Liver X receptor signaling pathways in cardiovascular disease.
The liver X receptors alpha and beta (LXRalpha and LXRbeta) are members of the nuclear receptor family of proteins that are critical for the control of lipid homeostasis in vertebrates. The endogenous activators of these receptors are oxysterols and intermediates in the cholesterol biosynthetic pathway. LXRs serve as cholesterol sensors that regulate the expression of multiple genes involved in the efflux, transport, and excretion of cholesterol. Recent studies have outlined the importance of LXR signaling pathways in the development of metabolic disorders such as hyperlipidemia and atherosclerosis. Synthetic LXR agonists inhibit the development of atherosclerosis in murine models, an effect that is likely to result from the modulation of both metabolic and inflammatory gene expression. These observations identify the LXR pathway as a potential target for therapeutic intervention in human cardiovascular disease.
Tontonoz
Peter
P
Howard Hughes Medical Institute, University of California, Los Angeles School of Medicine, Box 951662, Los Angeles, California 90095-1662, USA. ptontonoz@mednet.ucla.edu
Mangelsdorf
David J
DJ
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000503:physiopathology* / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018528:ATP-Binding Cassette Transporters; D001053:Apolipoproteins; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol