Polybrominated Diphenyl Ether Quinone Exposure Induces Atherosclerosis Progression via CD36-Mediated Lipid Accumulation, NLRP3 Inflammasome Activation, and Pyroptosis

Polybrominated diphenyl ethers (PBDEs) are used worldwide in brominated flame retardants. Although due to the forbiddance of their application, PBDEs continuously exist in the environment due to their persistence. Therefore, it is important to expand the understanding of their potential toxicities and human risks. The underlying cardiovascular toxicological mechanisms of PBDEs are still largely unknown. Our previous studies indicated that PBDE quinone-type metabolite (PBDEQ) exposure causes reactive oxygen species (ROS)-driven cytotoxicity and various types of programmed cell death. Here, we first reported PBDEQ exposure induces atherosclerosis progression in bone marrow-derived macrophages (BMDMs) isolated from wild-type C57BL/6 or CD36(-/-) mice and J774A.1 macrophage models. First, we found that PBDEQ exposure induced lipid accumulation in oxidized low-density lipid (Ox-LDL)-treated J774A.1 macrophages. Consistently, in J774A.1 macrophages, PBDEQ exposure resulted in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis. CD36, a scavenger receptor responsible for the mediation of Ox-LDL uptake, was upregulated upon PBDEQ treatment. On the contrary, genetic knockout of CD36 or CD36 silencing by small interfering RNA efficiently attenuates PBDEQ-promoted lipid accumulation in BMDMs and J774A.1 macrophages. These findings highlight the effect of CD36 on the cardiovascular toxicity of PBDEs, which provides a better understanding of the pro-atherosclerosis effect of PBDEs.

Automated summary

PBDEs are persistent environmental pollutants used as flame retardants. Exposure to PBDEQ leads to atherosclerosis progression by inducing lipid accumulation and activating NLRP3 inflammasome and pyroptosis. CD36 plays a crucial role in the cardiovascular toxicity of PBDEs.