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Selected Publication:
Claudel, T; Leibowitz, MD; Fiévet, C; Tailleux, A; Wagner, B; Repa, JJ; Torpier, G; Lobaccaro, JM; Paterniti, JR; Mangelsdorf, DJ; Heyman, RA; Auwerx, J.
Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor.
Proc Natl Acad Sci U S A. 2001; 98(5):2610-2615
Doi: 10.1073/pnas.041609298
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- Leading authors Med Uni Graz
- Claudel Thierry
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- Abstract:
- A common feature of many metabolic pathways is their control by retinoid X receptor (RXR) heterodimers. Dysregulation of such metabolic pathways can lead to the development of atherosclerosis, a disease influenced by both systemic and local factors. Here we analyzed the effects of activation of RXR and some of its heterodimers in apolipoprotein E -/- mice, a well established animal model of atherosclerosis. An RXR agonist drastically reduced the development of atherosclerosis. In addition, a ligand for the peroxisome proliferator-activated receptor (PPAR)gamma and a dual agonist of both PPARalpha and PPARgamma had moderate inhibitory effects. Both RXR and liver X receptor (LXR) agonists induced ATP-binding cassette protein 1 (ABC-1) expression and stimulated ABC-1-mediated cholesterol efflux from macrophages from wild-type, but not from LXRalpha and beta double -/-, mice. Hence, activation of ABC-1-mediated cholesterol efflux by the RXR/LXR heterodimer might contribute to the beneficial effects of rexinoids on atherosclerosis and warrant further evaluation of RXR/LXR agonists in prevention and treatment of atherosclerosis.
- Find related publications in this database (using NLM MeSH Indexing)
- ATP-Binding Cassette Transporters - physiology
- Animals - physiology
- Apolipoproteins E - genetics
- Arteriosclerosis - genetics
- Biological Transport - genetics
- Cholesterol - metabolism
- Mice - metabolism
- Mice, Inbred C57BL - metabolism
- Mice, Knockout - metabolism
- Receptors, Retinoic Acid - metabolism
- Retinoid X Receptors - metabolism
- Transcription Factors - metabolism