PFOS and Its Substitute OBS Cause Endothelial Dysfunction to Promote Atherogenesis in ApoE<sup>–/–</sup> Mice
Boxiang Zhang, Qing Li, Wensheng Wang, Mingxing Tian, Dan Xu, Ying Xie
Abstract
High Resolution Image Download MS PowerPoint Slide Perfluorooctanesulfonate (PFOS), an emerging contaminant with widespread concern, has been associated with the pathogenesis of atherosclerosis (AS). As a substitute for PFOS, sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is extensively utilized in various applications and detected in human blood. However, its potential health risk in AS remain unclear. In this study, we investigated the comparative impacts of PFOS and OBS on endothelial dysfunction and atherogenesis. In the in vivo study, Apolipoprotein E knockout (ApoE –/– ) mice were exposed to 0.4 or 4 mg/L PFOS/OBS for 12 weeks. We found that dyslipidemia developed more rapidly in the OBS-exposed mice than in the PFOS-exposed mice. PFOS exhibited a higher enrichment capacity in both blood and aortic tissues than OBS. Remarkably, OBS induced a more pronounced inflammatory response and caused a more significant disruption of the endothelial barrier in the aorta of ApoE –/– mice compared to PFOS. In vitro experiments showed that OBS, at the same exposure concentrations and durations as PFOS (0.1–20 μmol/L, 48 h), more effectively inhibited cell viability of human umbilical vein endothelial cells (HUVECs), caused higher levels of lactate dehydrogenase (LDH) release, and enhanced cell adhesion between HUVECs and monocytes. Both PFOS and OBS were found to activate the NF-κB signaling pathway and upregulate the expression of inflammatory factors. Notably, the use of OBS, but not PFOS, was shown to disrupt cell junctions and increase endothelial permeability by activating the MAPK/ERK signaling pathway. Our findings suggest that OBS may lead to endothelial dysfunction and have a greater impact on AS compared to PFOS, presenting significant health risks in cardiovascular diseases.