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<p>Perfluorooctane sulfonic acid (PFOS) is a fluorinated chemical utilized in a variety of industrial and household products. PFOS has been detected in human serum and is associated with multiple human adverse health effects. Epidemiological evidence has linked PFOS exposure to endothelial dysfunction, which is a key contributor to atherosclerosis. However, the underlying mechanisms of PFOS-induced endothelial dysfunction associated atherosclerosis has not been investigated. In the present study, human microvascular endothelial cells (HMEC-1) exposed to PFOS (15&#xa0;μM) for 72&#xa0;h, mimicking long-term exposure. We further employed integrated RNA-sequencing (RNA-seq) and transcriptomic analysis to identify differentially expressed genes (DEGs) for biological alterations: gene ontology (GO), pathway enrichment analysis (KEGG), protein–protein interaction network and modular clustering analysis. Furthermore, the Metascape database was used for disease association, tissue specificity, and transcription factor analysis. Hub genes were verified using atherosclerosis patient data sets from the GEO dataset. Alteration of hub genes in patients was then validated using immunoblotting and ELISA. Our results revealed that PFOS altered amino acid biosynthesis, lipid metabolism and induced the ER-stress response through the HRI/eIF2α/ATF4 pathway, leading to endothelial dysfunction. Interestingly, we found that PFOS induced inflammation by increasing COX-2, ICAM-1 and IL-6 expression through NF-κB and JAK2/STAT3 pathway in endothelial cells. Moreover, up-regulated C/EBPβ and ATF4 were observed in both patients and PFOS-exposed endothelium, which may use as an early biomarker and may have a potential role in PFOS-induced endothelial dysfunction. These findings provide novel insight into the underlying molecular mechanisms of PFOS-induced endothelial dysfunction associated with atherosclerosis.</p>

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Perfluorooctane sulfonic acid: a possible risk factor of endothelial dysfunction based on in silico and in vitro studies

  • 期刊论文

  • 发表日期：

    2025年4月17日

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  • Nutsira Vajeethaveesin,
  • Jantamas Kanitwithayanun,
  • Tawit Suriyo,
  • Suthipong Chujan,
  • Jutamaad Satayavivad

摘要

Perfluorooctane sulfonic acid (PFOS) is a fluorinated chemical utilized in a variety of industrial and household products. PFOS has been detected in human serum and is associated with multiple human adverse health effects. Epidemiological evidence has linked PFOS exposure to endothelial dysfunction, which is a key contributor to atherosclerosis. However, the underlying mechanisms of PFOS-induced endothelial dysfunction associated atherosclerosis has not been investigated. In the present study, human microvascular endothelial cells (HMEC-1) exposed to PFOS (15 μM) for 72 h, mimicking long-term exposure. We further employed integrated RNA-sequencing (RNA-seq) and transcriptomic analysis to identify differentially expressed genes (DEGs) for biological alterations: gene ontology (GO), pathway enrichment analysis (KEGG), protein–protein interaction network and modular clustering analysis. Furthermore, the Metascape database was used for disease association, tissue specificity, and transcription factor analysis. Hub genes were verified using atherosclerosis patient data sets from the GEO dataset. Alteration of hub genes in patients was then validated using immunoblotting and ELISA. Our results revealed that PFOS altered amino acid biosynthesis, lipid metabolism and induced the ER-stress response through the HRI/eIF2α/ATF4 pathway, leading to endothelial dysfunction. Interestingly, we found that PFOS induced inflammation by increasing COX-2, ICAM-1 and IL-6 expression through NF-κB and JAK2/STAT3 pathway in endothelial cells. Moreover, up-regulated C/EBPβ and ATF4 were observed in both patients and PFOS-exposed endothelium, which may use as an early biomarker and may have a potential role in PFOS-induced endothelial dysfunction. These findings provide novel insight into the underlying molecular mechanisms of PFOS-induced endothelial dysfunction associated with atherosclerosis.