| Project/Area Number |
25293213
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAGASHIMA SHUICHI 自治医科大学, 医学部, 講師 (30406136)
TAKAHASHI MANABU 自治医科大学, 医学部, 講師 (70406122)
YAMAMURO DAISUKE 自治医科大学, 医学部, リサーチレジデント (20739255)
坂井 謙斗 自治医科大学, 医学部, ポストドクター (30646352)
大須賀 淳一 自治医科大学, 医学部, 准教授 (10334400)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 動脈硬化 / 泡沫細胞 / マクロファージ / コレステロール / リパーゼ / トランスジェニック / マウス / 小胞体ストレス / オキシステロール / 酵素 / 加水分解 / 脂肪酸 / 小胞体 / アポトーシス / エステル |
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| Outline of Final Research Achievements |
Foam cells in atheromatous lesions are characterized by macrophages loaded with cholesteryl ester in lipid droplets. The cellular CE is hydrolyzed not only by hormone-sensitive lipase (Lipe) but also by neutral CE hydrolase 1 (NCEH1), which we identified as a unique CE hydrolase functional in human and murine macrophages. It is plausible that overexpression of NCEH1 in macrophages is protective against atherosclerosis not only by reducing the burden of CE, but also alleviating other immunological lipotoxicity. To test these hypotheses, we have generated mice overexpoessing Nceh1 or Lipe in a macrophage-specific manner using Cre/lox technology. The peritoneal macrophages expressed 3-fold higher levels of mRNA compared with those from wild-type mice. We are going to examine the effects of the transgene on the development of atherosclerosis.
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