Lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for remnant-like lipoprotein particles (RLPs) and mediates RLP-induced migration of vascular smooth muscle cells
Lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for remnant-like lipoprotein particles (RLPs) and mediates RLP-induced migration of vascular smooth muscle cells
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DOI：
10.1016/j.atherosclerosis.2007.12.017
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发表时间：
2008-06-01
期刊：
影响因子：
5.3
通讯作者：
Kume, Noriaki
中科院分区：
文献类型：
--
作者：
Aramaki, Yo;Mitsuoka, Hirokazu;Kume, Noriaki
目的：残留样脂蛋白颗粒（RLP）与动脉粥样硬化形成有关，尤其是糖尿病血脂异常；然而，它们的受体以及对血管平滑肌细胞（VSMC）的影响仍不清楚。在本研究中，我们检测了凝集素样氧化LDL受体-1（LOX-1）是否作为RLPs受体及其在VSMC中的生物学效应。方法和结果：通过含有抗载脂蛋白A-I和抗载脂蛋白B-100单克隆抗体的免疫亲和凝胶从人血浆中分离RLPs。 DiI 标记的 RLP 被稳定表达 LOX-1 的 CHO-K1 细胞摄取，但不被野生型 CHO-K1 细胞摄取。 RLP 在牛 VSMC (BVSMC) 中诱导 LOX-1 表达和细胞迁移，而用 LOX-1 特异性 siRNA 转染可显着抑制这种情况。金属蛋白酶抑制剂、表皮生长因子（EGF）受体酪氨酸激酶、肝素结合EGF样生长因子（HB-EGF）、p38丝裂原激活蛋白激酶（p38 MAPK）、MAPK激酶（MEK1）和磷酸肌醇3激酶（PI3K）显着阻断RLP诱导的BVSMCs的LOX-1表达和细胞迁移。结论：本研究提供直接证据表明 LOX-1 是 VSMC 中 RLP 的新型受体。因此，LOX-1 介导的 RLP 摄取可能通过诱导 LOX-1 表达和 VSMC 迁移，在动脉粥样硬化形成中发挥重要作用，特别是在餐后高脂血症、糖尿病和代谢综合征的情况下。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Objective: Remnant-like lipoprotein particles (RLPs) have been implicated in atherogenesis especially by diabetic dyslipidemia; however, their receptor(s) and effects on vascular smooth muscle cells (VSMCs) remain unclear. In this study, we examined if lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for RLPs and its biological effects in VSMCs.Methods and results: RLPs were isolated from human plasma by immunoaffinity gel containing anti-apolipoprotein A-I and anti-apolipoprotein B-100 monoclonal antibodies. DiI-labeled RLPs were taken up by CHO-K1 cells stably expressing LOX-1 but not by wild-type CHO-K1 cells. RLPs induced LOX-1 expression and cell migration in bovine VSMCs (BVSMCs), which were significantly suppressed by transfection with LOX-1 specific siRNAs. Inhibitors of metalloproteinases, epidermal growth factor (EGF) receptor tyrosine kinase, heparin-binding EGF-like growth factor (HB-EGF), p38 mitogen-activated protein kinase (p38 MAPK), MAPK kinase (MEK1) and phosphoinositide 3-kinase (PI3K) significantly blocked RLP-induced LOX-1 expression and cell migration of BVSMCs.Conclusions: The present study provides direct evidence that LOX-1 is a novel receptor for RLPs in VSMCs. LOX-1-mediated uptake of RLPs may thus play important roles in atherogenesis by inducing LOX-1 expression and VSMC migration especially in the settings of postprandial hyperlipidemia, diabetes and metabolic syndrome. (C) 2008 Elsevier Ireland Ltd. All rights reserved.