| First Author | Bai L | Year | 2017 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 37 |
| Issue | 8 | Pages | 1470-1481 |
| PubMed ID | 28642237 | Mgi Jnum | J:269233 |
| Mgi Id | MGI:6272147 | Doi | 10.1161/ATVBAHA.117.309672 |
| Citation | Bai L, et al. (2017) Mediator 1 Is Atherosclerosis Protective by Regulating Macrophage Polarization. Arterioscler Thromb Vasc Biol 37(8):1470-1481 |
| abstractText | OBJECTIVE: MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated. APPROACH AND RESULTS: To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1(DeltaMac)/ApoE(-)(/-)) mice and found that atherosclerosis was greater in MED1(DeltaMac)/ApoE(-/-) mice than in MED1(fl/fl)/ApoE(-/-) littermates. The gene expression of M1 markers was increased and that of M2 markers decreased in both aortic wall and peritoneal macrophages from MED1(DeltaMac)/ApoE(-/-) mice, whereas MED1 overexpression rectified the changes in M1/M2 expression. Moreover, LDLR (low-density lipoprotein receptor)-deficient mice received bone marrow from MED1(DeltaMac) mice showed greater atherosclerosis. Mechanistically, MED1 ablation decreased the binding of PPARgamma (peroxisome proliferator-activated receptor gamma) and enrichment of H3K4me1 and H3K27ac to upstream region of M2 marker genes. Furthermore, interleukin 4 induction of PPARgamma and MED1 increased the binding of PPARgamma or MED1 to the PPAR response elements of M2 marker genes. CONCLUSIONS: Our data suggest that MED1 is required for the PPARgamma-mediated M2 phenotype switch, with M2 marker genes induced but M1 marker genes suppressed. MED1 in macrophages has an antiatherosclerotic role via PPARgamma-regulated transactivation. |
