| Project/Area Number |
10671070
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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 | Osaka University |
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Principal Investigator |
YAMASHITA Shizuya Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (60243242)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Makoto Osaka University Graduate School of Medicine, Assistant Prof., 医学部・附属病院, 医員
TOMIYAMA Yoshiaki Osaka University Graduate School of Medicine, Assistant Prof., 医学系研究科, 助手 (80252667)
野崎 秀一 大阪大学, 医学部, 助手 (30252646)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Idiopathic Cardiomyopathy / CD36 Deficiency / Myocardial Energy Metabolism / Long-chain Fatty Acid Transporter / Knockout mice / Cardiac Hypertrophy / 特発生心筋症 / CD36 / 長鎖脂肪酸 / エネルギー代謝 |
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| Research Abstract |
CD36 is an 88 kDa membrane glycoprotein and is expressed on platelets, monocytes, monocyte-derived macrophages and adipose tissues. CD36 was reported to be a receptor for collagen and thrombospondin as well as a transporter of long-chain fatty acids. We have identified patients with CD36 deficiency and reported 3 novel mutations in the CD36 gene. We also found that CD36 is a receptor for oxidized LDL, using monocyte-derived macrophages from CD36-deficient subjects and that CD36 is expressed on foamed macrophages in the human atherosclerotic aorta and coronary arterise. We also found that CD36 is expressed on the cardiac myocytes. CD36-deficient subjects lack CD36 on the cardiomyocytes and some of them develop idiopathic cardiomyopathy. So far, we identified 26 CD36-deficient subjects, all of whom showed a complete deficiency of myocardial uptake of ィイD1123ィエD1I-BMIPP, a long-chain fatty acid analogue. Six subjects were accompanied by hypertrophic or dilated cardiomyopathy. FDG-PET anlysis demonstrated that glucose uptake by the heart muscle was rather accelerated in the CD36-deficient subjects compared with conmtrol subjects. Thus, the impaired mayocardial uptake of long-chain fatty acids may lead to an energy switching from long-chain fatty acids to glucose in CD36 deficiency. To further examine the possible contribution of CD36 deficiency to the pathogenesis of cardiomyopathy, we are trying to establish CD36 knockout mice by genetic engineering technique. We are planning to evaluate the presence or absence of impaired cardiac function, cardiac hypertrophy or dilated cardiomyopathy in this animal model to establish the significance of CD36 deficiency in the pathogenesis of cardiomyopathy.
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