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

• Project/Area Number: 15K08254
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Fukuoka 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: ¥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。

Research Products

• [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
• [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