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A Study for Epigenetic Regulation to Maintain Cardiac Homeostasis

Research Project

Project/Area Number 21689022
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

ASANO Yoshihiro  大阪大学, 大学院・医学系研究科, 助教 (60527670)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2010: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords分子心臓病態学 / エピゲノム / ヘテロクロマチン / クロマチン免疫沈降法 / 胎児性遺伝子 / ヒストン修飾 / ピストン修飾
Research Abstract

Sustained gene activation, such as" cardiac fetal gene reactivation", has an important role in the mechanism underlying exacerbations of chronic heart failure. However, the maintenance mechanism of its expressional activation has not yet been fully elucidated. We first found evidence for heterochromatin disruption in the nucleus of failing cardiomyocytes and paradoxical depression of cis-acting transcription factors, despite elevated levels of target cardiac fetal genes, suggesting that epigenetic gene regulation might be involved in this phenomenon. In addition, we newly developed in vivo chromatin immunoprecipitation assay, which has hardly been applied in the field of cardiac tissue. The proven alteration in transcriptional sensitivity by epigenetic gene modification was found to play a significant role in the" nuclear memory" mediating heart failure, raising the hope for the novel pathological understanding for chronic diseases.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (32 results)

All 2012 2011 2010 2009

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (6 results) Book (8 results)

  • [Journal Article] Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer2011

    • Author(s)
      Nishikawa K, Asai T, Shigematsu H, Shimizu K, Kato H, Asano Y, Takashima S, Mekada E, Oku N, Minamino T
    • Journal Title

      J Control Release

      Volume: (in press)

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A case of non-cardiogenic acute pulmonary edema in a patient with POEMS syndrome-associated pulmonary arterial hypertension2011

    • Author(s)
      Hara M, Mizote I, Nakaoka Y, Tanaka H, Asano Y, Sakata Y, Komuro I
    • Journal Title

      Ann Hematol

      Volume: 90(4) Pages: 489-90

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The impact of cardiac resynchronization therapy in an end-stage heart failure patient with a left ventricular assist device as a bridge to recovery. A case report2011

    • Author(s)
      Muratsu J, Hara M, Mizote I, Asano Y, Sakata Y, Saito S, Matsumiya G, Sawa Y, Komuro I
    • Journal Title

      Int Heart J

      Volume: 52(4) Pages: 246-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical impact of off-label cardiac resynchronization therapy in end-stage heart failure patients on continuous intravenous inotrope2011

    • Author(s)
      Hara M, Mizuno H, Mizote I, Nakatani D, Asano Y, Sakata Y, Nanto S, Komuro I
    • Journal Title

      Clin Cardiol

      Volume: 34(11) Pages: 714-20

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Impact of Cardiac Resynchronization Therapy in an End-Stage Heart Failure Patient With a Left Ventricular Assist Device as a Bridge to Recovery A Case Report2011

    • Author(s)
      Muratsu J, Hara M, Mizote I, Asano Y, Sakata Y, Saito S, Matsumiya G, Sawa Y, Komuro I
    • Journal Title

      International Heart Journal

      Volume: 52 Issue: 4 Pages: 246-247

    • DOI

      10.1536/ihj.52.246

    • NAID

      130000971171

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation2010

    • Author(s)
      Nakano A, Kato H, Watanabe T, Min KD, Yamazaki S, Asano Y, Seguchi O, Higo S, Shintani Y, Asanuma H, Asakura M, Minamino T, Kaibuchi K, Mochizuki N, Kitakaze M, Takashima S
    • Journal Title

      Nature Cell Biology

      Volume: 12(6) Pages: 583-90

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1(HP1)2010

    • Author(s)
      Higo S, Asano Y, Kato H, Yamazaki S, Nakano A, Tsukamoto O, Seguchi O, Asai M, Asakura M, Asanuma H, Sanada S, Minamino T, Komuro I, Kitakaze M, Takashima S
    • Journal Title

      J Biol Chem

      Volume: 285(41) Pages: 31337-47

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/ CRE-like element in cardiomyocytes2010

    • Author(s)
      Sawada T, Minamino T, Fu HY, Asai M, Okuda K, Isomura T, Yamazaki S, Asano Y, Okada K, Tsukamoto O, Sanada S, Asanuma H, Asakura M, Takashima S, Kitakaze M, Komuro I
    • Journal Title

      J Mol Cell Cardiol

      Volume: 48(6) Pages: 1280-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of C/ EBP Homologous Protein Attenuates Endoplasmic Reticulum-Mediated Apoptosis and Cardiac Dysfunction Induced by Pressure Overload2010

    • Author(s)
      Fu HY, Okada KI, Liao Y, Tsukamoto O, Isomura T, Asai M, Sawada T, Okuda K, Asano Y, Sanada S, Asanuma H, Asakura M, Takashima S, Komuro I, Kitakaze M, Minamino T
    • Journal Title

      Circulation

      Volume: 122(4) Pages: 361-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sildenafil and steroid therapy effectively improved POEMS syndromeassociated pulmonary arterial hypertension2010

    • Author(s)
      Shimomura Y, Hara M, Mizote I, Nakaoka Y, Tanaka H, Asano Y, Sakata Y, Komuro I
    • Journal Title

      Int J Hematol

      Volume: 92(5) Pages: 774-6

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1 (HP1).2010

    • Author(s)
      Higo S, et al.
    • Journal Title

      J Biol Chem.

      Volume: 285 Pages: 31337-47

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation.2010

    • Author(s)
      Nakano A, et al.
    • Journal Title

      Nature Cell Biology.

      Volume: 12 Pages: 583-590

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of C/EBP homologous protein attenuates endoplasmic reticulum-mediated apoptosis and cardiac dysfunction induced by pressure overload.2010

    • Author(s)
      Fu HY, et al.
    • Journal Title

      Circulation.

      Volume: 122 Pages: 361-369

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/CRE-like element in cardiomyocyte2010

    • Author(s)
      Sawada T, et al.
    • Journal Title

      J Mol Cell Cardiol. (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure2009

    • Author(s)
      Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M
    • Journal Title

      J Am Coll Cardiol

      Volume: 53(22) Pages: 2070-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] PKA rapidly enhances proteasome assembly and activity in in vivo canine hearts2009

    • Author(s)
      Asai M, Tsukamoto O, Minamino T, Asanuma H, Fujita M, Asano Y, Takahama H, Sasaki H, Higo S, Asakura M, Takashima S, Hori M, Kitakaze M
    • Journal Title

      J Mol Cell Cardiol

      Volume: 46(4) Pages: 452-62

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure.2009

    • Author(s)
      Tsukamoto O, et al.
    • Journal Title

      J Am Coll Cardiol. 53

      Pages: 2070-2077

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PKA rapidly enhances proteasome assembly and activity in in vivo canine hearts.2009

    • Author(s)
      Asai M, et al.
    • Journal Title

      J Mol Cell Cardiol. 46

      Pages: 452-462

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Evidence for dynamic changes of chromatin state at the stress-induced gene locus in cardiomyocytes2011

    • Author(s)
      Shuichiro Higo, Yoshihiro Asano, Seiji Takashima, Issei Komuro
    • Organizer
      Molecular Cardiovascular Conference
    • Place of Presentation
      北海道
    • Year and Date
      2011-09-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心不全におけるクロマチンリモデリング制御と細胞機能維持機構の解明、成人病の病因・病態の解明に関する研究助成2011

    • Author(s)
      朝野仁裕
    • Organizer
      第17回研究発表会
    • Place of Presentation
      大阪
    • Year and Date
      2011-07-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 心不全におけるクロマチンリモデリング制御と細胞機能維持機構の解明2011

    • Author(s)
      朝野仁裕
    • Organizer
      成人病の病因・病態の解明に関する研究助成第17回研究発表会
    • Place of Presentation
      大阪
    • Year and Date
      2011-07-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心不全の新しい病態解析法新しい心筋viability評価法の開発による治療抵抗性心不全へのアプローチ2011

    • Author(s)
      朝野仁裕
    • Organizer
      大阪ハートクラブ学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2011-05-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 心不全の新しい病態解析法新しい心筋viability評価法の開発による治療抵抗性心不全へのアプローチ2011

    • Author(s)
      朝野仁裕
    • Organizer
      大阪ハートクラブ
    • Place of Presentation
      大阪
    • Year and Date
      2011-05-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] Heterochromatin Protein 1 Acts as an Intra-nuclear Redox Sensor2010

    • Author(s)
      Higo S, et al.
    • Organizer
      American Heart Association Scientific Sessions 2010
    • Place of Presentation
      アメリカ、シカゴ
    • Year and Date
      2010-11-16
    • Related Report
      2010 Annual Research Report
  • [Book] 心不全の原因・病態に迫る検査「遺伝子診断はどのような症例に行うべきか?」変貌する心不全診療2012

    • Author(s)
      朝野仁裕
    • Publisher
      南光堂
    • Related Report
      2011 Final Research Report
  • [Book] 心不全の原因診断の進歩、心不全2012

    • Author(s)
      朝野仁裕、小室一成
    • Publisher
      診断と治療社
    • Related Report
      2011 Final Research Report
  • [Book] 拡張型心筋症に関する新しい解析方法、CARDIAC PRACTICE2011

    • Author(s)
      朝野仁裕
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Final Research Report
  • [Book] 最新・心不全Update-研究と臨床の最前線、心不全の先端的研究トピックス、心不全のジェネティクスとエピジェネティクス、医学のあゆみ2010

    • Author(s)
      朝野仁裕、小室一成
    • Publisher
      医歯薬出版
    • Related Report
      2011 Final Research Report
  • [Book] 心不全におけるクロマチンリモデリングの役割、Annual Review循環器2010

    • Author(s)
      朝野仁裕
    • Publisher
      中外医学社
    • Related Report
      2011 Final Research Report
  • [Book] 医学の歩み 心不全-研究と臨床の最前線 1月第5曜特集号2010

    • Author(s)
      朝野仁裕、小室一成
    • Total Pages
      7
    • Publisher
      医歯薬出版社
    • Related Report
      2009 Annual Research Report
  • [Book] Annual Review 2010循環器2010

    • Author(s)
      朝野仁裕
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2009 Annual Research Report
  • [Book] Altered epigenetic memory with chromatin disruption in the end-stage failing heart.分子心血管病2009

    • Author(s)
      朝野仁裕
    • Publisher
      先端医学社
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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