Work

Evaluation of the causal effects of PFOS on atherosclerosis and its potential toxicological mechanisms: Integrated Mendelian randomization and network toxicology analysis

Year: 2026

Type: article

Abstract: BACKGROUND: Perfluorooctanesulfonic acid (PFOS) can enter the human body through multiple pathways and accumulate in vivo, but its causal relationship with the occurrence and development of atherosclerosis (AS) and the underlying toxicological mechanisms remain unclear. METHODS: Mendelian randomization (MR) analysis was used to explore the causal relationship between PFOS and AS. By integrating multiple public databases, the potential targets for PFOS-induced AS were obtained. Enrichment analysis was conducted to annotate the functional characteristics of target genes and explore potential biological pathways. The protein-protein interaction (PPI) network was used to further screen the core targets. Single-cell RNA sequencing (scRNA-seq) analysis was employed to explore the expression of the core targets in different cell subsets within atherosclerotic plaques. Molecular docking was used to predict the interaction mode between PFOS and core target proteins. RESULTS: Thirty-eight potential targets of PFOS-induced AS were obtained by integrating multiple public databases. Four core targets, namely CD36, MMP9, PPARG, and PTGS1, were identified via the PPI network. The expression of core target genes in atherosclerotic plaques showed significant cellular heterogeneity. Enrichment analysis indicated that PFOS may promote AS through multiple signaling pathways. The results of molecular docking indicated that PFOS had a high affinity with all the core target proteins. CONCLUSIONS: Combining MR with network toxicology analysis, this study investigates the causal relationship between PFOS and AS as well as the underlying toxicological mechanisms, thereby providing scientific evidence and theoretical support for assessing PFOS-induced cardiovascular toxicity and preventing and treating related diseases.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.119618

Authors: Cong Yan, Ning Fang, Yongtai Gong

Institutions: Harbin Medical University, First Affiliated Hospital of Harbin Medical University

Language: English

Topic: Per- and polyfluoroalkyl substances research

Subfield: Environmental Chemistry

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,650