T0901317 or GW3965, two synthetic agonists of liver X-receptors (LXRα, NR1H3 and LXRβ, NR1H2) or cholesterol-loading significantly induced the expression of ABCA1 mRNA in mouse RAW 264.7 and human THP1 macrophage cell lines (Costet P et al. 2000; Venkateswaran A et al. 2000; Whitney KD et al. 2001; Jakobsson T et al. 2009). Similar regulation of ABCA1 mRNA expression by NR1H2, 3 agonists was observed in human peripheral blood-derived monocytes (Larrede S et al. 2009). Treatment with T0901317 increased expression of ABCA1 mRNA in variety of cells and tissues isolated from wild type but not LXR-/- mice (lacking both NR1H3 and NR1H2) (Repa JJ et al. 2000; Wagner BL et al. 2003). At the same time, NR1H2, 3 repressed basal expression of ABCA1 in a tissue-specific manner, occurring in macrophages and intestinal mucosa but not in several other mouse tissues (Wagner BL et al. 2003). Treatment of human THP-1 macrophages with endogenous (25-hydroxycholesterol) or synthetic (T0901317) ligands of NR1H2,3 stimulated both transcriptional and posttranscriptional events to enhance ABCA1 expression (Ignatova ID et al. 2013). NR1H2,3-induced expression of ABCA1 is thought to promote ABCA1-mediated cellular cholesterol transport across the plasma membrane to lipid-poor apolipoproteins, such as ApoA1 and ApoE in the generation of nascent high-density lipoproteins (HDL) particles (Ignatova ID et al. 2013; Vedhachalam C et a. 2007). Loss of ABCA1 in humans results in Tangier disease, a condition in which patients have extremely low levels of circulating HDL, massive accumulation of cholesterol in macrophages, and an increased risk for developing atherosclerosis (Rust S et al. 1999).

Multiple microRNAs have been identified as regulators of ABCA1 mRNA levels (Horie T et al. 2010; Sun D et al. 2012; de Aguiar Vallim TQ et al. 2013).