)
      錦見俊雄、中川靖章、桑原宏一郎、南野直人, 他12名
    • Organizer
      第60回日本心臓病学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      20120914-16
  • [Presentation] BNP関連ペプチドの最新知見2012

    • Author(s)
      錦見俊雄
    • Organizer
      The76th Annual Scientific Meeting of The Japanese Circulation
    • Place of Presentation
      Fukuoka, Japan(ランチョンセミナー)
    • Year and Date
      20120316-18
  • [Presentation] 高血圧性左室肥大・潜在性心機能低下のサロゲートマーカーとしての血漿BNP測定の意義と問題点2011

    • Author(s)
      錦見俊雄
    • Organizer
      第34回日本日本高血圧学会総会
    • Place of Presentation
      宇都宮市(Up to Date)
    • Year and Date
      20111020-22
  • [Presentation] Analysis of circulating glycosylated N-terminal proBNP and nonglycosylated N-terminal proBNP in patients with heart failure (HF) and chronic renal failure (CRF) on hemodialysis2011

    • Author(s)
      Nishikimi T, Minamino N, Kuwahara1 K, Nakagawa Y, 他5名
    • Organizer
      European Society of Cardiology 33rd Annual Congress
    • Place of Presentation
      Paris, France
    • Year and Date
      20110827-31
  • [Patent(Industrial Property Rights)] proBNP-108の新規用途2013

    • Inventor(s)
      錦見俊雄、他1名
    • Industrial Property Rights Holder
      錦見俊雄、他2名
    • Industrial Property Number
      特許5362487
    • Acquisition Date
      2013-09-13
    • Overseas

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Published: 2015-07-16  

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