F-53B stimulated vascular smooth muscle cell phenotypic switch and vascular remodeling via ferroptosis-related pathway

The compound 6:2 chlorinated polyfluorinated ether sulfonate (F53B), an alternative to perfluorooctane sulfonate (PFOS), has been widely utilized in China. Although the connection between the exposure and toxicity of F53B is established, the role and mechanisms of the compound in promoting vascular remodeling are yet to be elucidated. Thus, the present study investigated the impact of F53B on the function of vascular smooth muscle cells (VSMCs) and vascular remodeling. The data exhibited that F53B stimulates vascular morphological alterations in vivo, and exposure to the compound caused excessive VSMCs ferroptosis and phenotype switching, as determined using phenotype and molecular assays. Moreover, Fer-1 reversed F-53B-induced VSMC dysfunction and vascular remodeling. Furthermore, F53B activated the ferroptosis-related pathway, encompassing ATR expression and LOC101929922/miR-542-3p/ACSL4 pathway. Thus, the current results elaborated on the multifaceted toxicities of F53B that induce vascular remodeling, thereby necessitating the assessment of vasotoxicity risks associated with the compound.