Inhibitory Effect of Delphinidin on Monocyte-Endothelial Cell Adhesion Induced by Oxidized Low-Density Lipoprotein via ROS/p38MAPK/NF-κB Pathway
Inhibitory Effect of Delphinidin on Monocyte-Endothelial Cell Adhesion Induced by Oxidized Low-Density Lipoprotein via ROS/p38MAPK/NF-κB Pathway
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DOI：
10.1007/s12013-011-9216-2
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发表时间：
2011-11-01
影响因子：
2.6
通讯作者：
Yu, Bin
中科院分区：
文献类型：
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作者：
Chen, Chun-ye;Yi, Long;Yu, Bin
单核细胞粘附到血管内皮及其随后的跨内皮迁移是动脉粥样硬化形成的关键早期事件。在本研究中，研究了花青素类飞燕草素对 ox-LDL 诱导的单核细胞与内皮细胞粘附的影响。结果表明，飞燕草素（50、100或200μM）预处理可剂量依赖性地降低ox-LDL诱导的ICAM-1和P-选择素表达上调，以及单核细胞粘附和迁移的增强。为了确定 ROS/p38MAPK/NF-kappa B 通路的作用，测量了细胞内 ROS 水平、p38MAPK 蛋白表达、NF-kappa B 转录活性和蛋白表达、I kappa B-α 降解、NADPH 氧化酶亚基（Nox2 和 p22phox）蛋白和 mRNA 表达。结果表明，花翠素以剂量依赖性方式减弱ox-LDL诱导的内皮细胞中ROS的产生、p38MAPK蛋白表达、NF-kappa B转录活性和蛋白表达、I kappa B-α降解、NADPH氧化酶亚基（Nox2和p22phox）蛋白和mRNA表达。这些结果表明，飞燕草素通过抑制 ROS/p38MAPK/NF-kappa B 途径，减弱 ox-LDL 诱导的粘附分子（P-选择素和 ICAM-1）表达以及单核细胞与内皮细胞的粘附。这些发现为设计有效的抗动脉粥样硬化药物奠定了基础，这些药物在预防 AS 方面具有治疗潜力。
Monocyte adhesion to the vascular endothelium and their subsequent trans-endothelial migration are pivotal early events in atherogenesis. In this study, the effect of delphinidin, belonging to the group of anthocyanin, on adhesion of monocytes to endothelial cells induced by ox-LDL was investigated. The results showed that the pre-treatment with delphinidin (50, 100, or 200 mu M) dose-dependently decreased the ox-LDL-induced up-regulation of the expression of ICAM-1 and P-selectin, and the enhanced adhesion and transmigration of monocytes. To determine the role of ROS/p38MAPK/NF-kappa B pathway, intracellular ROS level, p38MAPK protein expression, NF-kappa B transcription activity and protein expression, I kappa B-alpha degradation, NADPH oxidase subunit (Nox2 and p22phox) protein, and mRNA expression were measured. The results showed that delphinidin attenuated ox-LDL-induced generation of ROS, p38MAPK protein expression, NF-kappa B transcription activity and protein expression, I kappa B-alpha degradation, NADPH oxidase subunit (Nox2 and p22phox) protein and mRNA expression in endothelial cells in a dose-dependent manner. These results suggest that delphinidin attenuates ox-LDL induced expression of adhesion molecules (P-selectin and ICAM-1) and the adhesion of monocytes to endothelial cells by inhibiting ROS/p38MAPK/NF-kappa B pathway. These findings provide a basis for the design of potent antiatherosclerotic agents that will have therapeutic potential in the prevention of AS.