Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells
Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells
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DOI：
10.1006/jmcc.1999.1041
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发表时间：
1999-12-01
影响因子：
5
通讯作者：
Sawamura, T
中科院分区：
文献类型：
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作者：
Aoyama, T;Fujiwara, H;Sawamura, T
氧化低密度脂蛋白(OxLDL)及其脂质成分溶血磷脂酰胆碱(LPC)引起的内皮功能改变与动脉粥样硬化的形成有关。最近，我们从牛主动脉内皮细胞克隆了凝集素样氧化低密度脂蛋白受体(LOX-1)。它是BAE表面氧化型低密度脂蛋白的主要结合蛋白，在人颈动脉粥样硬化性内膜和正常牛主动脉内膜中均有表达。在本研究中，我们发现OxLDL诱导BAE中LOX-1的表达。OxLDL以剂量和时间依赖的方式上调LOX-1的mRNA和蛋白水平。这种诱导作用被抗LOX-1抗体阻断，OxLDL也增加了袋装OxLDL的摄取活性。同样，OxLDL的主要成分溶血磷脂酰胆碱(LPC)诱导LOX-1在mRNA、蛋白质和活性水平上的表达，表明OxLDL至少部分地通过LPC介导LOX-1的表达。由于LPC没有显著改变LOX-1mRNA的半衰期，这种上调似乎发生在转录水平。这些结果表明，在体内动脉粥样硬化组织中通过LOX-1摄取OxLDL上调了LOX-1的表达，从而进一步促进了摄取和内皮的激活和功能障碍。
A functional change in the endothelium induced by oxidized low density lipoprotein (OxLDL) and its lipid-constituent, lysophosphatidylcholine (LPC), has been implicated in atherogenesis. Recently, we have cloned lectin-like OxLDL receptor (LOX-1) from bovine aortic endothelial cells (BAE). It is the major binding protein for OxLDL on the surface of BAE and is expressed in atheromatous intima of the human carotid artery as well as in intima of normal bovine aorta. In the present study, we found that OxLDL induced the expression of LOX-1 in BAE. OxLDL upregulated the level of mRNA and protein for LOX-1 in a dose- and time-dependent manner. This induction was blocked by anti-LOX-1 antibody, OxLDL also increased the activity for taking up OxLDL in BAG. Similarly, a major constituent of OxLDL, lysophosphatidylcholine (LPC), induced expression of LOX-1 in mRNA, protein and activity level, suggesting the OxLDL induced expression of LOX-1, at least in part, mediated by LPC. Since LPC did not significantly change the half-life of LOX-1 mRNA, the upregulation seemed to occur at the transcriptional level. These results suggest that LOX-1 is upregulated by the uptake of OxLDL through LOX-1 in atheromatous tissues in vivo, which would further enhance the uptake and endothelial activation and dysfunction.