Liver X receptors as therapeutic targets in metabolism and atherosclerosis.

The liver X receptors (LXRs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Since their initial identification more than a decade ago, LXRs have been characterized as key transcriptional regulators of lipid and carbohydrate homeostasis. LXRs are activated by the intracellular accumulation of cholesterol derivatives to stimulate cholesterol efflux and reverse cholesterol transport and excretion into the bile. Glucose functions as an LXR ligand in carbohydrate metabolism, and receptor agonism suppresses hepatic gluconeogenesis and improves insulin sensitivity. In addition to these beneficial metabolic effects, LXR ligands suppress inflammatory and proliferative responses of vascular cells and prevent the development of atherosclerosis and its complications. In this review, we summarize the important roles of LXRs in metabolism and vascular biology and discuss their implications as potential molecular drug targets for the treatment of cardiovascular diseases.