title: [Inhibitory effect of blocking MaxiK channel on human monocyte-derived macrophages differentiation into foam cells].
abstract: OBJECTIVE
  To investigate the expression of high-conductance Ca2+-activated potassium channel (MaxiK channel) mRNA and protein during human monocyte-derived macrophage differentiation into foam cells and to study its function in foam cell formation.
  
  
  METHODS
  Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherent method. The obtained monocytes were cultured for 5 days to differentiate into macrophages. Based on establishment of human macrophage-derived foam cells model, the expression of MaxiK channel alpha-subunit was investigated by immunocytochemical staining, RT-PCR and Western blot. Furthermore, the effect of Paxilline, a MaxiK channel-specific inhibitor, on cholesterol metabolism in macrophages incepting oxidized low density lipoprotein (OxLDL) was studied.
  
  
  RESULTS
  After the macrophages were co-incubated with 30 mg/L OxLDL at 37 degrees C for 60 hours, the cellular volume obviously enlarged and many red lipid granules were deposited in cytoplasm. The total amount of cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) in cells markedly increased and the ratio of CE/TC rose from (14.437+/-6.781)% to (57.946+/-3.507)% (n=7, P<0.05). However, the expression of MaxiK channel alpha-subunit had no significant change (P<0.05). Paxilline (5 micromol/L and 10 micromol/L) markedly reduced the content of TC, FC and CE in macrophages and the ratio of CE/TC decreased to (41.217+/-5.584)% (5 micromol/L Paxilline) and (18.017+/-11.559)% (10 micromol/L Paxilline), respectively (n=7, P<0.05). Meanwhile, the red lipid granules deposited in the cytoplasm of macrophages also decreased.
  
  
  CONCLUSIONS
  Blocking MaxiK channel can inhibit human monocyte-derived macrophage to be differentiated into foam cells.
authors.affiliation: Department of Cardiology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Cardiovascular Ion Channelopathy Laboratory, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xin-jun
authors.initials: XJ
authors.lastname: Lei
authors.forename: Ai-qun
authors.initials: AQ
authors.lastname: Ma
authors.forename: Yu-tao
authors.initials: YT
authors.lastname: Xi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Du
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005487:Foam Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D041681:NIH 3T3 Cells
chemical_list: D007211:Indoles; D051664:Kv1.3 Potassium Channel; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; C048220:paxilline