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PMID: 20631351 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Liver x receptor signaling pathways and atherosclerosis.

Arteriosclerosis, thrombosis, and vascular biology ·Vol. 30 ·No. 8 ·2010-08-00 ·Pages 1513-8

Calkin AC, Tontonoz P

Abstract

First discovered as orphan receptors, liver X receptors (LXRs) were subsequently identified as the nuclear receptor target of the cholesterol metabolites, oxysterols. There are 2 LXR receptors encoded by distinct genes: LXRalpha is most highly expressed in the liver, adipose, kidney, adrenal tissues, and macrophages and LXRbeta is ubiquitously expressed. Despite differential tissue distribution, these isoforms have 78% homology in their ligand-binding domain and appear to respond to the same endogenous ligands. Work over the past 10 years has shown that the LXR pathway regulates lipid metabolism and inflammation via both the induction and repression of target genes. Given the importance of cholesterol regulation and inflammation in the development of cardiovascular disease, it is not surprising that activation of the LXR pathway attenuates various mechanisms underlying atherosclerotic plaque development. In this brief review, we will discuss the impact of the LXR pathway on both cholesterol metabolism and atherosclerosis.

MeSH Terms
Animals Atherosclerosis/immunology,metabolism,prevention & control Biological Transport Cardiovascular Agents/pharmacology Cholesterol/metabolism Endothelial Cells/metabolism Humans Inflammation Mediators/metabolism Ligands Liver X Receptors Macrophages/metabolism Muscle, Smooth, Vascular/metabolism Orphan Nuclear Receptors/agonists,metabolism Signal Transduction/drug effects
Chemicals
Cardiovascular Agents Inflammation Mediators Ligands Liver X Receptors NR1H3 protein, human Orphan Nuclear Receptors Cholesterol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Calkin Anna C
Howard Hughes Medical Institute, University of California at Los Angeles, School of Medicine, Box 951662, Los Angeles, CA 90095-1662, USA.
Tontonoz Peter
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Article Info
Journal
Arteriosclerosis, thrombosis, and vascular biology
Abbr.
Arterioscler Thromb Vasc Biol
ISSN
1524-4636
DOI
10.1161/ATVBAHA.109.191197
Published
2010-08-00
Pages
1513-8
Language
English
Region
United States
NLM ID
9505803
PMCID
PMC2919217
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NHLBI NIH HHS · R01 HL066088 · United States
NHLBI NIH HHS · R01 HL066088-10 · United States
External Links
PubMed source DOI: 10.1161/ATVBAHA.109.191197 PMC Full Text View journal details
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