Mechanism of inhibition of vascular neointimal hyperplasia by oxidative stress responsive factor through functional reguration of vascular progenitor cells
| Project/Area Number |
15K19398
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 動脈硬化 / 酸化ストレス / 血管内膜肥厚 / 血管平滑筋細胞 / アポトーシス / Nrf2/Keap1 / Nrf2 / Keap1 / マクロファージ |
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| Outline of Final Research Achievements |
Abnormal increases in vascular smooth muscle cells (VSMCs) after vascular injury are a key event in the neointimal hyperplasia followed by vascular occlusive diseases. Nrf2/Keap1 system plays a critical role in the oxidative stress response. I have previously found that Nrf2 plays an important role in neointimal hyperplasia after vascular injury. I further demonstrated that TUNEL-positive cells are detected in both the layers of neointima and media, which decreased Keap1 expression, 14 days after vascular injury in mice. Nrf2 deficient mice showed decreased TUNEL-positive cells and enhanced neointimal formation 14 days after vascular injury. In VSMCs, Keap1 depletion increased apoptotic morphological features such as annexin V binding and positive TUNEL staining. Pretransfection of VSMCs with Nrf2 siRNA inhibited apoptosis mediated by Keap1 siRNA. In summary, Keap1-Nrf2 system regulates VSMC apoptosis in the process of neointimal formation, thereby inhibiting VSMC hyperproliferation.
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Report
(4 results)
Research Products
(13 results)
