You are not currently logged in.
Access your personal account or get JSTOR access through your library or other institution:
If You Use a Screen ReaderThis content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Identification of Macrophage Liver X Receptors as Inhibitors of Atherosclerosis
Rajendra K. Tangirala, Eric D. Bischoff, Sean B. Joseph, Brandee L. Wagner, Robert Walczak, Bryan A. Laffitte, Chris L. Daige, Diane Thomas, Richard A. Heyman, David J. Mangelsdorf, Xuping Wang, Aldons J. Lusis, Peter Tontonoz and Ira G. Schulman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 99, No. 18 (Sep. 3, 2002), pp. 11896-11901
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3073135
Page Count: 6
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Preview not available
Recent studies have identified the liver X receptors (LXRα and LXRβ) as important regulators of cholesterol metabolism and transport. LXRs control transcription of genes critical to a range of biological functions including regulation of high density lipoprotein cholesterol metabolism, hepatic cholesterol catabolism, and intestinal sterol absorption. Although LXR activity has been proposed to be critical for physiologic lipid metabolism and transport, direct evidence linking LXR signaling pathways to the pathogenesis of cardiovascular disease has yet to be established. In this study bone marrow transplantations were used to selectively eliminate macrophage LXR expression in the context of murine models of atherosclerosis. Our results demonstrate that LXRs are endogenous inhibitors of atherogenesis. Additionally, elimination of LXR activity in bone marrow-derived cells mimics many aspects of Tangier disease, a human high density lipoprotein deficiency, including aberrant regulation of cholesterol transporter expression, lipid accumulation in macrophages, splenomegaly, and increased atherosclerosis. These results identify LXRs as targets for intervention in cardiovascular disease.
Proceedings of the National Academy of Sciences of the United States of America © 2002 National Academy of Sciences