Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability-analysis in hypercholesterolemic rabbits

Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability-analysis in hypercholesterolemic rabbits
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DOI:
10.1016/j.atherosclerosis.2006.11.031
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发表时间:
2007-11-01
期刊:
影响因子:
5.3
通讯作者:
Saji, Hideo
Saji, Hideo
中科院分区:
医学2区
文献类型:
--
作者:
Ishino, Seigo;Mukai, Takahiro;Saji, Hideo

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凝集素样氧化低密度脂蛋白受体-1(LOX-1)是氧化低密度脂蛋白(Ox-LDL)的细胞表面受体,根据细胞培养实验,它与动脉粥样硬化斑块不稳定性相关的血管细胞功能障碍有关。在本研究中,我们研究了LOX-1的表达和斑块不稳定性之间的关系,在高胆固醇血症的兔体内免疫组织化学分析。我们制备了6只12-24月龄的Watanabe遗传性高脂血症(WHHLMI)家兔的胸主动脉30个系列的横截面,其中观察到70个动脉粥样硬化斑块。采用免疫组化染色、TUNEL染色和Azan-Mallory染色检测动脉粥样硬化斑块中LOX-1、基质金属蛋白酶-9(MMP-9)、单核细胞趋化蛋白-1(MCP-1)的表达、凋亡事件、斑块不稳定指数(斑块形态不稳定的指标)和纤维肌帽厚度。LOX-1表达与斑块不稳定指数、MMP-9表达呈正相关。LOX-1表达在纤维肌帽较薄(< 100 μ m)的动脉粥样硬化斑块中更为显著。此外,LOX-1的表达显示在巨噬细胞丰富的脂质核心区,MCP-1的表达和凋亡事件是突出的。这些结果表明,LOX-1的表达增强与高胆固醇血症兔中组织学不稳定的动脉粥样硬化斑块相关,表明LOX-1参与了体内动脉粥样硬化斑块的不稳定。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Lectin-like oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL (Ox-LDL), has been implicated in vascular cell dysfunction related to atherosclerotic plaque instability, according to cell culture experiments. In the present study, we investigated the relationship between LOX-1 expression and plaque instability in hypercholesterolemic rabbits by immunohistological analyses in vivo. We prepared thirty series of cross sections of the thoracic aorta from six myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits (12-24 months), in which seventy atherosclerotic plaques were observed. LOX-1, matrix metal loproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1) expression, apoptotic events, plaque instability index (an index of the morphological destabilization of atherosclerotic plaques) and fibromuscular cap thickness in each atherosclerotic plaque were determined by immunohistochemical staining, TUNEL staining and Azan-Mallory staining. LOX-1 expression was positively correlated with the plaque instability index and MMP-9 expression. LOX-1 expression was more prominent in atherosclerotic plaques with thinner fibromuscular cap (< 100 mu m). Furthermore, LOX-1 expression was shown in the macrophage-rich lipid core area where MCP-1 expression and apoptotic events were prominent. These results indicate that enhanced LOX-1 expression was associated with histologically unstable atherosclerotic plaques in hypercholesterolemic rabbits, suggesting the involvement of LOX-1 in the destabilization of atherosclerotic plaques in vivo. (c) 2006 Elsevier Ireland Ltd. All rights reserved.