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

• DOI: 10.1016/j.carpath.2014.12.004
• Publication Date: 2014-12-27T00:45:13Z
• Authors: Xin Ma; Shu-Fen Li; Zai-Sheng Qin; Jing Ye; Zhen-Long Zhao; Hai-Hong Fang; Zhi-Wen Yao; Miao-Ning Gu; Yan-Wei Hu
• Keywords: 0303 health sciences; Time Factors; Anticholesteremic Agents; Scavenger Receptors, Class B; Orphan Nuclear Receptors; Transfection; Cell Line; Up-Regulation; PPAR gamma; 03 medical and health sciences; Cholesterol; Humans; ATP-Binding Cassette Transporters; RNA Interference; RNA, Messenger; Propofol; ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; Foam Cells; Liver X Receptors; Signal Transduction

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 (LXRα) and peroxisome proliferator-activated receptor-gamma (PPARγ) 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 PPARγ and LXRα were involved in the regulation of propofol-induced ABCA1, ABCG1, and SR-B1 expression in THP-1 macrophage-derived foam cells.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, PPARγ and LXRα 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 PPARγ siRNA and LXRα siRNA in THP-1 macrophage-derived foam cells.These results provide evidence that propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα pathway in THP-1 macrophage-derived foam cells.