Targeting liver X receptor &bgr;β: a new therapeutic approach to prevent atherosclerosis?

Author: Parini Paolo   Gustafsson Jan-ÅÅke  

Publisher: Future Medicine

ISSN: 1746-0875

Source: Future Lipidology, Vol.2, Iss.6, 2007-12, pp. : 603-607

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Abstract

Evaluation of: Bradley MN, Hong C, Chen M et al.: Ligand activation of LXR &bgr;β reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR αα and ApoE. J. Clin. Invest. 117, 2337––2346 (2007). The increase in cardiovascular disease and its clinical complications occurs despite extensive use of effective drugs and, thus, development of new and complementary therapeutic approaches is urged. Liver X receptors (LXRs) are cholesterol sensors within cells and play a critical role in the modulation of lipid and lipoprotein metabolism. Reverse cholesterol transport, bile acid synthesis and intestinal cholesterol absorption are all positively affected by LXR activation. In mice, LXR agonists have demonstrated beneficial effects on atherosclerosis, but also resulted in unfavorable effects on triglyceride metabolism, mainly due to the activation of LXRαα in the liver. Activation of LXR&bgr;β reduces atherosclerosis and increases HDL cholesterol, without raising plasma triglyceride levels, making it an attractive therapeutic target.