Inhibiting NF-κB increases cholesterol efflux from THP-1 derived-foam cells treated with AngⅡ via up-regulating the expression of ATP-binding cassette transporter A1

摘要

Objective: To study the role of nuclear factor-kappa B(NF-κB) in cholesterol efflux from THP-1 derived-foam cells treated with AngiotensinⅡ(AngⅡ). Methods:Cultured THP-1 derived-foam cells were treated with AngⅡ or preincubated with tosyl-phenylalanine chloromethyl-ketone(TPCK) NF-κB inhibitor. The levels of activated NF-κB in the cells were examined by sandwich ELISA. Cellular cholesterol content was studied by electron microscopy scanning and zymochemistry via fluorospectrophotometer and cholesterol efflux was detected by scintillation counting technique. ABCA1 mRNA and protein were quantified by RT-PCR and Western blotting. Results:Addition of TPCK to the cells before AngⅡ stimulation attenuated the response of NF-κB p65 nuclear translocation induced by AngⅡ and showed no peak in foam cells group and caused a reduction in cholesterol content and an increase in cholesterol efflux by 24.1%(P < 0.05) and 41.1%(P < 0.05) respectively,when compared with AngⅡgroup. In accordance,the ABCA1 mRNA and protein were increased by 30% and 19%(P < 0.05) respectively,when compared with AngⅡ group. Conclusion:AngⅡ can down-regulate ABCA1 in THP-1 derived-foam cells via NF-κB,which leads to less cholesterol efflux and the increase of cholesterol content with the consequence of the promotion of atherosclerosis.