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Mediator 1 (MED1;also known as PBP or TRAP220), a key subunit of the Mediator complex, functions as a coactivator for PPARs and other transcriptional activators.Because PPARs play important roles in lipid metabolism, inflammation, and atherosclerosis, it becomes urgent to assess the function of MED1 in atherosclerosis.In the current study, to investigate the contribution of macrophage MED1 expression on atherogenesis in vivo, we generated macrophage-specific MED 1 knockout (MED 1 △ Mac) mice.Low-density lipoprotein (LDL) receptor deficient (LDLR-/-) mice were reconstituted with bone marrow from MED 1 △ Mac or MED1fl/fl mice and challenged with a high-fat diet.No differences were found in serum lipids between recipients reconstituted with MED1 △Mac and wild-type marrow.MED1 △Mac-LDLR-/-mice had the larger atherosclerotic lesions in the distal aorta than MED1fl/fl-LDLR-/-mice.Peritoneal macrophages from MED1 △Mac mice had increased uptake of oxidized LDL.Furthermore, MED1 △Mac macrophages had significantly increased mRNA expression levels of inflammatory genes, including COX-2, IL1 β, IL6, MCP1 and Grol compared with wild-type macrophages (P<0.01).These data demonstrate that MED 1 expression by macrophages has antiatherogenic effects via modulation of inflammatory activity and MED1 may be considered as a potential therapeutic target to treat atherosclerosis.