Perfluorooctane Sulfonate Induces Dysfunction of Human Umbilical Vein Endothelial Cells via Ferroptosis Pathway

• Published in: Toxics (Basel) Vol. 10; no. 9; p. 503
• Main Authors: Cui, Jiajing, Wang, Pingwei, Yan, Shuqi, Liang, Yujun, Liu, Dongge, Ren, Shuping
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 28.08.2022; MDPI
• Subjects: Antibodies; Apoptosis; Cardiovascular diseases; Cell culture; Cell death; Endothelial cells; endothelial dysfunction; Endothelium; Ferritin; Ferroptosis; Flow cytometry; Fluorocarbons; Glutathione; Glutathione peroxidase; Health aspects; Health risks; Heme; HUVECs; Lipid metabolism; Lipid peroxidation; Lipids; Mitochondria; Morphology; Nitric oxide; Oxidative stress; Oxygenase; Pathogenesis; Perfluorooctane sulfonic acid; Peroxidase; Peroxidation; Persistent organic pollutants; PFOS; Physiological aspects; Pollutants; Proteins; Reactive oxygen species; Reagents; ROS; Signal transduction; Sulfonates; Umbilical arteries; Umbilical cord; Umbilical vein; China; Beijing China; St Louis Missouri; United States > US
• ISSN: 2305-6304; 2305-6304
• DOI: 10.3390/toxics10090503

(1) Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, and it is receiving increasing attention regarding its human health risks due to its extensive use. Endothelial dysfunction is a mark of cardiovascular disease, but the basic mechanism of PFOS-induced endothelial dysfunction is still not fully understood. Ferroptosis is a newly defined regulatory cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although ferroptosis has been shown to be involved in the pathogenesis of cardiovascular diseases, the involvement of ferroptosis in the pathogenesis of endothelial dysfunction caused by PFOS remains unclear. (2) Purpose: To explore the role of ferroptosis in the dysfunction of endothelial cells and underlying mechanisms. (3) Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to PFOS or PFOS and Fer-1. The viability, morphology change under electronic microscope, lipid-reactive oxygen species (lipid-ROS), and production of nitric oxide (NO) were determined. The expression of glutathione peroxidase 4(GPX4), ferritin heavy chain protein 1 (FTH1), heme oxygenase 1 (HO-1) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) were analyzed via Western blot analysis. (4) Results: PFOS was shown to cause a decrease in viability and morphological changes of mitochondria, and well as an increase in lipid droplets. The expression of GPX4, FTH1 and HO-1 was decreased, and that of ACSL4 was increased after exposure to PFOS. In addition to the above-mentioned ferroptosis-related manifestations, there was also a reduction in NO content. (5) Conclusions: PFOS induces ferroptosis by regulating the GPX4 and ACSL4 pathways, which leads to HUVEC dysfunction.