| Project/Area Number |
23249038
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIDA Ken-ichi 東京大学, 医学(系)研究科(研究院), 教授 (40166947)
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| Co-Investigator(Kenkyū-buntansha) |
MORIMOTO Keiko 奈良女子大学, 生活環境学部, 教授 (30220081)
KUREBAYASHI Nagomi 順天堂大学, 医学部, 教授 (50133335)
UEYAMA Takashi 和歌山県立医科大学, 医学部, 准教授 (50264875)
KUWAHIRA Ichiro 東海大学, 医学部, 教授 (60186567)
SHIRAI Mikiyasu 国立循環器病研究センター, 心臓生理機能部, 部長 (70162758)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥49,790,000 (Direct Cost: ¥38,300,000、Indirect Cost: ¥11,490,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2012: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2011: ¥33,800,000 (Direct Cost: ¥26,000,000、Indirect Cost: ¥7,800,000)
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| Keywords | 睡眠時無呼吸症候群 / 間歇低酸素暴露 / 心不全 / 肺高血圧 / オートファジー / 一酸化窒素 / アルギナーゼ / 間歇低酸素 / 高血圧 / 加齢 / 虚血 / 閉経 / 間歇的低酸素 / 心機能障害 / 性差医学 / 歯学 / 認知機能障害 / 低酸素 / ユビキチン化 / β-アドレナリン受容体 |
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| Research Abstract |
We have exploited apparatus that can expose many rats to intermittent hypoxia (IH) for a long period. IH for 3 weeks induces autophagy in the myocardium of the young rats, thereby preventing heart failure through degradation of injured organnels and degenerated proteins.
In adult (9 month) but not young (2 month) rats, IH for 3 weeks induces pulmonary artery (PA) hypertension (PAH) through activation of arginase and reciprocal inhibition of nitric oxide (NO) synthase (NOS). In young rats, IH for 6 weeks induces recruitement of macrophage with enhanced expression of beta3-adrenergic receptor-inducible NOS around PAs. With sympathetic overdrive, the macrophage-derived NO prevents PAH. In young rats fed high fat diet, IH for 4-5days induced PAH through activation of endothelin or coagulation systems. Collectively, IH induces adaptative mechanisms to prevent heart failure or PAH in young and healthy arts, but IH exerts deleterious effects in adult and hyperlipidemic rats.
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