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The mechanisms of atheroma formation in vessel wall using a unique monoclonal antibody(ASH1a/256C) recognizing. atherosclerotic lesions.

使用独特的单克隆抗体（ASH1a/256C）识别血管壁粥样斑块形成的机制。

基本信息

批准号：
14572068
负责人：
MORI Masahiro
金额：
$ 1.92万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

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 dropletsThe expression of PC-cholesterol complex correlates foam cell rupture and accumulation of lipid in extracellular space in intima

为了研究其在心血管疾病低侵袭性诊断中的应用，制备了在体内和体外识别动脉粥样硬化脂肪条纹的新型单克隆抗体（ASH 1a/256 C）。WHHL兔ASH 1a/256 C抗原的纯化（一种家族性高脂血症的模型动物PC-胆固醇复合物的表达与内膜中泡沫细胞破裂和细胞外间隙中脂质积聚相关）动脉粥样硬化被确定为“PC-胆固醇复合物”，其特异性地定位于增厚内膜中的细胞外间隙中。只有当巨噬细胞与乙酰化LDL、WHHL兔血清或人高脂血症血清孵育时，才能观察到“（游离胆固醇）富集的脂滴”。VLDL/IDL也能诱导泡沫细胞形成，但未观察到富含FC的脂滴。含富FC脂滴的泡沫细胞连续培养至2周;当巨噬细胞与胆固醇油酸酯液晶共同孵育时，（不含PC），巨噬细胞也能产生PC-胆固醇复合物由于U18666 A抑制细胞胆固醇转运，当泡沫细胞与这种材料连续孵育时，泡沫细胞不能自行破裂。这些观察结果表明，CE（胆固醇酯）的水解和细胞内胆固醇的转运是富FC脂滴形成的重要过程，PC-胆固醇复合物的表达与内膜泡沫细胞破裂和细胞外间隙脂质积聚有关。