Cadmium exposure alters steroid receptors and proinflammatory cytokine levels in endothelial cells in vitro: a potential mechanism of endocrine disruptor atherogenic effect
Cadmium (Cd) is a widespread environmental pollutant that causes alterations in human health acting as endocrine disruptor. Recent data suggest that cardiovascular system might be a contamination target tissue, since Cd is found in atheromatic plaques. Thus, the purpose of this study was to evaluate the consequence of Cd exposure of endothelial cells in vitro to evaluate detrimental effect in vascular system by a potential sex-steroid hormone receptor-dependent mechanism(s).
To this aim, Human Umbilical Vein Endothelial Cells (HUVECs) were cultured and exposed to several concentrations of cadmium chloride (CdCl2) for different interval times.
CdCl2 exposure of HUVECs induced a significant increase of ERβ and Cyp19a1 at both mRNA and protein levels, while a drastic dose-dependent decrease of AR expression level was observed after 24 h of exposure. On the contrary, an increase of PhARser308 as well as a reduction of PhGSK-3βser9 and PhAKTser473 was detected after 1 h treatment. This effect was consistently reduced by GSK inhibition. Furthermore, CdCl2 abolished DHT-induced cell proliferation in HUVECs suggesting an antagonist-like effect of Cd on AR-mediated signaling. Remarkable, after 6 h CdCl2—treatment, a relevant increase in TNF-α, IL-6 and IL-8 mRNA was observed and this effect was blocked by the presence of an ERβ-selective antagonist. Moreover, Cd-induced TxR1 overexpression, likely, correlated with the activation of p38 MAPK/NF-κB pathway.
In conclusion, our study demonstrates for the first time that Cd alters sex-steroid hormone receptors level and activity likely affecting intracellular signaling linked to a proinflammatory state in endothelial cells. This alteration might possibly lead to endothelial cell injury and vascular dysfunction and could be a mechanism of gender-specific atherogenic damages induced by endocrine disruptors and, thus, induce atherogenic events with increased risk of cardiovascular diseases in individuals exposed to this endocrine disruptor.
KeywordsCadmium Endocrine disruptor Androgen receptor Estrogen receptor and cardiovascular diseases Cytokines Gender
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
No informed consent was needed since no human studies are included in the manuscript.
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