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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1169.)
© 2003 American Heart Association, Inc.

ATVB In Focus

Liver X Receptor Agonists as Potential Therapeutic Agents for Dyslipidemia and Atherosclerosis

Erik G. Lund; John G. Menke; Carl P. Sparrow

From the Departments of Atherosclerosis and Endocrinology and Metabolic Research (J.G.M), Merck Research Laboratories, Rahway, NJ.

Correspondence to Erik G. Lund, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065. E-mail erik_lund{at}merck.com

Series Editor: Alan R. Tall
ATVB In Focus

Role of ABCA1 in Cellular Cholesterol Efflux and Reverse Cholesterol Transport

Previous Brief Reviews in this Series:

•Yancy PG, Bortnick AE, Kellner-Weibel G, de la Llera-Moya M, Phillips MC, Rothblat GH. Importance of different pathways of cellular cholesterol efflux. 2003;23:712–719.
•Oram JF, HDL Apolipoproteins and ABCA1: partners in the removal of excess cellular cholesterol. 2003;23:720–727.
•Joyce C, Freeman L, Brewer HB Jr, Sanatamarina-Fojo S. Study of ABCA1 function in transgenic mice. 2003;23:965–971.
•Aiello RJ, Brees D, Francone OL. ABCA1-deficient mice: insights into the role of monocyte lipid efflux in HDL formation and inflammation. 2003;23:972–980.

The recent identification of liver X receptors (LXR) as regulators of the cholesterol and phospholipid export pump ABCA1 has raised the possibility that LXR agonists could be developed as HDL-raising agents, possibly also acting on the artery wall to stimulate cholesterol efflux from lipid-laden macrophages. Presently several pharmaceutical companies are working to develop such compounds, which will require finding a path for separating these beneficial effects from the detrimental stimulation of triglyceride synthesis also inherent to LXR agonists. Other challenges to the drug development process include species differences, which makes prediction of in vivo effects of LXR agonists in humans difficult. This review summarizes the present state of knowledge on LXR as a drug target and discusses possible solutions for dissociating the favorable effects of LXR agonists from their unwanted effects.

Key Words: atherosclerosis • liver X receptor • HDL • triglycerides

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