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Elucidation of the exacerbation mechanisms of ischemic cardiovascular disease induced by testosterone.

Research Project

Project/Area Number 15K10644
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionKinjo Gakuin University (2018)
University of the Ryukyus (2015-2017)

Principal Investigator

SAKANASHI MAYUKO  金城学院大学, 薬学部, 准教授 (80363662)

Co-Investigator(Kenkyū-buntansha) 松崎 俊博  琉球大学, 医学(系)研究科(研究院), 助教 (50244330)
筒井 正人  琉球大学, 医学(系)研究科(研究院), 教授 (70309962)
Research Collaborator NOGUCHI Katsuhiko  
TANIMOTO Akihide  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords一酸化窒素 / テストステロン / 心筋梗塞 / 一酸化窒素合成酵素 / 虚血性心疾患 / 虚血性心血管疾患
Outline of Final Research Achievements

Testosterone is known to have cardiovascular protective effects, however, there have been opposite reports that it aggravates ischemic cardiovascular disease for past few years. To clarify this mechanism, we examined using myocardial infarction developing model mice which lack all nitric oxide synthase isoforms. The major results were as follows; testosterone raised systolic blood pressure with increment of vascular contractility, decreased plasma adiponectin which is involved in regulating glucose levels as well as fatty acid breakdown, increased plasma cholesterols and blood sugar, and so induced cardiovascular death. The findings in this study indicate that the reduced nitric oxide level may contribute to the aggravating effects of testosterone for ischemic cardiovascular disease.

Academic Significance and Societal Importance of the Research Achievements

男性においてテストステロンは、生体内の量的低下が動脈硬化やそれに続く虚血性心疾患を惹起すると考えられており、疾患発症の予防としてテストステロン補充療法に対する期待が寄せられている。しかし、本研究により生体内の一酸化窒素量が減少した状況下においては、テストステロンは心血管傷害作用により、虚血性心血管疾患を増悪化することが示唆された。本研究の成果は、内皮機能の低下などにより一酸化窒素量の減少が予測される高齢男性や、内皮傷害が疑われる男性患者に対して、テストステロン補充療法を行うべきでないという根拠となる点において、大きな学術的意義があると考える。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (9 results)

All 2018 2017

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.2017

    • Author(s)
      Kina-Tanada M, Sakanashi M, Tanimoto A, Kaname T, Matsuzaki T, Noguchi K, Uchida T, Nakasone J, Kozuka C, Ishida M, Kubota H, Taira Y, Totsuka Y, Kina SI, Sunakawa H, Omura J, Satoh K, Shimokawa H, Yanagihara N, Maeda S, Ohya Y, Matsushita M, Masuzaki H, Arasaki A, Tsutsui M.
    • Journal Title

      Diabetologia.

      Volume: 60 Issue: 6 Pages: 1138-1152

    • DOI

      10.1007/s00125-017-4259-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Sex Difference of Cardiovascular Death in the 2/3 Nephrectomized-Nitric Oxide Synthases Deficient Mice: Involvement of Androgen2018

    • Author(s)
      Mayuko Sakanashi, Yuji Taira, Toshihiro Matsuzaki, Junko Nakasone, Haruaki Kubota, Katsuhiko Noguchi, Masato Tsutsui
    • Organizer
      18th World congress of basic and clinical pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 低NO2-/NO3-食の長期的な摂取はメタボリックシンドロームを惹起する2017

    • Author(s)
      坂梨まゆ子、喜名美香、野口克彦、松崎俊彦、仲宗根淳子、平良雄司、久保田陽秋、戸塚裕一、筒井正人
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Research-status Report
  • [Presentation] Pathogenetic roles of the exogenous NO production system in metabolic syndrome, endothelial dysfunction, and cardiovascular death in mice2017

    • Author(s)
      Masato Tsutsui, Mika Kina, Mayuko Sakanashi, Akira Arasaki
    • Organizer
      第90回日本薬理学会
    • Place of Presentation
      長崎新聞文化ホール(長崎県長崎市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 2/3 腎摘 NO 合成酵素完全欠損マウスの突然死における性差2017

    • Author(s)
      坂梨まゆ子、平良雄司、内田太郎、松﨑俊博、野口克彦、仲宗根淳子、下川 宏明、筒井正人
    • Organizer
      第46回日本心脈管作動物質学会
    • Place of Presentation
      琉球大学医学部臨床講義棟(沖縄県西原町)
    • Year and Date
      2017-02-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳梗塞における NO 合成酵素の有害な作用:性差およびテストステロンの関与2017

    • Author(s)
      久保田陽秋、野口克彦、坂梨まゆ子、松﨑俊博、仲宗根淳子、 下川宏明、須加原一博、垣花学、筒井正人
    • Organizer
      第46回日本心脈管作動物質学会
    • Place of Presentation
      琉球大学医学部臨床講義棟(沖縄県西原町)
    • Year and Date
      2017-02-10
    • Related Report
      2016 Research-status Report
  • [Presentation] Sex Difference in Sudden Death of 2/3 Nephrectomized Triple Nitric Oxide Synthases-Deficient Mice.2017

    • Author(s)
      Tsutsui M, Sakanashi M, Taira Y, Matsuzaki T, Noguchi K, Nakasone J, Ohya Y, Shimokawa H
    • Organizer
      The 8th Congress of the International Society for Gender Medicine
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2/3腎摘NO合成酵素完全欠損マウスの突然死における性差2017

    • Author(s)
      筒井正人、坂梨まゆ子、平良雄司、内田太郎、松崎俊博、野口克彦、仲宗根淳子、下川宏明
    • Organizer
      第17回日本NO学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Deleterious effect of all nitric oxide synthases in cerebral infarction in male mice: involvements of sex difference and testosterone.2017

    • Author(s)
      Tsutsui M, Kubota H, Noguchi K, Matsuzaki T, Sakanashi M, Nakasone J, Shimokawa H, Ohya Y, Sugahara K, Kakinohana M
    • Organizer
      American Heart Association Scientific Sessions 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2020-03-30  

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