| First Author | Jiang M | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 482 |
| Issue | 4 | Pages | 849-856 |
| PubMed ID | 27890613 | Mgi Jnum | J:241683 |
| Mgi Id | MGI:5903368 | Doi | 10.1016/j.bbrc.2016.11.123 |
| Citation | Jiang M, et al. (2017) Activation of PPARgamma does not contribute to macrophage ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI. Biochem Biophys Res Commun 482(4):849-856 |
| abstractText | Activation of macrophage ABCA1/G1 expression and cholesterol efflux is believed one of the mechanisms by which PPARgamma inhibits atherosclerosis. PPARgamma can also activate CD36 expression, a receptor for oxLDL, which may supply LXR ligands to activate LXR-ABCA1/G1 pathways. However, the controversial effects of PPARgamma on ABCA1 expression have been reported. In this study, we used peritoneal macrophages isolated from wild type and CD36 deficient (CD36-/-) mice to clarify if PPARgamma ligands can influence ABCA1 expression by CD36 function. We found that CD36 deficiency had no effect on cholesterol efflux and ABCA1/ABCG1 expression at basal levels. In both cell types, PPARgamma ligands (15d-PGJ2, troglitazone and pioglitazone) reduced ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI, with most by troglitazone. LXR ligand-induced ABCA1 expression and cholesterol efflux was attenuated by PPARgamma ligands. Associated with decreased ABCA1 protein levels, ABCA1 mRNA and promoter activity were reduced by PPARgamma ligands. Furthermore, high expressing PPARgamma reduced ABCA1 expression and LXR-activated ABCA1 promoter in a CD36-independent manner. In contrast, ABCG1 expression was induced by PPARgamma ligands while inhibited by PPARgamma inactivation. Taken together, our study suggests that enhancement of macrophage cholesterol metabolism by PPARgamma is not contributed by activating ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI, which is not involved by CD36 expression either. |
