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

Shasha Li; Dongyuan Bian; Hongqi Deng; Junkai Guo; Xiaobing Wu; Hao Liu; Rui Wen; Yiyan Li; Nan Liu; Suli Huang; Guimiao Lin

doi:10.1021/envhealth.4c00183

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

Environ Health (Wash). 2025 Mar 12;3(6):669-679. doi: 10.1021/envhealth.4c00183. eCollection 2025 Jun 20.

Authors

Shasha Li^{1

2}, Dongyuan Bian¹, Hongqi Deng¹, Junkai Guo¹, Xiaobing Wu³, Hao Liu¹, Rui Wen¹, Yiyan Li¹, Nan Liu⁴, Suli Huang¹, Guimiao Lin¹

Affiliations

¹ School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China.
² School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China.
³ Department of Cardio-Cerebrovascular and Diabetes Prevention and Control, Shenzhen Center for Chronic Disease Control, Shenzhen 518020, China.
⁴ Institute of Environment and Health, South China Hospital, Shenzhen University Medical School, Shenzhen 518116, China.

Abstract

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.

Keywords: Atherosclerosis; BDE-209; BDE-47; Brominated flame retardant; DBDPE; Persistent organic pollutant.