Propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα signaling pathway in THP-1 macrophage-derived foam cells

Background: ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor-B1 (SR-B1) promote cholesterol efflux from cells to lipid-poor apolipoprotein A-I and play an important role in the development of atherosclerosis. Liver X receptor (LXR alpha) and peroxisome proliferator-activated receptor-gamma (PPAR gamma) operate as cholesterol sensors, which may protect from cholesterol overload by stimulating cholesterol efflux from cells to high-density lipoprotein through ABCA1, ABCG1, and SR-B1. Propofol administration is associated with cardiovascular protective effects, including anti-inflammatory and antioxidant properties. Here, we examined the effect of propofol on ABCA1, ABCG1, and SR-B1 expression and explored whether PPAR gamma and LXR alpha were involved in the regulation of propofol-induced ABCA1, ABCG1, and SR-B1 expression in THP-1 macrophage-derived foam cells. Methods and Results: Propofol significantly increased expression levels of ABCA1, ABCG1, and SR-B1 in a time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by propofol treatment. Moreover, PPAR gamma and LXR alpha were up-regulated by propofol treatment. In addition, the up-regulated expression of ABCA1, ABCG1, and SR-B1 by propofol was significantly abolished by both PPAR gamma siRNA and LXR alpha siRNA in THP-1 macrophage-derived foam cells. Conclusion: These results provide evidence that propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPAR gamma/LXR alpha pathway in THP-1 macrophage-derived foam cells. (C) 2014 Elsevier Inc. All rights reserved.