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Liver X receptors as potential therapeutic targets in atherosclerosis Zhu Y; Li YClin Invest Med 2009[Oct]; 32 (5): E383-94PURPOSE: Atherosclerosis is the primary independent risk factor of cardiovascular disease, and Liver X Receptors (LXRalpha and LXRbeta) activation may play an anti-atherosclerosis effect. In this article, we summarize the current state of knowledge of roles of LXRs in physiology and homeostasis as well as the links between LXR action and atherosclerosis, and discuss the potential therapeutic effects of LXR agonists. SOURCE: A MEDLINE database search was performed to identify relevant articles using the keywords "liver X receptors", "LXRs", and "atherosclerosis". Additional papers were identified by a manual research of the references from the key articles. PRINCIPLE FINDINGS: Both LXR isoforms promote reverse cholesterol transport (RCT) and have anti-inflammatory activity. LXRalpha is the predominant receptor in the liver regulating triglyceride synthesis. The antiatherosclerotic ability of LXRs makes them attractive targets for drugs for the treatment of cardiovascular disease. However, LXR activation induces lipogenesis and hypertriglyceridemia. The first-generation synthetic ligands of LXR increase hepatic lipogenesis and plasma triglyceride levels. New LXR ligands need to be designed without undesirable side effects. CONCLUSION: LXR beta-selective agonists and LXR modulators, which act as agonists in macrophages and induce cholesterol efflux while as antagonists of lipogenesis in the liver, are two critical and attractive approaches to treat atherosclerosis and cardiovascular diseases.|Animals[MESH]|Atherosclerosis/drug therapy/*metabolism[MESH]|Cholesterol/metabolism[MESH]|Humans[MESH]|Lipogenesis/drug effects[MESH]|Liver X Receptors[MESH]|Orphan Nuclear Receptors/agonists/genetics/*metabolism[MESH] |
