2015 Fiscal Year Final Research Report
Development of a novel therapy for atherosclerosis based on alleviation of lipotoxicity of macrophages
| 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)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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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 |
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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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| Free Research Field |
代謝学
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