| Project/Area Number |
24790930
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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 |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
ISHII Norio 熊本大学, 医学部附属病院, 助教 (10599111)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | マクロファージ / AMPK / 動脈硬化 / 細胞周期 |
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| Research Abstract |
In this study, we investigated whether activation of AMP-activated protein kinase (AMPK) could suppress macrophage proliferation, using AICAR, which is a pharmacological AMPK activator. AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest. Moreover, treatment with AICAR suppressed atherosclerotic lesion formation, and decreased the number of PCNA-positive macrophages in apolipoprotein E-deficient mice. In conclusion, we found that AICAR-mediated AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest, and suppressed the progression of atherosclerosis in apolipoprotein E-deficient mice. Because the proliferation of vascular cells including macrophages is a key event in the development and progression of atherosclerosis, these effects of AMPK activation may represent therapeutic targets for atherosclerosis.
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