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Activation Of Liver X Receptor-Beta Lowers Cholesterol And Reverses Atherosclerosis

Date:
July 30, 2007
Source:
Journal of Clinical Investigation
Summary:
A new study shows that activation of LXR-beta by a synthetic compound is able to reverse atherosclerosis and cholesterol overload in mice.
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In animals and humans, the proteins known as liver X receptors (LXRs) sense cholesterol levels. Upon sensing increases in cholesterol, these receptors activate signaling pathways that remove diet-derived cholesterol from the body. Two types of LXRs – LXR-alpha and LXR-beta – are therefore potential targets for the development of anti-atherosclerosis drugs.

However, the effects of synthetic drugs that activate these two receptors have not been well studied.

In a study appearing online on July 26 in advance of publication in the August print issue of the Journal of Clinical Investigation, Peter Tontonoz and colleagues from the University of California, Los Angeles, show that activation of LXR-beta by a synthetic compound is able to reverse atherosclerosis and cholesterol overload in mice.

The authors began by studying mice lacking apolipoprotein E (apoE; a protein that functions in cholesterol distribution among cells), which have increased cholesterol levels and are predisposed to develop atherosclerosis. They showed that the loss of LXR-alpha in these animals results in a striking body-wide accumulation of cholesterol and accelerated atherosclerosis.

This observation suggests that LXR-beta alone is unable to maintain homeostasis under conditions of cholesterol overload. Surprisingly, however, administration of a synthetic compound that activates LXR-beta, was able to compensate for the loss of LXR-alpha, reduce cholesterol overload and reduce atherosclerosis.

The results of the study suggests that LXR-alpha has an essential role in maintaining cholesterol homeostasis in conditions of cholesterol overload such as hypercholesterolemia and lend support to the notion that future drug development studies should examine targeting LXR-beta.


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Journal of Clinical Investigation. "Activation Of Liver X Receptor-Beta Lowers Cholesterol And Reverses Atherosclerosis." ScienceDaily. ScienceDaily, 30 July 2007. <www.sciencedaily.com/releases/2007/07/070726185424.htm>.
Journal of Clinical Investigation. (2007, July 30). Activation Of Liver X Receptor-Beta Lowers Cholesterol And Reverses Atherosclerosis. ScienceDaily. Retrieved May 28, 2015 from www.sciencedaily.com/releases/2007/07/070726185424.htm
Journal of Clinical Investigation. "Activation Of Liver X Receptor-Beta Lowers Cholesterol And Reverses Atherosclerosis." ScienceDaily. www.sciencedaily.com/releases/2007/07/070726185424.htm (accessed May 28, 2015).

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