In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid
In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid
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DOI：
10.1161/atvbaha.108.171736
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发表时间：
2008-12-01
影响因子：
8.7
通讯作者：
Ogawa, Yoshihiro
中科院分区：
文献类型：
--
作者：
Yamada, Hideto;Yoshida, Masayuki;Ogawa, Yoshihiro
一项大规模、前瞻性、随机临床试验最近显示，在低剂量他汀类药物治疗中加入高纯度二十碳五烯酸（EPA）可显著降低主要冠状动脉事件的发生率。在这里，我们研究了在体内和体外的影响，EPA对单核细胞粘附内皮细胞和adhesionmolecules.Methods和结果-一个新的正面免疫组织化学的内皮表面结合共聚焦显微镜显示显着减少脂多糖（LPS）诱导的单核细胞粘附到主动脉内皮细胞与血管细胞粘附分子1（VCAM-1）的抑制平行。和相对于载体处理组，EPA处理小鼠中核因子-κ B p65的核转位。在生理流动条件下的体外粘附测定系统中，EPA抑制LPS诱导的单核细胞粘附和内皮细胞粘附分子。我们发现代谢综合征患者服用高纯度EPA（每日1.8 g）3个月后，可溶性细胞间粘附分子1（sICAM-1）和sVCAM-1的血浆浓度显著降低。多变量回归分析显示EPA给药是sICAM-1和sVCAM-1的唯一独立决定因素。结论-本研究提供证据表明EPA在体内和体外抑制内皮细胞粘附分子的同时抑制单核细胞与内皮细胞的粘附。（Arterioscler Thromb Vasc Biol.2008;28：2173-2179.）
Objective - A large-scale, prospective, randomized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid (EPA) to low-dose statin therapy significantly reduces the incidence of major coronary events. Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules.Methods and Results - A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 (VCAM-1) and nuclear translocation of nuclear factor-kappa B p65 in EPA-treated mice relative to vehicle-treated groups. In an in vitro adhesion assay system under physiological flow conditions, EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules. We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA (1.8 g daily). Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1.Conclusions - This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro. (Arterioscler Thromb Vasc Biol. 2008;28:2173-2179.)