| Project/Area Number |
10670210
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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 |
Experimental pathology
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| Research Institution | Saga Medical School |
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Principal Investigator |
TOKUNAGA Osamu Saga Medical School, Pathology Department, Professor, 医学部, 教授 (40113229)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Toshimi Saga Medical School, Pathology Department, Associate Professor, 医学部, 助教授 (20162456)
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| Project Period (FY) |
1998 – 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: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | human / atherosclerosis / endothelium / variant / gene / mutation / FISH / 内皮細胞 / バリアント / LDL / caveolin / バリアント内皮 / 遺伝子異常 |
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| Research Abstract |
Existence of large endothelial cells in the human aorta, especially on atherosclerotic lesions has been reported. They have multiple nuclei and are called "multinucleated variant endothelial cells (MVECs)". MVECs express p53 tumor suppressor gene and have chromosomal aneuploidy. During the present study period, it was found that MVECs over -expressed LDL receptor and have enhanced uptake of native LDL.
In the latest study, caveolin expression was demonstrated in MVECs, but the density of it is similar to typical small mononuclear endothelial cells (TECs). However, the size of caveoles was greater in MVECs than TECs. This may reflect the overexpression of LDL receptor on the cell surface. In fact, LDL-gold uptake study demonstrated 4.5-fold greater amount of gold particles per cell surface unit area in the MVECs. The LDL-gold particles were located in plasmalemmal vesicles, and in endosomes or lysosomes of MVECs with occasional opening on the abluminal surface, whereas few particles were found in TECs. These findings indicate that MVECs have a greater capacity to transport LDL cholesterol than that of TECs.
LDL oxidation was demonstrated in the cytoplasm of ECs, , especially of MVECs when cultured in the presence of ferritin. The intracellular oxidative modification of LDL (IOM-LDL) was blocked by iron chelator or antioxidants. These observations suggest that ECs have IOM-LDL which was catalyzed by iron released from ferritin. MVECs contribute to the development and advancement of atherosclerotic lesions.
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