| Project/Area Number |
23591101
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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 | Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses (2013)
Osaka University (2011-2012) |
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Principal Investigator |
KURODA TADASHI 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), その他部局等, その他(副部長) (60403078)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAOKA Yoshikazu 大阪大学, 医学(系)研究科(研究院), 助教 (90393214)
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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 |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 動脈硬化 / 血管炎症 / 内皮 / Gab1 / KLF2 / トランスジェニックマウス / KLF4 |
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| Research Abstract |
We reported that Gab1 is essential for postnatal angiogenesis through the analysis of endothelium-specific Gab1 knockout (Gab1ECKO) mice. However, the role of Gab1 in atherosclerosis remains unknown. We intercrossed Gab1ECKO mice with ApoE knockout (ApoEKO) mice. Six-month-old male ApoEKO/Gab1ECKO and littermate control (ApoEKO) mice were treated with angiotensin II (AngII) via an osmotic infusion minipump. After AngII treatment, ApoEKO/Gab1ECKO mice showed significantly enhanced atherosclerosis and aneurysm formation compared with control mice. The production of proinflammatory cytokines in the aorta was significantly enhanced in ApoEKO/Gab1ECKO mice compared with control. The expression levels of KLF2 and KLF4 were significantly reduced in the aortic endothelium of ApoEKO/Gab1ECKO mice compared with control. Collectively, endothelial Gab1 deletion accelerates AngII-dependent vascular inflammation and atherosclerosis presumably via downregulation of KLF2 and KLF4.
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