We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
PPAR-a and PPAR-? activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway.
- Authors
Chinetti, Giulia; Lestavel, Sophie; Bocher, Virginie; Remaley, Alan T.; Neve, Bernadette; Torra, Ines Pineda; Teissier, Elisabeth; Minnich, Anne; Jaye, Michael; Duverger, Nicolas; Brewer, H. Bryan; Fruchart, Jean-Charles; Clavey, Veronique; Staels, Bart
- Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-a and PPAR-? are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-a may promote foam-cell formation by inducing expression of the macrophage scavenger receptor CD36. This prompted us to investigate the influence of different PPAR- activators on cholesterol metabolism and foam-cell formation of human primary and THP-1 macrophages. Here we show that PPAR-a and PPAR-? activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-a and PPAR-? activators induce the expression of the gene encoding ABCA1, a transporter that controls apoAI-mediated cholesterol efflux from macrophages. These effects are likely due to enhanced expression of liver-x-receptor a, an oxysterol-activated nuclear receptor which induces ABCA1- promoter transcription. Moreover, PPAR-a and PPAR-? activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-a or PPAR-? activation does not influence cholesterol efflux from macrophages isolated from patients with Tangier disease, which is due to a genetic defect in ABCA1. Here we identify a regulatory role for PPAR-a and PPAR-? in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages.
- Subjects
PEROXISOMES; MACROPHAGES; CHOLESTEROL; CELLS
- Publication
Nature Medicine, 2001, Vol 7, Issue 1, p53
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/83348