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Novel heart failure pharmacotherapy that targets nuclear signaling pathway in cardiac myocytes

Research Project

Project/Area Number 15K09108
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center

Principal Investigator

HASEGAWA Koji  独立行政法人国立病院機構(京都医療センター臨床研究センター), 展開医療研究部, 研究部長 (50283594)

Research Collaborator MORIMOTO Tatsuya  静岡県立大学
SUNAGAWA Yoichi  静岡県立大学
KATANASAKA Yasufumi  静岡県立大学
MIYAZAKI Yusuke  静岡県立大学
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords循環器・高血圧 / シグナル伝達 / 薬学 / トランスレーショナルリサーチ
Outline of Final Research Achievements

Heart failure is a leading cause of cardiovascular death. During development and deterioration of heart failure, cardiomyocytes undergo maladaptive hypertrophy, accompanied by re-induction of the fetal gene program. The transcriptional coactivator p300, an intrinsic histone acetyltransferase (HAT), is an important factor involved in the regulation of gene expression during cardiomyocyte hypertrophy. The natural compound, curcumin, possesses p300-specific HAT inhibitory activity. Our previous study demonstrated that curcumin prevents the development of cardiac hypertrophy by inhibiting p300-HAT activity. Here, we showed that demethoxycurcumin and bisdemethoxycurcumin, other major curcuminoids isolated from Curcuma longa, inhibited p300-HAT activity and cardiomyocyte hypertrophy to almost the same extent as curcumin. Thus, structural differences among the three compounds may not be involved in the inhibitory effects on p300-HAT activity and cardiac hypertrophy.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2017 2016 2015

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 11 results)

  • [Journal Article] MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol.2016

    • Author(s)
      Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K.
    • Journal Title

      Circ Res.

      Volume: - Issue: 5 Pages: 835-847

    • DOI

      10.1161/circresaha.116.309528

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD2016

    • Author(s)
      Funamoto M, Sunagawa Y, Katanasaka Y, Miyazaki Y, Imaizumi A, Kakeya H, Yamakage H, Satoh-Asahara N, Komiyama M, Wada H, Hasegawa K, Morimoto T.
    • Journal Title

      International Journal of Chronic Obstructive Pulmonary Disease

      Volume: 11 Pages: 2029-2034

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tyrosine phosphorylation of RACK1 triggers cardiomyocyte hypertrophy by regulating the interaction between p300 and GATA4.2016

    • Author(s)
      Suzuki H, Katanasaka Y, Sunagawa Y, Miyazaki Y, Funamoto M, Wada H, Hasegawa K, Morimoto T.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1862 Pages: 1544-1557

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Statins on Atherogenic Serum Amyloid A and α1-Antitrypsin Low-Density Lipoprotein Complexes2016

    • Author(s)
      Miyazaki Y, Katanasaka Y, Sunagawa Y, Sae Hirano-Sunagawa, Funamoto M, Eriko Morimoto, Komiyama M, Shimatsu A, Satoh-Asahara N, Yamakage H, Wada H, Hasegawa K, Morimoto T.
    • Journal Title

      International Journal of Cardiology

      Volume: 3 Pages: 332-336

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Analysis of GATA4 Complex, a Cardiac Hypertrophy-response Transcriptional Factor, Using a Proteomics Approach.2016

    • Author(s)
      Sunagawa Y, Katanasaka Y, Wada H, Hasegawa K, Morimoto T
    • Journal Title

      Yakugaku Zasshi

      Volume: 136(2) Pages: 151-6

    • NAID

      130005121459

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Analysis on Time Course Changes of Adipocytokine Levels and Abdominal Obesity after Quitting Smoking2017

    • Author(s)
      Maki Komiyama, Hiromichi Wada, Hajime Yamakage, Noriko Asahara, Sayaka Shimada, Akira Shimatsu, Tatsuya Morimoto, Yuko Takahashi, Koji Hasegawa
    • Organizer
      American Heart Association EPI/LIFESTYLE 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Quitting Smoking Reduces Lectin-like low- density lipoprotein receptor-1 index, an Independent Cardiovascular Risk Marker of Vascular Inflammation2017

    • Author(s)
      Maki Komiyama, Hiromichi Wada, Hajime Yamakage, Noriko Asahara, Sayaka Shimada, Masaharu Akao, Tatsuya Morimoto, Yuko Takahashi, Tatsuya Sawamura, Koji Hasegawa
    • Organizer
      American Heart Association EPI/LIFESTYLE 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Histone Acetylation Domain by p300 are Changed During the Transition From Cardiac Hypertrophy to Heart Failure Circulation. 2017;136:A18911. (Abstract 18911)2017

    • Author(s)
      Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Hiromichi Wada, Koji Hasegawa and Tatsuya Morimoto
    • Organizer
      American Heart Association Scientific Sessions 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Statins reduced atherogenic oxidatively modified low-density lipoprotein complexes: STAT-LVDF study2016

    • Author(s)
      Yusuke Miyazaki, Yasufumi Katanasaka, Yoichi Sunagawa, Masafumi, Funamorto, Hidetoshi Suzuki, Hiromichi Wada, Noriko Asahara, Akira Shimatsu, Hajime Yamakage, Koji Hasegawa, and Tatsuya Morimoto
    • Organizer
      International Society of Cardiomyopathies and Heart Failure Congress 2016
    • Place of Presentation
      Kyoto
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nobiletin, a polymethoxy flavonoid, prevents pressure-overload-induced systolic dysfunction in mice2016

    • Author(s)
      Yoichi Sunagawa, Shintaro Ogawahara, Anna Suzuki, Masafumi Funamoto, Ryoga Sakurai, Yasufumi Katanasaka, Tomohiro Asakawa, Toshiyuki Kan, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      International Society of Cardiomyopathies and Heart Failure Congress 2016
    • Place of Presentation
      Kyoto
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epigenetic Histone Acetylation by p300 are changed from Cardiac Hypertrophy to Heart Failure2016

    • Author(s)
      Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Kana Shimizu, Yusuke Miyazaki, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      International Society of Cardiomyopathies and Heart Failure Congress 2016
    • Place of Presentation
      Kyoto
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protein Arginine Methyltransferase 5/Methylosome Protein 50 Complex Inhibits p300 Histone Acetyltransferase Activity and Hypertrophic Gene transcription in Cultured Cardiomyocytes2015

    • Author(s)
      Yusuke Miyazaki, Yasufumi Katanasaka, Yoichi Sunagawa, Hiromichi Wada, Koji Hasegawa and Tatsuya Morimoto
    • Organizer
      AHA Scientific Sessions 2015
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of Novel Target Molecules of Nobiletin, a Potent Therapeutic Agent Against Heart Failure2015

    • Author(s)
      Yoichi Sunagawa, Kehima Hieda, Ryoga Sakurai, Shintaro Ogawahara, Yasufumi Katanasaka, Tomohiro Asakawa, Toshiyuki Kan, Akira Murakami, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      AHA Scientific Sessions 2015
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A Transcriptional Co-activator, p300 is Involved in the Epigenetic Gene Activation on Hypertrophic Response Gene Promoters during Cardiomyocyte Hypertrophy2015

    • Author(s)
      Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Hiromichi Wada、Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      19th Annual Scientific Meeting of the ISCP
    • Place of Presentation
      Buenos Aires,Argentina
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A LIPOPHILIC PITAVASTATIN SUPPRESSES CELL HYPERTROPHY IN CULTURED CARDIOMYOCYTES2015

    • Author(s)
      Yasufumi Katanasaka, Sae Hirano, Yoichi Sunagawa, Ryoga Sakurai, Hidetoshi Suzuki, Hiromichi Wada, Akira Shimatsu, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      Asian Pacific Society of Cardiology Congress 2015
    • Place of Presentation
      Abu Dhabi, UAE
    • Year and Date
      2015-04-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] MEP50 RECRUITS PRMT5 TO p300 AND SUPRESSES p300/GATA4-INDUCED HYPERTROPHIC GENE TRANSCRIPTION2015

    • Author(s)
      Hiroki Wakabayashi, Yasufumi Katanasaka, Yusuke Miyazaki, Ryoga Sakurai, Yoichi Sunagawa, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      Asian Pacific Society of Cardiology Congress 2015
    • Place of Presentation
      Abu Dhabi, UAE
    • Year and Date
      2015-04-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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