Nuclear receptors as potential targets for modulating reverse cholesterol transport.
This review describes the role of nuclear receptors in the regulation of genes involved in cholesterol transport and synthetic modulators of these receptors. Increasing the efflux of cholesterol from peripheral cells, such as lipid-laden macrophages, through a process called reverse cholesterol transport (RCT) requires HDL. Increasing the circulating levels of HDL, as well as the efficiency of the RCT process, could result in a reduction in the development of coronary artery disease and atherosclerosis. Nuclear receptors of the RXR heterodimer family have recently been shown to regulate key genes involved in HDL metabolism and reverse cholesterol transport. These include the PPARs (peroxisome proliferator activated receptors), the LXR (liver X receptor) and the farnesoid X receptor (FXR). The synthesis of specific and potent ligands for these receptors has aided in ascertaining the physiological role of these receptors as lipid sensors and the potential therapeutic utility of modulators of these receptors in dyslipidemias and cardiovascular disease.
Pelton
Patricia D
PD
Department of Drug Discovery, Endocrine Therapeutics and Metabolic Diseases, Johnson & Johnson Pharmaceutical Research and Development, LLC., 1000 Route 202, Raritan, NJ 08869, USA. Ppelton@prdus.jnj.com
Patel
Mona
M
Demarest
Keith T
KT
D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D002784:Cholesterol; D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated