METTL3 (Methyltransferase Like 3)-Dependent N6-Methyladenosine Modification on <i>Braf</i> mRNA Promotes Macrophage Inflammatory Response and Atherosclerosis in Mice

Background: Atherosclerosis is a chronic inflammatory disease, in which macrophages determine the progression of atherosclerotic plaques. However, no studies have investigated how METTL3 (methyltransferase like 3) in macrophages affects atherosclerotic plaque formation in vivo. Additionally, whether Braf mRNA is modified by METTL3-dependent N6-methyladenosine (m6A) methylation remains unknown. Methods: We analyzed single-cell sequencing data of atherosclerotic plaques in mice fed with a high fat diet for different periods. Mettl3 fl/fl Lyz 2 cre Apoe –/– mice and littermate control Mettl3 fl/fl Apoe –/– mice were generated and fed high fat diet for 14 weeks. In vitro, we stimulated peritoneal macrophages with ox-LDL (oxidized low-density lipoprotein) and tested the mRNA and protein expression levels of inflammatory factors and molecules regulating ERK (extracellular…