2003 Fiscal Year Final Research Report Summary
The mechanisms of atheroma formation in vessel wall using a unique monoclonal antibody(ASH1a/256C) recognizing. atherosclerotic lesions.
| Project/Area Number |
14572068
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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 |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
MORI Masahiro Teikyo University, Fac. Pharm. Sci, Research Assoc., 薬学部, 助手 (00230079)
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| Project Period (FY) |
2002 – 2003
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| Keywords | atherosclerosis / foam cell / cholesterol / apoptosis / lipid droplets / modified LDL / monoclonal antibody / non-invasive diagnosis |
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| Research Abstract |
In order to investigate application for low invasive diagnosis of cardiovascular disease, novel monoclonal antibodies (ASH1a/256C) recognizing fatty streaks of atheroma in vivo and in vitro were prepared. The ASH1a/256C antigen purified from WHHL rabbit (a model animal for familial hyper The expression of PC-cholesterol complex correlates foam cell rupture and accumulation of lipid in extracellular space in intima) atheroma was determined as "PC-cholesterol complex" specifically localized in extracellular space in thickened intima.
Foam cells can produce this antigen as "FC (free cholesterol) enriched lipid droplets", only when macrophages incubated with Acetylated LDL, WHHL rabbit serum or Human hyperlipidemic serum. VLDL/IDL could also induce foam cell formation, however, no FC-rich lipid droplets were observed. The foam cells containing FC-rich lipid droplets were cultured continuously until 2 weeks ; finally, the foam cells ruptured and lipid droplets remained in extracellular matrix.
When the macrophage incubated with cholesterol oleate liquid crystals (not contain PC), macrophages could also produce PC-cholesterol complex (FC-rich lipid droplets) and change to foam cells morphologically, Since U18666A inhibited cellular cholesterol transport, when the foam cell incubated continuously with this material, foam cells failed to rupture themselves. These observation suggest that hydrolysis of CE (cholesteryl ester) and cellular cholesterol transport are important process for the formation of FC-rich lipid droplets
The expression of PC-cholesterol complex correlates foam cell rupture and accumulation of lipid in extracellular space in intima
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[Publications] Fujimoto, Y., Itabe, H., Mori, M., Higashi, Y., Kojima, S., Takano, T.: "Identification of the major lipid droplet proteins of the human hepatocyte cell line HuH7"Biochemica.Biophysica.Acta. 1644. 47-59 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Fujumoto, Y., Itabe, H., Mori, M., Higashi, Y., Kojima, S.Takano, T.: "Identification of the major lipid, droplet proteins of the human hepatocyte cell line HmH7"Biochemica. Biophysica. Acta. 1644. 47-59 (2003)
Description
「研究成果報告書概要(欧文)」より
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