Development of phospholamban aptamer as a novel therapeutic tool for treatment of heart failure

• Project/Area Number: 25870470
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology; Applied pharmacology
• Research Institution: Yamaguchi University
• Principal Investigator: SAKAI Hiroki 山口大学, 医学(系)研究科(研究院), 助教 (40464367)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ホスホランバン / アプタマー / 心不全治療薬 / 細胞膜透過性ペプチド / 核酸アプタマー

Outline of Final Research Achievements

We tried to develop phospholamban aptamer as a novel therapeutic tool for treatment of heart failure. We conjugated the phospholamban RNA aptamer with a cell-penetrating peptide, the modified TAT peptide. This cell-penetrating phospholamban aptamer enhanced contraction/relaxation of isolated adult rat cardiomyocytes as well as corresponding Ca2+ transients. In the mouse heart failure model, the cell-penetrating phospholamban aptamer improved cardiac functions some mice. These results suggested that the cell-panetrating phospholamban aptamer is a potential therapeutic tool for treatment of heart failure.

Research Products

• [Journal Article] Signaling mechanism underlying the promotion of keratinocyte migration by angiotensin II (2015)
  • Author(s): Hiroki Sakai, Kenji Matsuura, Yoshie Tanaka, Takeshi Honda, Teruo Nishida, Makoto Inui
  • Journal Title: Molecular Pharmacology Volume: 87 Issue: 2 Pages: 277-285
  • DOI: 10.1124/mol.114.096461
  • Peer Reviewed
• [Journal Article] A cell-penetrating phospholamban-specific RNA aptamer enhances Ca2+ transients and contractile function in cardiomyocytes. (2014)
  • Author(s): Sakai, H., Ikeda, Y., Honda, T., Tanaka, Y., Shiraishi, K., and Inui, M.
  • Journal Title: J. Mol. Cell. Cardiol. Volume: 76 Pages: 177-185
  • DOI: 10.1016/j.yjmcc.2014.09.006
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Enhancement of Ca2+ transient and contractile function of cardiomyocytes by phospholamban specific RNA aptamer (2015)
  • Author(s): 酒井大樹、池田安宏、本田健、田中貴絵、白石宏造、乾誠
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] ホスホランバンアプタマーによる心筋収縮能およびCa2+トランジェントの増強作用 (2014)
  • Author(s): 酒井大樹、池田安宏、本田健、田中貴絵、白石宏造、乾誠
  • Organizer: 第67回日本薬理学会西南部会
  • Place of Presentation: 産業医科大学（福岡県・北九州市）
  • Year and Date: 2014-11-23
• [Presentation] Promotion of endothelial cell migration and tube formation by SEK-1005 (2014)
  • Author(s): 酒井大樹、中島 京、岩田博夫、乾 誠
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター（宮城県）
• [Presentation] SEK-1005による血管内皮細胞の遊走及び管腔形成促進効果
  • Author(s): 酒井大樹、中島 京、岩田博夫、乾 誠
  • Organizer: 第23回日本循環薬理学会
  • Place of Presentation: 福岡大学メディカルホール（福岡県）