| Autor: |
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 |
| Předmět: |
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| Zdroj: |
Nature Medicine; Jan2001, Vol. 7 Issue 1, p53, 6p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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