Oxidized low-density lipoprotein contributes to atherogenesis via co-activation of macrophages and mast cells.
Oxidized low-density lipoprotein contributes to atherogenesis via co-activation of macrophages and mast cells.
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DOI：
10.1371/journal.pone.0123088
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Khismatullin DB
中科院分区：
文献类型：
--
作者：
Chen C;Khismatullin DB
氧化低密度脂蛋白（OxLDL）是动脉粥样硬化的危险因素，由于其在内皮功能障碍和泡沫细胞形成中的作用。巨噬细胞和肥大细胞等组织驻留细胞在激活后释放炎症介质，从而导致内皮激活和单核细胞粘附。其中两种介质是由巨噬细胞产生的肿瘤坏死因子（TNF）-α和由肥大细胞产生的组胺。进行静态和微流控流动实验以确定由oxLDL处理的巨噬细胞和肥大细胞的上清液或直接由oxLDL激活的血管内皮上粘附的单核细胞的数量。采用流式细胞术和酶联免疫吸附法分别检测活化内皮细胞表面粘附分子的表达及培养上清中TNF-α和组胺的含量。低剂量oxLDL（8 μg/ml），低于冠状动脉疾病临床表现的阈值，足以激活巨噬细胞和肥大细胞，并通过释放TNF-α和组胺协同增加单核细胞-内皮细胞粘附。内皮细胞直接暴露于更高剂量的oxLDL（80 μg/ml）对单核细胞粘附的影响小于通过oxLDL处理的巨噬细胞和肥大细胞的间接激活。本工作的结果表明，巨噬细胞和肥大细胞的共同激活oxLDL是内皮功能障碍和动脉粥样硬化的重要机制。所观察到的协同效应表明，巨噬细胞和肥大细胞在动脉粥样硬化的早期阶段发挥重要作用。高脂饮食的过敏患者由于动脉血管壁中低密度脂蛋白和组胺的高浓度，可能处于心血管事件的高风险中。
Oxidized low-density lipoprotein (OxLDL) is a risk factor for atherosclerosis, due to its role in endothelial dysfunction and foam cell formation. Tissue-resident cells such as macrophages and mast cells release inflammatory mediators upon activation that in turn cause endothelial activation and monocyte adhesion. Two of these mediators are tumor necrosis factor (TNF)-α, produced by macrophages, and histamine, produced by mast cells. Static and microfluidic flow experiments were conducted to determine the number of adherent monocytes on vascular endothelium activated by supernatants of oxLDL-treated macrophages and mast cells or directly by oxLDL. The expression of adhesion molecules on activated endothelial cells and the concentration of TNF-α and histamine in the supernatants were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. A low dose of oxLDL (8 μg/ml), below the threshold for the clinical presentation of coronary artery disease, was sufficient to activate both macrophages and mast cells and synergistically increase monocyte-endothelium adhesion via released TNF-α and histamine. The direct exposure of endothelial cells to a much higher dose of oxLDL (80 μg/ml) had less effect on monocyte adhesion than the indirect activation via oxLDL-treated macrophages and mast cells. The results of this work indicate that the co-activation of macrophages and mast cells by oxLDL is an important mechanism for the endothelial dysfunction and atherogenesis. The observed synergistic effect suggests that both macrophages and mast cells play a significant role in early stages of atherosclerosis. Allergic patients with a lipid-rich diet may be at high risk for cardiovascular events due to high concentration of low-density lipoprotein and histamine in arterial vessel walls.
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影响因子：
8.3
作者：
HALLER, H;SCHAPER, D;LUFT, FC
通讯作者：
LUFT, FC
影响因子：
4.1
作者：
GEBUHRER, V;MURPHY, JF;MCGREGOR, JL
通讯作者：
MCGREGOR, JL
影响因子：
14.2
作者：
Akdis, CA;Blaser, K
通讯作者：
Blaser, K
DOI：
10.1161/01.atv.14.6.966
发表时间：
1994-06-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
KAARTINEN, M;PENTTILA, A;KOVANEN, PT
通讯作者：
KOVANEN, PT
影响因子：
5.3
作者：
Kaartinen, M;Penttila, A;Kaartinen, M
通讯作者：
Kaartinen, M