• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of new heart failure treatment using DPP-4 inhibitors-The role of adenosine

Research Project

Project/Area Number 24390203
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

KITAKAZE Masafumi  独立行政法人国立循環器病研究センター, 研究開発基盤センター, 部長 (20294069)

Co-Investigator(Kenkyū-buntansha) ASANUMA Hiroshi  京都府立医科大学, 医学研究科, 特任准教授 (20416217)
ASAKURA Masanori  国立循環器病研究センター, 研究開発基盤センター, 室長 (80443505)
YAMAZAKI Satoru  国立循環器病研究センター, 研究所, 室長 (70348796)
Research Collaborator NAKANO Astushi  
IHARA Madoka  
MIN Kyung-Duk  
ITO Shin  
SHINDO Kazuhiro  
IMAZU Miki  
TAKAHASHI Ayako  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Keywordsアデノシン / 心不全 / トランスレーショナル研究
Outline of Final Research Achievements

It has been reported that GLP-1 and DPP-4 inhibitors improves the pathophysiology of heart failure (HF). On the other hand, adenosine is a well-established cardioprotective molecule. Interestingly, several reports have indicated that DPP-4 forms a complex with adenosine deaminase (ADA) in immune cells and that ADA regulates DPP-4-mediated intracellular signaling. Because circulating adenosine is eliminated by ADA activity, ADA inhibition by DPP-4 inhibitors may mediated cardioprotection via an adenosine-dependent mechanisms. The present study elucidated the cardioprotective mechanism of DPP-4 inhibitor in various models of HF. The increase in GLP-1 level induce by DPP-4 inhibitor reduces myocardial damage via GLP-1 receptor-mediated activation of the adenosine A1 receptor-PKC α-cAMP response element binding protein (CREB) signaling cascade in ischemia-reperfusion model. These findings support the therapeutic potential of this interaction between GLP-1 and adenosine for HF.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (35 results)

All 2015 2014 2013 2012

All Journal Article (20 results) (of which Peer Reviewed: 16 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (10 results) Book (5 results)

  • [Journal Article] An interaction between GLP-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia/reperfusion injury.2015

    • Author(s)
      Ihara M, Asanuma H, Yamazaki S, Kato H, Asano Y, Shinozaki Y, Mori H, Minamino T, Asakura M, Sugimachi M, Mochizuki N, Kitakaze M.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: in press Issue: 10 Pages: 1287-1297

    • DOI

      10.1152/ajpheart.00835.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase2015

    • Author(s)
      T. Hayashi, Y. Asano, Y. Shintani, H. Aoyama, H. Kioka, O. Tsukamoto, M. Hikita, K. Shinzawa-Itoh, K. Takajuji, S. Higo, H. Kato, S. Yamazaki, K. Matsuoka, A. Nakano, H. Asanuma, M. Asakura, T. Minamino, Y. Goto, T. Ogura, M. Kitakaze, I. Komuro, Y. Sakata, T. Tsukihara, S. Yoshikawa, S. Takashima
    • Journal Title

      Proc. Nat. Acad. Sci. U.S.A.

      Volume: 112 Issue: 5 Pages: 1553-1558

    • DOI

      10.1073/pnas.1419767112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5.2015

    • Author(s)
      Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S.
    • Journal Title

      Nat Commun.

      Volume: 6 Issue: 1 Pages: 6137-6137

    • DOI

      10.1038/ncomms7137

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease.2014

    • Author(s)
      Imazu M, Takahama H, Asanuma H, Funada A, Sugano Y, Ohara T, Hasegawa T, Asakura M, Kanzaki H, Anzai T, Kitakaze M.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 307(10) Issue: 10 Pages: H1504-H1511

    • DOI

      10.1152/ajpheart.00331.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: Role of NO.2014

    • Author(s)
      Asanuma H, Sanada S, Asakura M, Asano Y, Kim J, Shinozaki Y, Mori H, Minamino T, Takashima S,Kitakaze M.
    • Journal Title

      Hypertens Res.

      Volume: 37(8) Issue: 8 Pages: 716-23

    • DOI

      10.1038/hr.2014.70

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart.2014

    • Author(s)
      Matsuoka K, Asano Y, Higo S, Tsukamoto O, Yan Y, Yamazaki S, Matsuzaki T, Kioka H, Kato H, Uno Y, Asakura M, Asanuma H, Minamino T, Aburatani H, Kitakaze M, Komuro I, Takashima S.
    • Journal Title

      FASEB J.

      Volume: 28(4) Issue: 4 Pages: 1870-9

    • DOI

      10.1096/fj.13-245522

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of intra-mitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation2013

    • Author(s)
      Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Tkafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y and Takashima S
    • Journal Title

      PNAS

      Volume: 111 Issue: 1 Pages: 273-278

    • DOI

      10.1073/pnas.1318547111

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dipeptidyl-peptidase IV inhibition improves pathophysiology of heart failure and increases survival rate in pressure-overloaded mice.2013

    • Author(s)
      Takahashi A, Asakura M, Ito S, Min KD, Shindo K, Yan Y, Liao Y, Yamazaki S, Sanada S, Asano Y, Ishibashi-Ueda H, Takashima S, Minamino T, Asanuma H, Mochizuki N, Kitakaze M
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 304(10) Issue: 10 Pages: H1361-H1369

    • DOI

      10.1152/ajpheart.00454.2012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liposomal amiodarone augments anti-arrhythmic effects and reduces hemodynamic adverse effects in an ischemia/reperfusion rat model.2013

    • Author(s)
      Takahama H, Shigematsu H, Asai T, Matsuzaki T, Sanada S, Fu HY, Okuda K, Yamato M, Asanuma H, Asano Y, Asakura M, Oku N, Komuro I, Kitakaze M, Minamino T.
    • Journal Title

      Cardiovasc Drugs Ther.

      Volume: 27 Issue: 2 Pages: 125-132

    • DOI

      10.1007/s10557-012-6437-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Derivation of a mathematical expression for predicting the time to cardiac events in patients with heart failure: a retrospective clinical study.2013

    • Author(s)
      Yoshida A, Asakura M, Asanuma H, Ishii A, Hasegawa T, Minamino T, Takashima S, Kanzaki H, Washio T, Kitakaze M.
    • Journal Title

      Hypertens Res.

      Volume: 36 Issue: 5 Pages: 450-456

    • DOI

      10.1038/hr.2012.200

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] J-WIND試験から学ぶ Evidence & Pitfall2013

    • Author(s)
      北風政史、金智隆、浅沼博司、朝倉正紀
    • Journal Title

      医学のあゆみ

      Volume: 244 Pages: 1311-1316

    • Related Report
      2013 Annual Research Report
  • [Journal Article] カルシウム拮抗薬2013

    • Author(s)
      浅沼博司、北風政史
    • Journal Title

      The Lipid

      Volume: 24 Pages: 43-50

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Direct comparison of the diagnostic capability of cardiovascular magnetic resonance and endomyocardial biopsy in patients with heart failure2013

    • Author(s)
      Yoshida A, I shibashi-Ue da H, Yamada N, Kanzaki H, Hasegawa T, Takahama H, Amaki M, Asakura M, Kitakaze M
    • Journal Title

      European Journal of Heart Failure

      Volume: 15 Issue: 2 Pages: 166-175

    • DOI

      10.1093/eurjhf/hfs206

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs2012

    • Author(s)
      Yoshida A, Asanuma H, Sasaki H, Sanada S, Yamazaki S, Asano Y, Shinozaki Y, Mori H, Shimouchi A, Sano M, Asakura M, Minamino T, Takashima S, Sugimachi M, Mochizuki N, Kitakaze M.
    • Journal Title

      Cardiovasc Drugs Ther.

      Volume: 26 Issue: 3 Pages: 217-226

    • DOI

      10.1007/s10557-012-6381-5

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum blood urea nitrogen and plasma brain natriuretic Peptide and low diastolic blood pressure predict cardiovascular morbidity and mortality following discharge in acute decompensated heart failure patients.2012

    • Author(s)
      Chen CY, Yoshida A, Asakura M, Hasegawa T, Takahama H, Amaki M, Funada A, Asanuma H, Yokoyama H,Kim J, Kanzaki H, Kitakaze M.
    • Journal Title

      Circ J.

      Volume: 76 Pages: 2372-2379

    • NAID

      10030874757

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma adiponectin levels predict cardiovascular events in the observational Arita Cohort Study in Japan: the importance of the plasma adiponectin levels.2012

    • Author(s)
      Chen CY, Asakura M, Asanuma H, Hasegawa T, Tanaka J, Toh N, Min KD, Kanzaki H, Takahama H, Amaki M, Itoh Y, Ichien G, Okumoto Y, Funahashi T, Kim J, Kitakaze M.
    • Journal Title

      Hypertens Res.

      Volume: 35 Issue: 8 Pages: 843-848

    • DOI

      10.1038/hr.2012.42

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CB1 cannabinoid receptor deficiency promotes cardiac remodeling induced by pressure overload in mice.2012

    • Author(s)
      Liao Y, Bin J, Luo T, Zhao H, Ledent C, Asakura M, Xu D, Ta kashima S, Kitakaze M
    • Journal Title

      Int J Cardiol

      Volume: (In press)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 循環生理学・循環薬理学・分子生物学は重症心不全を救えるか2012

    • Author(s)
      北風政史
    • Journal Title

      呼吸と循環

      Volume: 60

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 心筋症の分類と診断基準2012

    • Author(s)
      朝倉正紀,北風政史
    • Journal Title

      循環器内科

      Volume: 71 Pages: 491-495

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 耐糖能異常は心不全と連関するか?2012

    • Author(s)
      浅沼博司,朝倉正紀,金智隆,北風政史
    • Journal Title

      日本冠疾患学会雑誌

      Volume: 18 Pages: 245-251

    • NAID

      130001928893

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Dipeptidyl-peptidase 4 inhibitor alogliptin attenuates myocardial ischemia/reperfusion infury via an adenosine- dependent mechanism.2014

    • Author(s)
      Ihara M, Yamazaki S, Asanuma H, Kitakaze M.
    • Organizer
      第18回日本心不全学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-10-10 – 2014-10-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] The E3 Ligase Asb2 Regulates Cardiac Development Through Targeting Smad9 for Proteasomal Degradation.2014

    • Author(s)
      Min KD, Asakura M, Ito S, Shirai M, Nakano A, Tsukamoto O, Inoue H, Yamazaki S, Asanuma H, Takashima S, Minamino T, Mochizuki N, Schneider M, Kitakaze M.
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Does the Treatment of Impaired Glucose Tolerance Provide Cardiovascular Benefits in patients with Previous Myocardial Infarction.2014

    • Author(s)
      Kitakaze M, Asakura M, Asanuma H, J-Wind Investigators.
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Exploratory Reserch on Potential Diagnostic as Well as Therapeutic Targets for Heart Failure Using Omics Data Analysis .2014

    • Author(s)
      Asakura M, Asanuma H, Ito S, Min KD, Seguchi O, Takahashi A, Nishigori M, Shindoh K, Imazu M, Nakatani T, Tomonaga T, Minamino N, Kitakaze M.
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Serum Fibroblast Growth Factor 23 as a Surrogate Marker in Patients with Heart Failure.2013

    • Author(s)
      高濱博幸, 今津美樹, 浅沼博司, 舟田晃, 菅野康夫, 大原貴裕, 長谷川拓也, 朝倉正紀, 神崎秀明,安斉俊久, 北風政史
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 次世代シーケンサーを用いた新規心不全関連遺伝子の探索2013

    • Author(s)
      進藤一紘, 朝倉正紀, 閔庚徳, 伊藤慎, 高橋彩子, 今津美樹, 浅沼博司, 北風政史
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] BNPは冠動脈疾患発症リスクの代用マーカーとなりうるか2013

    • Author(s)
      長谷川拓也, 朝倉正紀, 江口和男, 浅沼博司, 天木誠, 高濱博幸, 舟田晃, 菅野康夫, 大原貴裕, 神崎秀明, 橋村一彦, 友池仁遙暢, 金智隆, 安斉俊久, 北風政史
    • Organizer
      第61回日本心臓病学会学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Concept and Consideration for the Clinical Assessment that an AIpha-GI Blocks Cardiac Events in Patients with MI and IGT (ABC Study)2012

    • Author(s)
      Asanuma H, Asakura M, Kim J,Kitakaze M and the ABC Study Investigators.
    • Organizer
      The 33rd Annual Meeting of The Japanese Society of Clinical Pharmacology and Therapeutics
    • Place of Presentation
      沖縄(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Novel synthesized radical-containing nanoparticles augment cardioprotection after ischemiareperfusion injury via nitric oxide in canine hearts2012

    • Author(s)
      Yoshida A, Sanada S, Asanuma H, Sasaki H, Takahama H, Asakura M, Yoshitomi T, Nagasaki Y,Kitakaze M.4
    • Organizer
      European Society of Cardiology Congress 2012.
    • Place of Presentation
      ドイツ・ミュンヘン
    • Related Report
      2012 Annual Research Report
  • [Presentation] Alteration of gene expression profiling of the murine intestine suffering from heart failure.2012

    • Author(s)
      Takahashi A, Asakura M, Min K, Ito S, Shindo K, Yan Y, Liu H, Asanuma H, Mochizuki N,Kitakaze M
    • Organizer
      European Society of Cardiology Congress 2012
    • Place of Presentation
      ドイツ・ミュンヘン
    • Related Report
      2012 Annual Research Report
  • [Book] 再灌流障害と心筋保護 救急医学2014

    • Author(s)
      浅沼博司、伊原まどか、北風政史
    • Total Pages
      124
    • Publisher
      へるす出版
    • Related Report
      2014 Annual Research Report
  • [Book] 内科学第10版2013

    • Author(s)
      浅沼博司、北風政史
    • Total Pages
      2548
    • Publisher
      朝倉書店
    • Related Report
      2013 Annual Research Report
  • [Book] 今日の治療指針20132013

    • Author(s)
      浅沼博司
    • Total Pages
      2064
    • Publisher
      医学書院
    • Related Report
      2013 Annual Research Report
  • [Book] 経静脈治療オーダーマニュアル2012

    • Author(s)
      浅沼博司, 北風政史
    • Total Pages
      764
    • Publisher
      メディカルレビュー社
    • Related Report
      2012 Annual Research Report
  • [Book] 2012-2013 EBM循環器疾患の治療2012

    • Author(s)
      浅沼博司, 北風政史
    • Total Pages
      424
    • Publisher
      中外医学社
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi