Liver X receptors in cardiovascular and metabolic disease.
Liver X receptors (LXRs) alpha and beta are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions in human cardiovascular and metabolic disease.
Geyeregger
R
R
Clin. Div. of Endocrinology and Metabolism, Dept. of Internal Med. III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Zeyda
M
M
Stulnig
T M
TM
D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D006801:Humans; D007107:Immune System / Q000502:physiology; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear