Expression of the ATP-binding cassette transporter A1 (ABCA1) gene is induced by oxysterol-activated transcription factors liver X receptor α (LXRα, NR1H3) and LXRβ (NR1H2) and their heterodimeric partners, retinoid X receptors (RXR) via functional LXR response element (LXRE) (Costet P et al. 2000; 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 HDL particles (Vedhachalam C et a. 2007; Ignatova ID et al. 2013). MicroRNA (miR-144) was found to bind the 3'-untranslated region (3'UTR) of ABCA1 mRNA to prohibit translation and reduce ABCA1-mediated cholesterol efflux from hepatocytes (de Aguiar Vallim TQ et al. 2013). In the liver, the farnesoid X receptor (FXR or NR1H4) often acts in opposition to LXRs in the regulation of cholesterol homeostasis. Indeed, FXR activation increases miR-144 expression to decrease hepatic ABCA1 levels and reduce circulating HDL concentrations in mouse models (de Aguiar Vallim TQ et al. 2013). Further, overexpression of miR-144 in a human hepatoma cell line (Hep3B) resulted in a decrease in both ABCA1 protein and efflux of cholesterol to lipid-poor ApoA-I, in the absence of a change in ABCA1 mRNA (de Aguiar Vallim TQ et al. 2013). Hepatic ABCA1 activity is responsible for ~75% of circulating HDL levels (with adipose and intestine contributing to the remainder). While macrophage ABCA1 activity is important in limiting foam cell formation during atherogenesis, macrophage ABCA1-generated HDL particles are not sufficiently abundant to significantly impact the circulating HDL pool. Of note, FXR is not expressed in macrophages, thus FXR/miR-144 is unlikely to contribute greatly to foam cell formation in atherogenesis, but FXR/miR-144 will more dramatically alter circulating serum HDL concentrations through its actions in the liver (de Aguiar Vallim TQ et al. 2013).