| Project/Area Number |
16K21370
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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 surgery
Drug development chemistry
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| Research Institution | Showa University |
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Principal Investigator |
Mori Yusaku 昭和大学, 医学部, 講師 (90595919)
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| Research Collaborator |
Shimizu Hiroyuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ネスファチン-1 / マウス / 動脈リモデリング / 新生内膜 / 血管内皮細胞 / Nesfatin-1 / 動脈保護 / 摂食抑制ホルモン / 血管形成術 / ペプチド / 血管保護 |
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| Outline of Final Research Achievements |
Nesfatin-1 is a novel anorexic peptide hormone that also induces direct cardiovascular actions. However, it is unclear whether nesfatin-1 can be a therapeutic target for the treatment with cardiovascular diseases because both beneficial and harmful cardiovascular effects of nesfatin-1 are reported in animal models. Here, we evaluated the vasoprotective and vasopressor effects of nesfatin-1 at different doses in mouse models of femoral artery wire injury. Compared with vehicle, nesfatin-1 treatments at 2.0 and 10 μg/kg/day elevated plasma nesfatin-1 levels with no changes in systolic blood pressure. Furthermore, these treatments reduced neointimal hyperplasia without inducing undesirable remodeling in injured arteries. In mice with transgene nucleobindin-2, which is a precursor of nesfatin-1, neointimal area was also lower than those observed in littermate controls. Our findings indicate that nesfatin-1 can be a therapeutic target for improved treatment of peripheral artery disease.
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| Academic Significance and Societal Importance of the Research Achievements |
ネスファチン-1は肥満症治療の創薬ターゲットとして注目されているが、心血管系に対する悪影響を及ぼす懸念があった。本研究から、適切な投与量を選択することでネスファチン-1は心血管系に悪影響を及ぼすことなく、動脈保護作用を示すことが明らかにされた。本研究の結果は、ネスファチン-1が肥満症のみでなく心血管疾患の新たなる治療薬を開発するための手がかりとなる可能性を示している。
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