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Molecular Interventions 4:254-257, (2004)
© American Society for Pharmacology and Experimental Therapeutics
10.1124/mi.4.5.5
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Viewpoint

Combating Atherosclerosis With LXR{alpha} And PPAR{alpha} Agonists: Is Rational Multitargeted Polypharmacy the Future of Therapeutics in Complex Diseases?

Tomoshige Kino and George P. Chrousos

Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892

SUMMARY

The development of atherosclerosis can, in the absence of intervention, lead to cardiovascular disease, which is responsible for the demise of more Americans per year than any other disease. Beyer and colleagues report, in the Journal of Pharmacology and Experimental Therapeutics, that treating mice with a liver X receptor (LXR) agonist increases not only the concentration of circulating high-density lipoprotein (HDL) but also, unfortunately, that of circulating triglycerides. When doubly treated with LXR agonists together with peroxisome proliferator–activated receptor {alpha}(PPAR{alpha}) agonists, mice exhibited reduced concentrations of circulating triglycerides (but interestingly, triglyceride concentrations in the liver were not reduced) while their HDL concentrations remained elevated. The authors suggest that activation of both receptors, through the development and use of LXR{alpha}–PPAR{alpha} dual agonists, might become a useful therapy to bolster HDL levels while simultaneously suppressing circulating triglycerides in patients.




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Copyright © 2004 by the American Society for Pharmacology and Experimental Therapeutics.