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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390050
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Yamaguchi 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
• Keywords: ホスホランバン / アプタマー / 心筋小胞体 / 心不全治療薬

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.

Research Products

• [Journal Article] Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3 (2013)
  • Author(s): Honda, T., Ishii, A., and Inui, M
  • Journal Title: Am. J. Physiol. Cell Physiol Volume: 304
  • DOI: DOI:10.1152/ajpcell.00343.2012
  • Peer Reviewed
• [Journal Article] Ischemia-reperfusion induces myocardial infarction through mitochondrial Ca^2+ overload (2012)
  • Author(s): Shintani-Ishida, K., Inui, M., and Yoshida, K
  • Journal Title: J. Mol. Cell. Cardiol Volume: 53 Pages: 233-239
  • DOI: DOI:10.1016/j.yjmcc.2012.05.012
  • Peer Reviewed
• [Journal Article] Concise synthesis of 2-benzazepine derivatives and their biological activity (2012)
  • Author(s): So, M., Kotake, T., Matsuura, K., Inui, M., and Kamimura, A
  • Journal Title: J. Org. Chem Volume: 77 Pages: 4017-4028
  • DOI: DOI:10.1021/jo300380z
  • Peer Reviewed
• [Journal Article] Heart failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling (2012)
  • Author(s): Miyazaki, Y., Ikeda, Y., Shiraishi, K., Fujimoto, S. N., Aoyama, H., Yoshimura, K., Inui, M., Hoshijima, M., Kasahara, H., Aoki, H., and Matsuzaki, M
  • Journal Title: PloS one Volume: 7 Pages: e35875
  • DOI: DOI:10.1371/journal.pone.0035875
  • Peer Reviewed
• [Journal Article] Isoform-specific role of protein phosphatase 1 catalytic subunits in sarcoplasmic reticulum-mediated Ca^2+cycling (2011)
  • Author(s): Aoyama, H., Ikeda, Y., Miyazaki, Y., Yoshimura, K., Nishino, S., Yamamoto, T., Yano, Y., Inui, M., Aoki, H., and Matsuzaki, M
  • Journal Title: Cardiovasc. Res Volume: 89 Pages: 79-89
  • DOI: DOI:10.1093/cvr/cvq252
  • 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 Pages: 3269-3277
  • DOI: DOI:10.1091/mbc.E10-02-0117
  • Peer Reviewed
• [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: 特願 2012-028555
  • Filing Date: 2012-02-13