Brominated Flame Retardants Exposure Promotes the Formation of Atherosclerotic Plaque in Aortic Roots of ApoE–/– Mice by Increasing Macrophage Recruitment and Foam Cell Formation

Brominated flame retardants (BFRs) are persistent organic pollutants worldwide. However, the effect of BFRs on the development of atherosclerosis is currently unknown. Here we aimed to investigate the effects of three typical BFRs (BDE-47, BDE-209, and DBDPE) on the development of atherosclerosis and explored the underlying mechanisms using an in vitro cell model and ApoE^–/– mice. Our data showed that BFRs significantly inhibited the viability of human aortic endothelial cells (HAECs) and induced the generation of ROS. BFRs significantly enhanced the content of Ox-LDL in THP-1 macrophages, which promoted the formation of foam cells. In an in vivo study, BFRs exposure significantly increased the plaque area and lipid content in the aortic root of mice. BFRs significantly increased the ROS level in plaques and promoted the expression level of adhesion molecule ICAM-1, which enhanced the recruitment of macrophages. Transcriptome analysis showed that differentially expressed genes (DEGs) were significantly enriched in signaling pathways related to oxidative stress and lipid metabolism. In summary, these results indicate that BFRs exposure can promote the development of atherosclerosis by increasing macrophage recruitment and foam cell formation, which elucidates the impact of BFRs on atherosclerosis for the first time, and provide scientific clues for the prevention and treatment of atherosclerosis.