Reactive oxygen species as endothelium-derived relaxing factors : Implications and mechanisms.

2010 Fiscal Year Self-evaluation Report

• Project Area: Signaling functions of reactive oxygen species
• Project/Area Number: 20117009
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: SHIMOKAWA Hiroaki Tohoku University, 大学院・医学系研究科, 教授 (00235681)
• Project Period (FY): 2008 – 2012
• Keywords: 活性酵素 / 一酸化窒素合成酵素 / Rho-kinase / メタボリックシンドローム / 臓器関連

Research Abstract

血管内皮は、内皮由来弛緩因子(EDRFs)と総称される数種類の弛緩因子を産生・遊離し、心血管系の恒常性の維持に極めて重要な役割を果たしている。EDRFsの主な因子として、prostaglandin I2(PGI2),一酸化窒素(nitric oxide, NO),内皮由来過分極因子(EDHF)があり、我々はEDHFの本体(の一つ)が内皮から生理的濃度で産生される過酸化水素(H2O2)であることを同定した。また、興味深いことに、内皮NO合成酵素(NOSs)系がNOとH2O2の供給源になっていた。
このような背景を受けて、本研究では、EDRFsとしての活性酸素種(NO,H2O2)の役割と作用機構の解明を目指す。
具体的には、下記の3つの目的を設定した。
研究1:NOSsの血管反応性における生物学的多様性の分子機構の解明
研究2:NOSs/Rho-kinase経路の臓器連関における生物学的多様性の解明
研究3:NOSsの代謝調節における生物学的多様性の解明。

Research Products

• [Journal Article] Long-term treatment with nifedipine suppresses coronary hypercon- stricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo -Possible involve- ment of Rho-kinase pathway- (2011)
  • Author(s): Tsuburaya R, Yasuda S, Shimokawa H., et al.
  • Journal Title: Eur Heart J. in press
  • Peer Reviewed
• [Journal Article] Erythropoietin enhances hydrogen peroxide- mediated dilatation of canine coronary collateral arterioles during myocardial ischemia in dogs in invio. (2010)
  • Author(s): Yada T, Shimokawa H, Hiramatsu O, et al.
  • Journal Title: Am J Physiol. 299 Pages: H1928-H1935
  • Peer Reviewed
• [Journal Article] Combination therapy with olmesartan and azelnidipine improves EDHF-mediated responses in diabetic Apolipoprotein E-deficient mice. (2010)
  • Author(s): Hosoya M, Ohashi J, Shimokawa H.
  • Journal Title: Circ J. 74 Pages: 798-806
  • Peer Reviewed
• [Journal Article] Importance of Rac1 signaling pathway inhibition in the pleiotropic effects of HMG-CoA reductase inhibitors. (2009)
  • Author(s): Rashid M, Tawara S, Shimokawa H.
  • Journal Title: Circ J. 73 Pages: 361-370
  • Peer Reviewed
• [Journal Article] Crucial role of endothelial nitric oxide syntahses systen in endothelium- dependent hyperpolarization in mice. (2008)
  • Author(s): Takaki A, Morikawa K, Shimokawa H.
  • Journal Title: J Exp Med. 205 Pages: 2053-2063
  • Peer Reviewed
• [Presentation] Endothelial research for 25 years : From regenerated endothelium to triple NOSs-deficient mice. (2010)
  • Author(s): Shimokawa H.
  • Organizer: 4^<th> Scientific Meeting of the Asian Society for Vascular Biology
  • Place of Presentation: HK(Invited lecture)
  • Year and Date: 20101120-20101121
• [Book] H2O2が制御する血管弛緩反応の分子機構(谷口直之(編)) (2009)
  • Author(s): 佐藤公雄、下川宏明
  • Total Pages: 2443-2447
  • Publisher: 実験医学