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Role of changes in the function of G-protein coupled receptors due to cholesterol depletion from the cell membrane in cardiovascular protection

Research Project

Project/Area Number 15K08254
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionFukuoka University

Principal Investigator

Shinichiro Miura  福岡大学, 医学部, 教授 (20343709)

Co-Investigator(Kenkyū-buntansha) 朔 啓二郎  福岡大学, 医学部, 教授 (40183371)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords高血圧 / 脂質 / 循環器 / 循環器・高血圧
Outline of Final Research Achievements

We determined whether changes in the function of angiotensin II type 1 (AT1) receptor receptor due to cholesterol depletion from cardiovascular cell membranes through statin treatment affects blood pressure. Angiotensin II-induced increase in mean blood pressure was significantly suppressed by pretreatment with rosuvastatin in mice. Angiotensin II-induced inositol phosphate production through AT1 receptor was suppressed by cholesterol depletion from cell membranes using rosuvastatin or methyl-beta-cyclodextrin. Angiotensin II-induced activation of AT1 receptor reduced after cholesterol depletion, and this may contribute to blood pressure reduction.

Academic Significance and Societal Importance of the Research Achievements

心血管病は、死亡原因の第2位であり、その克服は非常に重要なテーマである。今回の研究は、その新たな治療法を示唆する基礎研究である。細胞膜が不安定な場合(膜コレステロール含量が減少した場合)には、AT1受容体構造の変化とAng IIが結合可能なAT1受容体発現量の減少が起こり、Ang IIによるIP産生能が低下し、血圧上昇と脈拍数増加が抑制され、心血管保護へ働く可能性が示唆されたとういことである。

Report

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

    (2 results)

All 2016 2015

All Presentation (2 results)

  • [Presentation] Function of G-Protein Coupled Receptors by Cholesterol Depletion from Cell Membrane on Cardiovascular Protection.2016

    • Author(s)
      井手元良彰、三浦伸一郎、後藤昌希、Yuhei,Shiga, 今泉聡、桑野孝志、朔啓二郎
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Role of Changes in the Structure and Function of Angiotensin II Type 1 Receptor Due to Cholesterol Depletion from the Cell Membrane in Cardiovascular Protection.2015

    • Author(s)
      三浦伸一郎
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      松山
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report

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

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