Effect of protective arm of the renin-angiotensin system on ischemic brain damage

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Ehime University
• Principal Investigator: Iwanami Jun 愛媛大学, 医学系研究科, 准教授 (90624792)
• Co-Investigator(Kenkyū-buntansha): 堀内 正嗣 愛媛大学, 医学系研究科, 教授 (40150338) ; 茂木 正樹 愛媛大学, 医学系研究科, 教授 (20363236) ; 閔 莉娟 愛媛大学, 医学系研究科, 講師 (80726175)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: レニン・アンジオテンシン系 / アンジオテンシンII2型受容体 / 脳血管障害

Outline of Final Research Achievements

Accumulating evidences and previous our research suggest that angiotensin II type 2 receptor(AT2R) stimulation could contribute to protection against ischemic brain damage. However, the effect of ATIP (AT2R interacting protein) on ischemic brain damage is still unclear. Therefore, we investigated the effects of the ATIP on focal cerebral ischemia using ATIP-transgenic (ATIP-Tg) mice. There was no significant difference in ischemic size between WT and ATIP-Tg mice. Treatment with AT2R agonist decreased ischemic size in both strains. Interestingly, this protective effect of AT2R agonist was more marked in ATIP-Tg compared with WT mice. In CBF of core region of ischemic area, there were no significant differences among all groups. However, the reduction of CBF in penumbra region just after MCA occlusion was attenuated in ATIP-Tg mice with AT2R agonist administration. These results suggested that ATIP could enhance the cerebral protective effects of AT2R stimulation after ischemia.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

レニン・アンジオテンシン系のProtective armであるAT2受容体やACE2/Ang(1-7)/Mas系は臓器保護作用が報告されており、その活性化が注目され創薬研究として注目されている。本研究はATIPを分子標的とした独創的な研究でもあり、脳血管障害において、脳梗塞だけでなく、認知症など、さらに将来的には高血圧、糖尿病の病態解明、診断・治療の臨床医学の発展にも寄与する夢のある研究であると考えられる。