DEVELOPMENT OF NEW THERAPY FOR ATHEROSCLEROSIS TARGETING NATURAL KILLER T (NKT) CELLS
| Project/Area Number |
14370215
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
FUJII Satoshi Hokkaido University Hospital, Lecturer, 病院, 講師 (90291228)
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| Co-Investigator(Kenkyū-buntansha) |
ONOE Kazunori Institute for Genetic Medicine, Professor, 遺伝子病制御研究所, 教授 (40002117)
IWABUCHI Kazuya Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (20184898)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | atherosclerosis / bone marrow derived cells / lymphocyte / NKT cells / mouse / CD1d molecule / gene / cytokine |
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| Research Abstract |
The potential role of CD1d-restricted natural killer T (NKT) cells in the development of atherosclerosis was investigated. When fed an atherogenic diet (AD), NKT cell-deficient CD1d^<-/-> mice had significantly smaller atherosclerotic lesions than AD-fed C57BL/6 (WT) mice. As compared with chow-fed WT mice, administration of the NKT cell ligand α-galactosylceramide (α-GalCer) to AD-fed WT mice resulted in a T helper 1 (Th1)-shifted cytokine response. In addition, repeated injection of α-GalCer or the related glycolipid OCH to apolipoprotein E knockout (apoE^<-7->) mice during the early phase of atherosclerosis significantly enlarged the lesion areas compared to mice injected with vehicle control. However, administration of α-GalCer to apoE^<-/-> mice at the late phase of the disease process (with already established atherosclerotic lesions) exerted no significant influence on the lesion area, but considerably decreased the collagen content. Development of atherosclerosis in either AD-fed WT or apoE^<-/-> mice was associated with the presence of Vα14Jα18 transcripts in the atherosclerotic arterial walls, indicating that NKT cells were recruited to these lesions. Thioglycolate-elicited macrophages pursed with oxidized low-density lipoproteins expressed enhanced CD1d levels and induced NKT cells to produce interferon-γ, a potentially pro-atherogenic Th1 cytokine. Collectively, we conclude that NKT cells are pro-atherogenic in mice.
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Sensitive detection of myocardial viability in chronic coronary artery disease by ultrasonic integrated back scatter analysis.2005
Author(s)
Komuro K, Yamada S, Mikami T, Yoshinaga K, Noriyasu K, Goto K, Onozuka H, Urasawa K, Fujii S, Tamaki N, Kitabatake A.
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Journal Title
J Am Soc Echocardiogr 18
Pages: 26-31
Description
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[Journal Article] Loss of IRS-1 signaling induces the cardiovascular and proteo(fibrino)lytic system derangements typical of insulin resistance.2005
Author(s)
Furumoto T, Fujii S, Onozuka H, Zaman T, Goto D, Sugawara T, Mikami T, Watanabe S, Abe K, Terauchi Y, Kadowaki T, Kitabatake A, Sober BE.
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Journal Title
Coronary Art Disease 16
Pages: 117-123
Description
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[Journal Article] Interleukin-6 and mevastatin regulate plasminogen activator inhibitor-1 through CCAAT/enhancer-binding proteinδ2005
Author(s)
Dong J, Fujii S, Li H, Nakabayashi H, Sakai M, Nishi S, Goto D, Furumoto T, Imagawa S, Zaman T, Kitabatake A.
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Journal Title
Arterioscler Thromb vase Biol 25
Pages: 1078-1084
Description
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[Journal Article] Natural killer T cells accelerate atherogenesis in mice.2004
Author(s)
Nakai Y, Iwabuchi K, Fujii S, Ishimori N, Dashtsoodol N, Watano K, Mishima T, Iwabuchi C, Tanaka S, Bezbradica J, Nakayama T, Taniguchi M, Miyake S, Yamamura T, Kitabatake A, Joyce S, Van Kaer L, Onoe K.
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Journal Title
Blood 104
Pages: 2051-2059
NAID
Description
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[Journal Article] Coronary capillary network remodeling and hypofibrinolysis in aged obese diabetic rats : Implications for increased myocardial vulnerability to ischemia.2003
Author(s)
Sugawara T, Fujii S, Zaman AKM T, Goto D, Furumoto T, Imagawa S, Dong J, Sakuma I, Jesmin S, Togashi H, Yoshioka M, Koyama T, Kitabatake A.
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Journal Title
Mol Cell Biochem 248
Pages: 165-170
Description
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[Journal Article] Intracellular signal transduction modulating expression of plasminogen activator inhibitor-1 in adipocytes.2003
Author(s)
Goto D, Fujii S, Kaneko T, Furumoto T, Sugawara T, Zaman AKM T, Imagawa S, Dong J, Nakai Y, Mishima T, Sobel BE, Kitabatake A.
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Journal Title
Biochem Pharmacol 65
Pages: 1907-1914
Description
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[Journal Article] Measuring medium-sized muscular arteries using a novel broadband 15-MHz linear array probe.2003
Author(s)
Yamada S, Mikami T, Nishihara K, Mitake T, Izumi M, Yoshida N, Hanaoka A, Wu D, Komuro K, Onozuka H, Fujii S, Kitabatake A.
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Journal Title
J Med Ultrasonics 30
Pages: 177-185
NAID
Description
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[Journal Article] In vivo echocardiographic detection of cardiovascular lesions in apolipoprotein E-knockout mice using a novel high-frequency high-speed echocardiography.2002
Author(s)
Onozuka H, Fujii S, Mikami T, Yamada S, Ishimori N, Shimizu T, Furumoto T, Nakai Y, Komuro K, Nishihara K, Okamoto H, Kitabatake A.
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Description
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