Cholesteryl esters of aggregated LDL are internalized by selective uptake in human vascular smooth muscle cells
Cholesteryl esters of aggregated LDL are internalized by selective uptake in human vascular smooth muscle cells
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DOI：
10.1161/01.atv.0000193618.32611.8b
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发表时间：
2006-01-01
影响因子：
8.7
通讯作者：
Badimon, L
中科院分区：
文献类型：
--
作者：
Llorente-Cortés, V;Otero-Viñas, M;Badimon, L
目的：低密度脂蛋白受体相关蛋白(LRP1)介导聚集的低密度脂蛋白(AgLDL)内化到人血管平滑肌细胞(VSMC)中。LRP1介导的agLDL摄取诱导细胞内高胆固醇酯(CE)积聚。本研究的目的是研究agLDL在人血管内皮细胞中的内化机制。方法和结果：用[H-3]标记低密度脂蛋白的脂类成分，用[I-125]标记载脂蛋白成分。我们发现，来自agLDL摄取的细胞内CE的90%与apoB100的降解无关，但选择性地从agLDL中摄取。小干扰RNA抑制LRP1的表达导致agLDL-CE选择性摄取减少80+/-0.05%。AgLDL可诱导CE在细胞内蓄积，而不伴随CE的合成。胞浆和细胞骨架蛋白不是CE转运所必需的。电子显微镜和共聚焦显微镜实验表明，来源于agLDL的CE在脂联素染色的脂滴中积聚，高密度脂蛋白不能去除这些脂滴。结论LRP1介导了从agLDL选择性摄取CE，来源于agLDL的CE不是在细胞内加工，而是储存在脂滴中。
Objective - Low-density lipoprotein (LDL) receptor-related protein (LRP1) mediates the internalization of aggregated LDL (agLDL)-LDL trapped in the arterial intima bound to proteoglycans-into human vascular smooth muscle cells (VSMC). LRP1-mediated agLDL uptake induces high-intracellular cholesteryl ester (CE) accumulation. The aim of this study was to characterize the mechanism of agLDL internalization in human VSMC.Methods and Results - The lipidic component of LDL was labeled with [H-3] and the apolipoprotein component with [I-125]. We found that > 90% of intracellular CE derived from agLDL uptake was not associated with apoB100 degradation but was selectively taken up from agLDL. The inhibition of LRP1 expression by small interfering RNA treatment led to a decrease of 80 +/- 0.05% in agLDL-CE selective uptake. AgLDL induced intracellular CE accumulation without a concomitant CE synthesis. Cytosolic and cytoskeletal proteins were not required for CE transport. Electron and confocal microscopy experiments indicate that CE derived from agLDL accumulated in adipophilin-stained lipid droplets that were not removable by high-density lipoprotein.Conclusions - Taken together, these results demonstrate that LRP1 mediates the selective uptake of CE from agLDL and that CE derived from agLDL is not intracellularly processed but stored in lipid droplets in human VSMC.