Biological effects of chronic and acute exposure of human endothelial cell line EA.hy926 to bisphenol A: New tricks from an old dog.

Abstract:

:Although epidemiological and animal studies suggest a possible correlation between bisphenol A (BPA) exposure and atherosclerosis, very few in vitro mechanistic and functional studies regarding the effect of BPA on vascular cells have been conducted. Here, we applied a "real-life" exposure scenario by continuously exposing human endothelial cell (EC) line EA.hy926 to environmentally relevant concentrations of BPA (10-9, 10-8, and 10-7 M) during 14 weeks. We also exposed EA.hy926 cells to higher concentrations of BPA (10-7, 10-6, and 10-5 M) for up to 48 h to gain mechanistic insight into the BPA's action in ECs. Chronic exposure to BPA produced some unexpected effects in EA.hy926 cells including a transient decrease in the adhesion of monocytes to the EC monolayer and decrease in the expression of cellular adhesion molecules, improvement in endothelial barrier function and elevated expression of tight junction proteins occludin and zonula occludens-1 (ZO-1), increased adhesion of ECs, and increased nitric oxide (NO) production. Some of these effects, such as diminished adhesion of monocytes to the EC monolayer and elevated NO production have also been replicated during acute exposure experiments. Using Western blotting and specific pharmacological inhibitors in the acute study, we have shown that direct BPA's action in EA.hy926 cells involves activation of estrogen receptor (ER), phosphorylation of protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS)-mediated production of NO. Collectively, these data indicate that BPA induces functional and molecular changes in EA.hy926 cells associated with the promotion of endothelial integrity through activation of the ER/Akt/eNOS pathway.

journal_name

Chemosphere

journal_title

Chemosphere

authors

Kokai D,Stanic B,Samardzija Nenadov D,Pogrmic-Majkic K,Tesic B,Fa S,Andric N

doi

10.1016/j.chemosphere.2020.127159

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

127159

eissn

0045-6535

issn

1879-1298

pii

S0045-6535(20)31352-7

journal_volume

256

pub_type

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