کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5949690 | 1172390 | 2011 | 8 صفحه PDF | دانلود رایگان |

ObjectiveVolume-regulated Clâ 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 resultsTreatment of RAW264.7 cells with ox-LDL increased intracellular cholesterol content as well as cell volume. After ox-LDL treatment, the resting [Clâ]i in isotonic solution was decreased. Hypotonic solution reduced [Clâ]i and evoked volume-regulated Clâ current in all the cells, however, the swelling-induced reduction of [Clâ]i and increase of Clâ current were more prominent in ox-LDL treated cells than that in control. The increases of volume-regulated Clâ movement positively correlated with the intracellular cholesterol content. Moreover, in peritoneal macrophages isolated from high-fat diet ApoEâ/â mice, the swelling-induced Clâ 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 Clâ channel blockers remarkably attenuated, ox-LDL-induced macrophage-derived foam cell formation.ConclusionThe 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.
Journal: Atherosclerosis - Volume 216, Issue 1, May 2011, Pages 59-66