Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. Export

@article{citeulike:279858, abstract = {OBJECTIVE: Complications of atherosclerotic cardiovascular disease due to elevated blood cholesterol levels are the major cause of death in the Western world. The liver X receptors, LXRalpha and LXRbeta (LXRs), are ligand-dependent transcription factors that act as cholesterol sensors and coordinately control transcription of genes involved in cholesterol and lipid homeostasis as well as macrophage inflammatory gene expression. LXRs regulate cholesterol balance through activation of ATP-binding cassette transporters that promote cholesterol transport and excretion from the liver, intestine, and macrophage. Although LXR agonists are known to delay progression of atherosclerosis in mouse models, their ability to abrogate preexisting cardiovascular disease by inducing regression and stabilization of established atherosclerotic lesions has not been addressed. METHODS AND RESULTS: We demonstrate that LXR agonist treatment increases ATP-binding cassette transporter expression within preexisting atherosclerotic lesions, resulting in regression of these lesions as well as remodeling from vulnerable to stable lesions and a reduction in macrophage content. Further, using macrophage-selective LXR-deficient mice created by bone marrow transplantation, we provide the first evidence that macrophage LXR expression is necessary for the atheroprotective actions of an LXR agonist. CONCLUSIONS: These data substantiate that drugs targeting macrophage LXR activity may offer therapeutic benefit in the treatment of atherosclerotic cardiovascular disease.}, address = {X-Ceptor Therapeutics Inc, San Diego, Calif 92121, USA.}, author = {Levin, N. and Bischoff, E. D. and Daige, C. L. and Thomas, D. and Vu, C. T. and Heyman, R. A. and Tangirala, R. K. and Schulman, I. G.}, citeulike-article-id = {279858}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/01.ATV.0000150044.84012.68}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15539622}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15539622}, doi = {10.1161/01.ATV.0000150044.84012.68}, issn = {1524-4636}, journal = {Arterioscler Thromb Vasc Biol}, keywords = {ffa, insulinresistance, lxra}, month = {January}, number = {1}, pages = {135--142}, posted-at = {2005-08-12 08:46:12}, priority = {2}, title = {Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists.}, url = {http://dx.doi.org/10.1161/01.ATV.0000150044.84012.68}, volume = {25}, year = {2005} }

TY - JOUR ID - citeulike:279858 L3 - citeulike-article-id:279858 N2 - OBJECTIVE: Complications of atherosclerotic cardiovascular disease due to elevated blood cholesterol levels are the major cause of death in the Western world. The liver X receptors, LXRalpha and LXRbeta (LXRs), are ligand-dependent transcription factors that act as cholesterol sensors and coordinately control transcription of genes involved in cholesterol and lipid homeostasis as well as macrophage inflammatory gene expression. LXRs regulate cholesterol balance through activation of ATP-binding cassette transporters that promote cholesterol transport and excretion from the liver, intestine, and macrophage. Although LXR agonists are known to delay progression of atherosclerosis in mouse models, their ability to abrogate preexisting cardiovascular disease by inducing regression and stabilization of established atherosclerotic lesions has not been addressed. METHODS AND RESULTS: We demonstrate that LXR agonist treatment increases ATP-binding cassette transporter expression within preexisting atherosclerotic lesions, resulting in regression of these lesions as well as remodeling from vulnerable to stable lesions and a reduction in macrophage content. Further, using macrophage-selective LXR-deficient mice created by bone marrow transplantation, we provide the first evidence that macrophage LXR expression is necessary for the atheroprotective actions of an LXR agonist. CONCLUSIONS: These data substantiate that drugs targeting macrophage LXR activity may offer therapeutic benefit in the treatment of atherosclerotic cardiovascular disease. IS - 1 JF - Arterioscler Thromb Vasc Biol SN - 1524-4636 AD - X-Ceptor Therapeutics Inc, San Diego, Calif 92121, USA. EP - 142 TI - Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. VL - 25 SP - 135 KW - ffa KW - insulinresistance KW - lxra AU - Levin, N AU - Bischoff, ED AU - Daige, CL AU - Thomas, D AU - Vu, CT AU - Heyman, RA AU - Tangirala, RK AU - Schulman, IG PY - 2005/01// UR - http://dx.doi.org/10.1161/01.ATV.0000150044.84012.68 ER -