Alteration of volume-regulated chloride channel during macrophage-derived foam cell formation in atherosclerosis
Alteration of volume-regulated chloride channel during macrophage-derived foam cell formation in atherosclerosis
复制标题
动脉粥样硬化巨噬细胞衍生泡沫细胞形成过程中容量调节氯通道的变化
DOI：
10.1016/j.atherosclerosis.2011.01.035
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发表时间：
2011-05-01
期刊：
影响因子：
5.3
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
--
作者：
Hong, Liang;Xie, Zhi-Zhong;Guan, Yong-Yuan
目的：容积调节性氯离子通道（VRCC）在多种生理功能的调节中起着重要作用。然而，很少有人知道VRCC是否参与动脉粥样硬化。在这项研究中，我们研究了VRCC泡沫细胞形成过程中的功能在macrophage.Methods和结果：处理RAW264.7细胞与ox-LDL增加细胞内胆固醇含量以及细胞体积。ox-LDL处理后，等渗溶液中静息[Cl（-）]（i）降低。低渗溶液使细胞内[Cl（-）]（i）降低，并诱发体积调节性Cl（-）电流，但肿胀引起的[Cl（-）]（i）降低和Cl（-）电流增加在ox-LDL处理的细胞中更为明显。容积调节性Cl（-）运动的增加与细胞内胆固醇含量呈正相关。此外，高脂饮食ApoE（-/-）小鼠腹腔巨噬细胞肿胀诱导的Cl（-）运动和电流较对照组增强，其增量与动脉粥样硬化斑块面积呈正相关。最后，低渗介质激活VRCC显著加速ox-LDL诱导的巨噬细胞源性泡沫细胞形成，而Cl（-）通道阻断剂抑制VRCC则显著减弱ox-LDL诱导的巨噬细胞源性泡沫细胞形成。VRCC的激活加速，而抑制VRCC衰减，ox-LDL诱导的巨噬细胞中的脂质积累，表明VRCC参与泡沫细胞形成的调节。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Volume-regulated Cl(-) channel (VRCC) plays a critical role in regulation of a variety of physiological functions. However, little is known whether VRCC is involved in atherosclerosis. In this study, we investigated the functions of VRCC during foam cell formation in macrophages.Methods and results: Treatment of RAW264.7 cells with ox-LDL increased intracellular cholesterol content as well as cell volume. After ox-LDL treatment, the resting [Cl(-)](i) in isotonic solution was decreased. Hypotonic solution reduced [Cl(-)](i) and evoked volume-regulated Cl(-) current in all the cells, however, the swelling-induced reduction of [Cl(-)](i) and increase of Cl(-) current were more prominent in ox-LDL treated cells than that in control. The increases of volume-regulated Cl(-) movement positively correlated with the intracellular cholesterol content. Moreover, in peritoneal macrophages isolated from high-fat diet ApoE(-/-) mice, the swelling-induced Cl(-) movement and current were enhanced compared with those in control group, and their increments positively correlated with atherosclerotic plaque area. Finally, activation of VRCC by hypotonic medium significantly accelerated, whereas, inhibition of VRCC with Cl(-) channel blockers remarkably attenuated, ox-LDL-induced macrophage-derived foam cell formation.Conclusion: The activity of VRCC is augmented during macrophage-derived foam cell formation. Activation of VRCC accelerated, whereas, inhibition of VRCC attenuated, ox-LDL-induced lipid accumulation in macrophages, suggesting VRCC is involved in the regulation of foam cell formation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.