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Development of a novel inotropic and lucitorpic agent for treatment of heart failure

Research Project

Project/Area Number 22390050
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionYamaguchi University

Principal Investigator

INUI Makoto  山口大学, 大学院・医学系研究科, 教授 (70223237)

Co-Investigator(Kenkyū-buntansha) HONDA Takeshi  山口大学, 大学院・医学系研究科, 講師 (30457311)
KURAMASU Atsuo  山口大学, 大学院・医学系研究科, 准教授 (90302091)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsホスホランバン / アプタマー / 心筋小胞体 / 心不全治療薬 / カルシウム輸送 / 強心薬
Research Abstract

We developed a phospholamban specific RNA aptamer as a novel inotropic and lucitropic agent to treat heart failure. The obtained aptamer increased Ca2+ uptake by cardiac sarcoplasmic reticulum in the nanomolar range. To introduce it into cardiomyocytes, we conjugated a membrane penetrating peptide to the aptamer. This aptamer facilitated contraction as well as relaxation of isolated cardiomyocytes. Furthermore, the aptamer improved cardiac functions in vivo. A membrane penetrating peptide-conjugated phospholamban aptamer is thus a potent inotropic and lucitropic agent and could be a novel drug for heart failure.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (11 results)

All 2013 2012 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN32013

    • Author(s)
      Honda, T., Ishii, A., and Inui, M
    • Journal Title

      Am. J. Physiol. Cell Physiol

      Volume: 304 Issue: 11 Pages: C1091-C1097

    • DOI

      10.1152/ajpcell.00343.2012

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ischemia-reperfusion induces myocardial infarction through mitochondrial Ca^2+ overload2012

    • Author(s)
      Shintani-Ishida, K., Inui, M., and Yoshida, K
    • Journal Title

      J. Mol. Cell. Cardiol

      Volume: 53 Issue: 2 Pages: 233-239

    • DOI

      10.1016/j.yjmcc.2012.05.012

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Concise synthesis of 2-benzazepine derivatives and their biological activity2012

    • Author(s)
      So, M., Kotake, T., Matsuura, K., Inui, M., and Kamimura, A
    • Journal Title

      J. Org. Chem

      Volume: 77 Issue: 8 Pages: 4017-4028

    • DOI

      10.1021/jo300380z

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heart Failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling2012

    • Author(s)
      Yosuke Miyazaki
    • Journal Title

      PLOS ONE

      Volume: 7 Issue: 4 Pages: 35875-35875

    • DOI

      10.1371/journal.pone.0035875

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-specific roles of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca(2+) cycling2011

    • Author(s)
      Hidekazu Aoyama
    • Journal Title

      Cardiovasc Res

      Volume: 89 Issue: 1 Pages: 79-88

    • DOI

      10.1093/cvr/cvq252

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-specific role of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca^<2+> cycling2011

    • Author(s)
      Hidekazu Aoyama
    • Journal Title

      Cardiovascular Research

      Volume: 89 Pages: 78-88

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PDZRN3 negatively regulates BMP-2-induced osteoblast differentiation through inhibition of Wnt signaling.2010

    • Author(s)
      Honda, T., Yamamoto, H., Ishii, A., and Inui, M.
    • Journal Title

      Mol. Biol. Cell

      Volume: 21 Issue: 18 Pages: 3269-3277

    • DOI

      10.1091/mbc.e10-02-0117

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] PDZRN3 negatively regulates BMP-2-induced osteoblast differentiation through inhibition of Wnt signaling.2010

    • Author(s)
      Takeshi Honda
    • Journal Title

      Molecular Biology of the Cell

      Volume: 21 Pages: 3269-3277

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] RNA aptamers against phospholamban with improved stability and efficacy2012

    • Author(s)
      Yoshie Tanaka, et al
    • Organizer
      日本薬理学会
    • Place of Presentation
      国際会議場京都市
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] ホスホランバン標的修飾RNAアプタマー2012

    • Inventor(s)
      乾 誠、田中貴絵、酒井大樹、池田安宏、松崎益徳
    • Industrial Property Rights Holder
      山口大学
    • Industrial Property Number
      2012-028555
    • Filing Date
      2012-02-13
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] ホスホランバン標的修飾RNAアプタマー2012

    • Inventor(s)
      乾誠
    • Industrial Property Rights Holder
      山口大学
    • Industrial Property Number
      2012-028555
    • Filing Date
      2012-02-13
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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