Oxidized LDL upregulated ATP binding cassette transporter-1 in THP-1 macrophages

AIM: To study the effect of oxidized low density lipoprotein (ox-LDL) on ATP binding cassette transporter A1(ABCA1) in THP-1 macrophages. METHODS: After exposing the cultured THP-1 macrophages to ox-LDL fordifferent periods, cholesterol efflux was determined by FJ-2107P type liquid scintillator. ABCA1 mRNA and proteinlevel were determined by reverse trancriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively.The cholesterol level in THP-1 macrophage foam cells was detected by high performance liquid chromatography.RESULTS: ox-LDL elevated ABCA1 in both protein and mRNA levels and increased apolipoprotein (apo) A-I-medi-ated cholesterol efflux in a time- and dose-dependent manner. 22(R)-hydroxycholesterol and 9-cis-retinoic acid didsignificantly increase cholesterol efflux in THP-1 macrophage foam cells (P<0.05), respectively. Both of themfurther promoted cholesterol efflux (P<0.01). As expected, liver X receptor (LXR) agonist decreased content ofesterified cholesterol in the macrophage foam cells compared with control, whereas only a slight decrease of freecholesterol was observed. LXR activity was slightly increased by oxidized LDL by 12 % at 12 h compared with 6 h.However, LXR activity was increased about 1.8 times at 24 h, and oxidized LDL further increased LXR activity byabout 2.6 times at 48 h. CONCLUSION: ABCA1 gene expression was markedly increased in cholesterol-loadedcells as a result of activation of LXR/RXR. ABCA1 plays an important role in the homeostasis of cholesterol in themacrophages.