Perfluorooctane sulfonate promotes atherosclerosis by modulating M1 polarization of macrophages through the NF-ΚB pathway

Perfluorooctane sulfonate (PFOS) is a widely used and distributed perfluorinated compounds and is reported to be harmful to cardiovascular health; however, the direct association between PFOS exposure and atherosclerosis and the underlying mechanisms remain unknown. Therefore, this study aimed to investigate the effects of PFOS exposure on the atherosclerosis progression and the underlying mechanisms. PFOS was administered through oral gavage to apolipoprotein E-deficient (ApoE-/-) mice for 12 weeks. PFOS exposure significantly increased pulse wave velocity (PWV) and intima-media thickness (IMT), increased aortic plaque burden and vulnerability, and elevated serum lipid and inflammatory cytokine levels. PFOS promoted aortic and RAW264.7 M1 macro-phage polarization, which increased the secretion of nitric oxide synthase (iNOS) and pro-inflammatory factors (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], and interleukin-1 beta [IL-1 beta]), and suppressed M2 macro-phage polarization, which decreased the expression of CD206, arginine I (Arg-1), and interleukin-10 (IL-10). Moreover, PFOS activated nuclear factor-kappa B (NF-kappa B) in the aorta and macrophages. BAY11-7082 was used to inhibit NF-kappa B-alleviated M1 macrophage polarization and the inflammatory response induced by PFOS in RAW264.7 macrophages. Our results are the first to reveal the acceleratory effect of PFOS on the atherosclerosis progression in ApoE-/-mice, which is associated with the NF-kappa B activation of macrophages to M1 polarization to induce inflammation.

Automated summary

This study aimed to investigate the effects of PFOS exposure on atherosclerosis progression and the underlying mechanisms. The results showed that PFOS increased pulse wave velocity, intima-media thickness, aortic plaque burden, and levels of serum lipids and inflammatory cytokines. PFOS promoted M1 macrophage polarization and suppressed M2 macrophage polarization, leading to inflammation. NF-κB activation in macrophages was associated with this process. These findings highlight the role of PFOS in accelerating atherosclerosis progression through NF-κB-mediated inflammation.