血管生成
激酶插入结构域受体
脐静脉
化学
NFAT公司
全氟辛烷
血管内皮生长因子
血管内皮生长因子A
细胞生物学
内分泌学
癌症研究
生物
生物化学
体外
血管内皮生长因子受体
转录因子
有机化学
基因
钠
磺酸盐
作者
Martin Forsthuber,Raimund Widhalm,Sebastian Granitzer,Andreas Marius Kaiser,Hanns Moshammer,Markus Hengstschläger,Helmut Dolznig,Claudia Gundacker
标识
DOI:10.1016/j.envpol.2021.118543
摘要
Perfluorooctane sulfonic acid (PFOS) is a ubiquitous environmental pollutant. In humans, PFOS exposure has been associated with a number of adverse health outcomes, including reduced birth weight. Whether PFOS is capable of affecting angiogenesis and thus possibly fetal development is unknown. Therefore, we investigated 1) the metabolic activity of PFOS-exposed endothelial cells (human umbilical vein endothelial cells, HUVECs), fibroblasts (normal colon fibroblasts, NCFs), and epithelial cells (human colorectal carcinoma cells, HCT116), 2) PFOS-specific inhibition of vascular endothelial growth factor receptor (VEGFR)2 stimulation in KDR/NFAT-RE HEK293 cells, and 3) the antiangiogenic potential of PFOS in a 3D in vitro angiogenesis model of HUVECs and NCFs. In terms of metabolic activity, endothelial cells (HUVECs) were much more sensitive to PFOS than fibroblasts (NCFs) or epithelial cells (HCT116). VEGFR2 signaling in KDR/NFAT-RE HEK293 cells decreased with increasing PFOS concentrations. In co-culture (angiogenesis assay), PFOS treatment resulted in a dose-dependent reduction in tip and branch formation, tip length (μm), and total structural area (μm2) with stable metabolic activity of HUVECs up to high concentrations. We conclude that PFOS possesses antiangiogenic properties. Inhibition of VEGFR2 signaling indicates a possible mechanism of action that can be linked to an existing Adverse Outcome Pathway (AOP43) containing the AO reduced birth weight. Further studies are needed to confirm PFOS-specific adverse effects on angiogenesis, placental perfusion, and fetal growth.
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