| Project/Area Number |
07557074
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Osaka Unviresity |
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Principal Investigator |
NOZAKI Shuichi Osaka University, Medical School, Assistant Professor, 医学部, 助手 (30252646)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIWAGI Hirokazu Osaka University, Hospital, Medical Staff, 医学部・附属病院, 医員
KURATA Yoshiyuki Osaka University, Medical School, Lecturer, 医学部, 講師 (80127224)
YAMASHITA Shizuya Osaka University, Medical School, Assistant Professor, 医学部, 助手 (60243242)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 1996: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | CD36 / oxidized LDL / atherosclerosis / モデル動物 |
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| Research Abstract |
CD36 is a glycoprotein with a molecular weight of 88 kDa and is expressed on platelets, monocytes/macrophages and capillary endothelial cells and adipocyte. We and others demonstrated that CD36 deficiency can be divided into two subgroups. In type I deficiency, neither platelets nor monocytes express CD36 ; in type II deficiency, monocytes express CD36 but platelets do not. We previously clarified three types of gene abnormalities (substitution of Pro90 by Ser, deletion of dinucleotide in exon V,and insertion of single nucleotide in exon X) in CD36-deficient subjects. All these abnormalities result in the absence of CD36 expression on the cell surface. CD36 has been proposed to be a multifunctional molecule such as a thrombospondin, collagen on platelets and oxidized LDL on macrophages. We previously reported that uptake of oxidized LDL by CD36 deficient macrophages was reduced compared with that by control macrophages and reported that CD36 was a physiologically important receptor for oxidized LDL to form foam cells in atherosclerotic lesions. In the present study, we investigated the expression of CD36 in human aorta and found that CD36 was highly expressed on lipid-laden macrophages. The distribution of CD36 expression was different from that of scavenger type I and type II.CD36 was highly positive in the core of atherosclerotic lesions. We also found that oxidized LDL increased the expression of CD36 on macrophages. Based on these findings, we tried to establish transgenic mouse in order to further clarify the role of CD36 on atherosclerosis. We made a construct for CD36 transgenic mouse including chickenbeta actin promoter and injected the construct to eggs and obtained 50 mice. We found that 8 mice was positive for human CD36 gene and that mRNA was expressed in heart and liver tissues. We analyzed the immunohistochemical expression of CD36 on macrophages obtained from the blood of each mouse. No mice presented overexpression of CD36 on macrophages.
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