A study of the role of cytokines in the development of atherosclerosis using double knockout mice
| Project/Area Number |
11671111
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Gifu University |
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Principal Investigator |
WADA Hisayasu (2000) Gifu Univ.School of Med. ; Research Associate, 医学部, 助手 (10283300)
藤井 秀比古 (1999) 岐阜大学, 医学部, 助手 (50301213)
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| Co-Investigator(Kenkyū-buntansha) |
SEISHIMA Mitsuru Gifu Univ.School of Med. ; Professor, 医学部, 教授 (10171315)
SAITO Kuniaki Gifu University Hospital ; Assistant professor, 医学部・附属病院, 講師 (80262765)
YAMADA Yasuhiro Gifu Univ.School of Med. ; Research Associate, 医学部, 助手 (10324295)
SEKIKAWA Kenji National Institute of Animal Health ; Director, 家畜衛生試験場, 部長
和田 久泰 岐阜大学, 医学部, 助手 (10283300)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Atherosclerosis / TNF-α / Apolipoprotein E / Knockout Mice / Macrophage / ICAM-1 / VCAM-1 / MCP-1 / サイトカイン |
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| Research Abstract |
Atherosclerosis is a complex disease that is characterized by cholesterol deposition and monocyte infiltration into the subendothelial space. Proinflammatory cytokines, such as tumor necrosis factor-α(TNF-α), have been shown to be expressed in human atherosclerotic lesions, particularly in association with infiltrating monocytes and macrophages. TNF-α is thought to have important effects on the various cell types that are components of atherosclerotic lesions. Although considerable evidence regarding the functions of TNF-α has been accumulated in in vitro studies, their precise roles in the development of vascular lesions in bivo have not been established.
The present study was conducted to examine the role of endogenous TNF-α in atherosclerosis. We used mice with a targeted disruption of TNF-αgene(TNF-α^<-1->), and crossed TNF-α^<-1-> mice with apoE^<-1-> mice, an animal model for atherosclerosis.
The present study using apoE^<-1-> and apoE^<-1->/TNF-α^<-1-> mice provided the direct evidence that TNF-α promotes atherosclerotic lesion. The expressions of ICAM-1 and MCP-1 were elevated in apoE^<-1-> mice compared with apoE^<-1->/TNF-α^<-1-> mice. The uptake of oxidized LDL was significantly larger in macrophages from apoE^<-1-> mice than those from apoE^<-1->/TNF-α^<-1-> mice and the expression level or SRA was significantly higher in macrophages from apoE^<-1-> mice than those from apoE^<-1->/ TNF-α^<-1-> mice. TNF-α contributes to the generation of atherosclerotic lesion without the change in serum lipid concentration in apoE^<-1-> mice.
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Report
(3 results)
Research Products
(8 results)
