title: Alteration of volume-regulated chloride channel during macrophage-derived foam cell formation in atherosclerosis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Cardiac and Cerebrovascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan 2 Rd, Guangzhou 510080, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hong
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Xie
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Du
authors.forename: Yong-Bo
authors.initials: YB
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Lv
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D048429:Cell Size; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats; D004195:Disease Models, Animal; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007038:Hypotonic Solutions; D015640:Ion Channel Gating / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009579:Nitrobenzoates / Q000494:pharmacology; D009994:Osmolar Concentration; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D000873:Anthracenes; D001057:Apolipoproteins E; D018118:Chloride Channels; D002712:Chlorides; D004041:Dietary Fats; D007038:Hypotonic Solutions; D008077:Lipoproteins, LDL; D009579:Nitrobenzoates; C099252:oxidized low density lipoprotein; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C010030:9-anthroic acid; D002784:Cholesterol