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Important roles of non-NO-mediated endothelium-dependent relaxation in cardiovasuclar disease

Research Project

Project/Area Number 16K19383
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionTohoku University

Principal Investigator

Godo Shigeo  東北大学, 医学系研究科, 大学院非常勤講師 (70763233)

Research Collaborator Shimokawa Hiroaki  
Shiroto Takashi  
Saito Hiroki  
Ito Akiyo  
Ikumi Yosuke  
Kajitani Shoko  
Sato Saori  
Lerman Amir  
Eaton Philip  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords血管内皮機能 / 内皮由来弛緩因子 / 内皮由来過分極因子 / 一酸化窒素 / 冠動脈硬化症 / 過酸化水素 / 内皮依存性弛緩反応 / 動脈硬化 / 循環器・高血圧
Outline of Final Research Achievements

This study highlighted that vessel size-dependent contribution of nitric oxide (NO) and endothelium-derived relaxing factor (EDHF) played an important role in coronary microcirculation in mice. Moreover, this study demonstrated that coronary microvascular endothelial dysfunction (CMED) was associated with more advanced plaque characteristics in patients with chest pain and early nonobstructive coronary artery disease, and that CMED was an independent predictor of rupture-prone vulnerable plaques. These results indicate a potential role of CMED in the progression of coronary atherosclerosis in the early stage of the disease.

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会に突入した我が国において心血管病は急速に増加傾向にある。本研究の成果により, 内皮依存性弛緩反応における血管径に応じた一酸化窒素 (NO) と内皮由来過分極因子 (EDHF) の生理的バランスの意義が明らかになり, 特に抵抗血管・微小循環におけるNOを介さない機序での血管恒常性の維持機構を解明することにより, 血管内皮機能と密接な関係にある心血管病の新たな治療戦略を開発に役立つ可能性がある。さらに, NOに依らないEDHFを介した微小循環における血管弛緩反応の重要性に着目している点に独創性と学術的意義がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 14 results)

  • [Int'l Joint Research] Mayo Clinic(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Mayo Clinic(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Important roles of endothelial caveolin-1 in endothelium-dependent hyperpolarization and ischemic angiogenesis in mice2019

    • Author(s)
      Ito Akiyo, Shiroto Takashi, Godo Shigeo, Saito Hiroki, Tanaka Shuhei, Ikumi Yosuke, Kajitani Shoko, Satoh Kimio, Shimokawa Hiroaki
    • Journal Title

      American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 316 Issue: 4 Pages: H900-H910

    • DOI

      10.1152/ajpheart.00589.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Important role of endothelium-dependent hyperpolarization in pulmonary microcirculation in male mice -Implications for hypoxia-induced pulmonary hypertension.2018

    • Author(s)
      ③Shuhei Tanaka, Takashi Shiroto, Shigeo Godo, Hiroki Saito, Yosuke Ikumi, Akiyo Ito, Shoko Kajitani, Saori Sato, and Hiroaki Shimokawa.
    • Journal Title

      American Journal of Physiology. Heart and Circulatory Physiology.

      Volume: - Issue: 5 Pages: H940-H953

    • DOI

      10.1152/ajpheart.00487.2017

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Important role of endothelial caveolin-1 in the protective role of endothelium-dependent hyperpolarization against nitric oxide-mediated nitrative stress in microcirculation in mice2018

    • Author(s)
      Saito H, Godo S, Sato S, Ito A, Ikumi Y, Tanaka S, Ida T, Fujii S, Akaike T, Shimokawa H.
    • Journal Title

      Journal of Cardiovascular Pharmacology

      Volume: 71 Issue: 2 Pages: 113-126

    • DOI

      10.1097/fjc.0000000000000552

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endothelial functions.2017

    • Author(s)
      Shigeo Godo and Hiroaki Shimokawa.
    • Journal Title

      Arteriosclerosis Thrombosis Vascular Biology.

      Volume: 37 Issue: 9

    • DOI

      10.1161/atvbaha.117.309813

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis2017

    • Author(s)
      Shigeo Godo and Hiroaki Shimokawa
    • Journal Title

      Free Radical Biology & Medicine

      Volume: in press Pages: 4-10

    • DOI

      10.1016/j.freeradbiomed.2016.12.019

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Diverse Functions of Endothelial NO Synthases System: NO and EDH2016

    • Author(s)
      Hiroaki Shimokawa and Shigeo Godo
    • Journal Title

      Journal of Cardiovascular Pharmacology

      Volume: 67 Issue: 5 Pages: 361-366

    • DOI

      10.1097/fjc.0000000000000348

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Important roles of endothelial caveolin-1 in endothelium-dependent hyperpolarization and ischemic angiogenesis in mice2019

    • Author(s)
      Ito A, Shiroto T, Godo S, Saito H, Tanaka S, Ikumi Y, Kajitani S, Satoh K, Shimokawa H
    • Organizer
      第83回日本循環器学会学術集会 (2019年3月29-31日, 横浜市)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Important roles of endothelium-dependent hyperpolarization in coronary microcirculation and cardiac diastolic function in mice2019

    • Author(s)
      Ikumi Y, Shiroto T, Kajitani S, Ito A, Tanaka S, Saito H, Godo S, Tsutsui M, Shimokawa H
    • Organizer
      第83回日本循環器学会学術集会 (2019年3月29-31日, 横浜市)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Coronary microvascular endothelial dysfunction is associated with advanced coronary plaque characteristics in patients with early coronary atherosclerosis2019

    • Author(s)
      Shigeo Godo, Michel T Corban, Takumi Toya, Rajiv Gulati, Lilach O Lerman, Amir Lerman
    • Organizer
      American College of Cardiology (ACC) Scientific Session 2019 (2019年3月16-18日, New Orleans, LA, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endothelium-dependent coronary microvascular dysfunction is associated with advanced coronary plaque characteristics in patients with nonobstructive coronary atherosclerosis2019

    • Author(s)
      Shigeo Godo, Michel T Corban, Takumi Toya, Rajiv Gulati, Lilach O Lerman, Amir Lerman
    • Organizer
      American College of Cardiology (ACC) Scientific Session 2019 (2019年3月16-18日, New Orleans, LA, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Coronary microvascular endothelial dysfunction is associated with plaque vulnerability in patients with early coronary atherosclerosis2018

    • Author(s)
      Shigeo Godo, Michel T Corban, Rajiv Gulati, Lilach O Lerman, Amir Lerman
    • Organizer
      American Heart Association (AHA) Scientific Sessions (2018年11月10-12, Chicago, IL, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Coronary microvascular endothelial dysfunction is an independent predictor of larger epicardial plaque area and higher plaque burden2018

    • Author(s)
      Michel T Corban, Shigeo Godo, Rajiv Gulati, Lilach O Lerman, Amir Lerman
    • Organizer
      American Heart Association (AHA) Scientific Sessions (2018年11月10-12, Chicago, IL, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Important role of endothelium-dependent hyperpolarization in ischemic angiogenesis in mice2018

    • Author(s)
      Ito A, Shiroto T, Sato S, Kajitani S, Ikumi Y, Tanaka S, Saito H, Godo S, Shimokawa H
    • Organizer
      American Heart Association (AHA) Scientific Sessions (2018年11月10-12, Chicago, IL, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Important role of neuronal nitric oxide synthase derived endothelium dependent hyperpolarization in coronary microcirculation and cardiac diastolic function in mice2018

    • Author(s)
      Ikumi Y, Shiroto T, Kajitani S, Ito A, Tanaka S, Saito H, Godo S, Tsutsui M, Shimokawa H
    • Organizer
      American Heart Association (AHA) Scientific Sessions (2018年11月10-12, Chicago, IL, USA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肺循環および肺高血圧症における内皮依存性過分極反応の重要性-低酸素誘発性肺高血圧症を中心とした検討-2018

    • Author(s)
      田中修平、白戸崇、神戸茂雄、齊藤大樹、伊藤秋代、井汲陽祐、梶谷翔子、佐藤沙緒里、下川宏明
    • Organizer
      第47回日本心脈管作動物質学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Importance of endothelium-dependent hyperpolarization and oxidative activation of PKG1α in coronary microcirculation in mice.2017

    • Author(s)
      ①Yosuke Ikumi, Shoko Kajitani, Akiyo Ito, Shuhei Tanaka, Hiroki Saito, Shigeo Godo, Takashi Shiroto, and Hiroaki Shimokawa.
    • Organizer
      American Heart Association (AHA) Scientific Sessions
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Importance of Endothelial Dysfunction in the Pathogenesis of Cardiovascular Insufficiency in Metabolic Disorders2017

    • Author(s)
      Shigeo Godo
    • Organizer
      The 81st Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      石川県金沢市
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Physiological Balance between Nitric Oxide and Endothelium-dependent Hyperpolarization Plays Important Roles in Microvascular Homeostasis in Mice2016

    • Author(s)
      Shigeo Godo
    • Organizer
      American Heart Association Scientific Sessions 2016
    • Place of Presentation
      アメリカ合衆国, ニューオリンズ
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Importance of the Physiological Balance between Endothelium-derived Nitric Oxide and Endothelium-dependent Hyperpolarization in Microcirculatory Homeostasis in Mice2016

    • Author(s)
      Shigeo Godo
    • Organizer
      Mechanisms of Vasodilatation 12th International Symposium
    • Place of Presentation
      アメリカ合衆国, ロチェスター
    • Year and Date
      2016-11-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Disruption of Physiological Balance Between Nitric Oxide and Endothelium-Dependent Hyperpolarization Impairs Cardiovascular Homeostasis in Mice2016

    • Author(s)
      Shigeo Godo
    • Organizer
      The 7th Scientific Meeting of Asian Society for Vascular Biology
    • Place of Presentation
      台湾, 花蓮
    • Year and Date
      2016-10-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Physiological balance between nitric oxide and endothelium-dependent hyperpolarization plays important roles in microvascular homeostasis in mice2016

    • Author(s)
      Shigeo Godo
    • Organizer
      The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      宮城県, 仙台市
    • Year and Date
      2016-05-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2022-02-21  

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