PPAR-[alpha] and PPAR-[gamma] activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-alpha may promote fo...
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| Veröffentlicht in: | Nature medicine 2001-01, Vol.7 (1), p.53 |
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| creator | Chinetti, Giulia Lestavel, Sophie Bocher, Virginie Remaley, Alan T Neve, Bernadette Inés Pineda Torra Teissier, Elisabeth Minnich, Anne Jaye, Michael Duverger, Nicolas Brewer, H Bryan Jean-Charles Fruchart Clavey, Véronique Staels, Bart |
| description | Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-alpha 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-alpha and PPAR-gamma activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-alpha and PPAR-gamma 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 alpha, an oxysterol-activated nuclear receptor which induces ABCA1-promoter transcription. Moreover, PPAR-alpha and PPAR-gamma activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-alpha or PPAR-gamma 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-alpha and PPAR-gamma in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages. |
| doi_str_mv | 10.1038/83348 |
| format | Article |
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PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-alpha 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-alpha and PPAR-gamma activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-alpha and PPAR-gamma 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 alpha, an oxysterol-activated nuclear receptor which induces ABCA1-promoter transcription. Moreover, PPAR-alpha and PPAR-gamma activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-alpha or PPAR-gamma 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-alpha and PPAR-gamma in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/83348</identifier><language>eng</language><publisher>New York: Nature Publishing Group</publisher><subject>Atherosclerosis ; Cholesterol ; Fatty acids ; Genes ; Genomics ; Ligands ; Lipids ; Metabolism ; Publishing</subject><ispartof>Nature medicine, 2001-01, Vol.7 (1), p.53</ispartof><rights>Copyright Nature Publishing Group Jan 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids></links><search><creatorcontrib>Chinetti, Giulia</creatorcontrib><creatorcontrib>Lestavel, Sophie</creatorcontrib><creatorcontrib>Bocher, Virginie</creatorcontrib><creatorcontrib>Remaley, Alan T</creatorcontrib><creatorcontrib>Neve, Bernadette</creatorcontrib><creatorcontrib>Inés Pineda Torra</creatorcontrib><creatorcontrib>Teissier, Elisabeth</creatorcontrib><creatorcontrib>Minnich, Anne</creatorcontrib><creatorcontrib>Jaye, Michael</creatorcontrib><creatorcontrib>Duverger, Nicolas</creatorcontrib><creatorcontrib>Brewer, H Bryan</creatorcontrib><creatorcontrib>Jean-Charles Fruchart</creatorcontrib><creatorcontrib>Clavey, Véronique</creatorcontrib><creatorcontrib>Staels, Bart</creatorcontrib><title>PPAR-[alpha] and PPAR-[gamma] activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway</title><title>Nature medicine</title><description>Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-alpha 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-alpha and PPAR-gamma activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-alpha and PPAR-gamma 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 alpha, an oxysterol-activated nuclear receptor which induces ABCA1-promoter transcription. Moreover, PPAR-alpha and PPAR-gamma activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-alpha or PPAR-gamma activation does not influence cholesterol efflux from macrophages isolated from patients with Tangier disease, which is due to a genetic defect in ABCA1. 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Bernadette</au><au>Inés Pineda Torra</au><au>Teissier, Elisabeth</au><au>Minnich, Anne</au><au>Jaye, Michael</au><au>Duverger, Nicolas</au><au>Brewer, H Bryan</au><au>Jean-Charles Fruchart</au><au>Clavey, Véronique</au><au>Staels, Bart</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PPAR-[alpha] and PPAR-[gamma] activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway</atitle><jtitle>Nature medicine</jtitle><date>2001-01-01</date><risdate>2001</risdate><volume>7</volume><issue>1</issue><spage>53</spage><pages>53-</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-alpha 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-alpha and PPAR-gamma activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-alpha and PPAR-gamma 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 alpha, an oxysterol-activated nuclear receptor which induces ABCA1-promoter transcription. Moreover, PPAR-alpha and PPAR-gamma activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-alpha or PPAR-gamma 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-alpha and PPAR-gamma in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages.</abstract><cop>New York</cop><pub>Nature Publishing Group</pub><doi>10.1038/83348</doi></addata></record> |
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| source | SpringerLink Journals; Nature Journals Online |
| subjects | Atherosclerosis Cholesterol Fatty acids Genes Genomics Ligands Lipids Metabolism Publishing |
| title | PPAR-[alpha] and PPAR-[gamma] activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway |
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