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Exploratory research for regulatory mechanism underlying vascular neointimal hyperplasia by EDHF

Research Project

Project/Area Number 18K10795
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionNagoya City University (2021)
Nihon Fukushi University (2018-2020)

Principal Investigator

Itoh Takeo  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (70159888)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords内皮依存性膜過分極因子(EDHF) / 動脈グラフト / 異常低血流 / 内膜肥厚 / 血管内皮機能 / 内皮由来弛緩因子(EDNO) / 一酸化窒素(nitric oxide, NO) / Ca2+活性化K+チャネル / 異常血流 / 血管内皮機能障害 / 一酸化窒素(EDNO) / 内皮依存性膜過分極因子 / 一酸化窒素 / Ca活性化K+チャネル / 内皮由来膜過分極因子 / 自家静脈グラフト / 自家動脈グラフト / 血管内膜肥厚
Outline of Final Research Achievements

In terms of use for coronary artery bypass, the patency of artery grafts (such as internal mammary and radial artery grafts) is superior to that of a saphenous vein graft. However, the mechanism underlying this superiority in patency remains to be clarified.
We developed a rabbit model of common carotid artery grafts under poor runoff conditions to examine the effects of surgical operation on the function of endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) in relaxation and vascular remodeling. In such grafts, receptor-activated endothelium-dependent relaxation remained more than 50% and no apparent intimal hyperplasia was present. In contrast with those of rabbit vein grafts in which the functions of EDNO and EDHF are completely lost and display severe intimal hyperplasia. It is suggested that the preserved function of EDNO and EDHF in arterial grafts could be responsible for minimizing intimal hyperplasia in the vascular wall.

Academic Significance and Societal Importance of the Research Achievements

冠動脈、脳動脈や末梢動脈の虚血性疾患において、血流改善のため採取された動脈や静脈を使用したバイパス術がしばしば施行される。この手術では、術後の内膜肥厚による血管閉塞が問題となる。血管内皮細胞はシェアストレス刺激などにより、内皮由来血管弛緩因子(EDNO)や内皮由来過分極因子(EDHF)などの血管弛緩因子を合成・遊離することにより血管の内膜肥厚や狭小化を抑制する。本研究は、低血流環境下において、静脈グラフトに比較して動脈グラフトがより多くのEDNOとEDHFを合成・遊離することにより内膜肥厚を抑制している可能性を明らかにした。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2022 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Reduced function of endothelial nitric oxide and hyperpolarization in artery grafts with poor runoff2022

    • Author(s)
      Masashi Sakakibara, Akio Kodama, Kimihiro Komori, and Takeo Itoh.
    • Journal Title

      J Surg Res

      Volume: 270 Pages: 2-11

    • DOI

      10.1016/j.jss.2021.08.031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ウサギ自家動脈グラフトの内皮依存性弛緩反応におけるTRPV4活性化薬と阻害薬の効果2019

    • Author(s)
      大塚亮,田畑光紀,古森公浩,伊藤猛雄
    • Organizer
      第61回 日本平滑筋学会総会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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