| Project/Area Number |
23591102
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
YAMAMOTO Koichi 大阪大学, 医学(系)研究科(研究院), 講師 (00528424)
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| Co-Investigator(Kenkyū-buntansha) |
楽木 宏実 (樂木 宏実) 大阪大学, 大学院医学系研究科 老年・腎臓内科学, 教授 (20252679)
大石 充 鹿児島大学, 大学院 医歯学総合研究科 心臓血管・高血圧内科学, 教授 (50335345)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 酸化LDL受容体 / アンジオテンシンII受容体 / 細胞内シグナル / 動脈硬化 / 酸化LDL / アンジオテンシンII / G蛋白共役型受容体 / 細胞内シグナル伝達経路 / Angiotensin II受容体 / 複合体形成 / Angiotensin II 受容体 |
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| Research Abstract |
In this study, we investigated our hypothesis that the angiotensin II type 1 receptor (AT1) is involved in the oxidized LDL (oxLDL)-induced vascular responses involved in the pathogenesis of cardiovascular disease. We found that both the lectin like oxLDL receptor (LOX-1) and AT1 are required for the ability of oxLDL to activate cell signaling and that LOX-1 and AT1 form receptor complexes on cell surface membranes. Mutations in AT1 greatly reduced the capacity of oxLDL to activate G protein and MAP kinase. In addition, oxLDL induced acute blood pressure elevations in mice and these hypertensive effects were totally abolished by deletion of AT1a or LOX-1. In addition, oxLDL-induced impairment of endothelial-dependent vascular relaxation was abolished by ARB or genetic deletion of AT1 in mice. These findings indicate that oxLDL-induced activation of AT1 constitutes a heretofore unrecognized mechanism that could further contribute to the effects of oxLDL on risk for atherosclerosis.
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