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

2017 Fiscal Year Final Research Report

• 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
• Keywords: 高血圧 / 脂質

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.

Free Research Field

循環器

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。