| First Author | Yu M | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 33 | Pages | 16977-89 |
| PubMed ID | 27358406 | Mgi Jnum | J:338770 |
| Mgi Id | MGI:6832090 | Doi | 10.1074/jbc.M116.740092 |
| Citation | Yu M, et al. (2016) Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen: A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR)gamma-DEPENDENT MECHANISM. J Biol Chem 291(33):16977-89 |
| abstractText | Macrophage CD36 binds and internalizes oxidized low density lipoprotein (oxLDL) to facilitate foam cell formation. CD36 expression is activated by peroxisome proliferator-activated receptor gamma (PPARgamma). Tamoxifen, an anti-breast cancer medicine, has demonstrated pleiotropic functions including cardioprotection with unfully elucidated mechanisms. In this study, we determined that treatment of ApoE-deficient mice with tamoxifen reduced atherosclerosis, which was associated with decreased CD36 and PPARgamma expression in lesion areas. At the cellular level, we observed that tamoxifen inhibited CD36 protein expression in human THP-1 monocytes, THP-1/PMA macrophages, and human blood monocyte-derived macrophages. Associated with decreased CD36 protein expression, tamoxifen reduced cellular oxLDL accumulation in a CD36-dependent manner. At the transcriptional level, tamoxifen decreased CD36 mRNA expression, promoter activity, and the binding of the PPARgamma response element in CD36 promoter to PPARgamma protein. Tamoxifen blocked ligand-induced PPARgamma nuclear translocation and CD36 expression, but it increased PPARgamma phosphorylation, which was due to that tamoxifen-activated ERK1/2. Furthermore, deficiency of PPARgamma expression in macrophages abolished the inhibitory effect of tamoxifen on CD36 expression or cellular oxLDL accumulation both in vitro and in vivo Taken together, our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARgamma signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen. |
