LXR agonists for the treatment of atherosclerosis.

Liver X receptor (LXR) alpha/beta nuclear receptors are intracellular sterol sensors that regulate expression of genes controlling cholesterol absorption, excretion, catabolism and cellular efflux in target organs, including small intestine, liver and macrophages. Through co-ordination of the expression of target genes in multiple tissues, LXR agonists increase the flux of cholesterol from the periphery to the liver, where it is metabolized and excreted into the bile. Synthetic dual LXR alpha/beta agonists decrease atherosclerosis in mice, however, upregulation of lipogenic target genes and triglyceride elevation in rodents reveals a narrow therapeutic window. LXR subtype-selective agonists or LXR modulators may dissociate the anti-atherosclerotic and lipogenic effects of current dual LXR agonists.