[Inhibition of human macrophage-derived foam cell differentiation by blocking Kv1.3 and Kir2.1 channels].
OBJECTIVE
To investigate the expression of Kv1.3 and Kir2.1 during human monocyte-derived macrophages differentiation into foam cells and their function in foam cells formation.


METHODS
The human macrophage-derived foam cells were obtained by incubating macrophages with ox-LDL (30 mg/L) for 60 h. The expression of Kv1.3 and Kir2.1 channels were examined by immunocytochemistry, RT-PCR and Western blot. Effects of channel blockers (rMargatoxin and BaCl2) on the cellular cholesterol metabolism were studied by measuring the cellular contents of total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) in the presence or absence of the channel blockers.


RESULTS
After incubating macrophages with 30 mg/L ox-LDL for 60 h, the cellular contents of TC, FC and CE were markedly increased and the ratio of CE/TC was raised from (14.4+/-6.8)% to (57.9+/-3.5)% (P<0.05), which indicated that the cells had differentiated into foam cells. The expression of Kv1.3 and Kir2.1 channels appeared no obvious difference when differentiating into foam cells (P>0.05); After being blocked specifically (rMargatoxin: 0.1, 10 nmol/L; BaC(12): 75, 125 micromol/L), the cellular contents of TC and CE were markedly reduced without exception and the ratios of CE/TC were all less than 50% (P<0.05).


CONCLUSIONS
Both Kv1.3 and Kir2.1 channels play a critical role in differentiation of macrophages into foam cells and blockage of corresponding potassium channels would prevent the formation of the foam cells.
Lei
Xin-jun
XJ
Department of Cardiology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, China.
Ma
Ai-qun
AQ
Xi
Yu-tao
YT
Zhang
Wei
W
Yao
Yan
Y
Du
Yuan
Y
D017609:Barium Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology*; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D012604:Scorpion Venoms / Q000494:pharmacology
D017609:Barium Compounds; D002712:Chlorides; D002788:Cholesterol Esters; C489461:Kir2.1 channel; D051664:Kv1.3 Potassium Channel; D024661:Potassium Channels, Inwardly Rectifying; D012604:Scorpion Venoms; C024986:barium chloride; C077910:margatoxin