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Altered gene expression of endothelial cell and atherosclerosis.

改变内皮细胞和动脉粥样硬化的基因表达。

基本信息

批准号：
10670210
负责人：
TOKUNAGA Osamu
金额：
$ 1.92万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670210/
关键词：
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

项目摘要

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.

在人类主动脉中，特别是在动脉粥样硬化病变中存在大的内皮细胞已经被报道。它们具有多个细胞核，被称为“多核变异内皮细胞（MVEC）”。MVEC表达p53肿瘤抑制基因，具有染色体非整倍性。在本研究期间，发现MVECs过度表达LDL受体，并增强天然LDL的摄取。在最新的研究中，在MVECs中证实了小窝蛋白的表达，但其密度与典型的小单核内皮细胞（TEC）相似。然而，微血管内皮细胞的小窝的大小大于TEC。这可能反映了细胞表面LDL受体的过度表达。事实上，LDL-金摄取研究表明MVEC中每细胞表面积的金颗粒量是其4.5倍。LDL-金颗粒位于质膜囊泡、内体或溶酶体中，偶尔在腔外表面上有开口，而在TEC中发现很少颗粒。这些结果表明，MVEC比TEC具有更强的转运LDL胆固醇的能力，并且在铁蛋白存在下培养的MVEC的细胞质中证实了LDL氧化，特别是MVEC。LDL的细胞内氧化修饰（IOM-LDL）被铁螯合剂或抗氧化剂阻断。这些观察结果表明EC具有IOM-LDL，其由铁蛋白释放的铁催化。MVEC有助于动脉粥样硬化病变的发展和进展。