Ethanol impairs expression of estrogen receptors and increases ICAM-1 and galectin-3 in human umbilical vein and cerebral microvascular endothelial cells

Background: Endothelial cells play a pivotal role in maintaining vascular homeostasis and endothelial dysfunction (ED) is an underlying mechanism of cardiovascular disease. Estrogen deficiency is one of the causes of ED that precedes the changes in vasomotor tone, inflammation and arterial stiffness, leading to vascular structural changes and increased blood pressure. Aim: To determine the effects of ethanol (EtOH) on the expression of estrogen receptors (ERs) and inflammatory markers (ICAM-1, galectin-3) using two different types of endothelial cells: human umbilical vein (HUVEC), as a model of large vessel endothelial cells, and cerebral microvascular endothelial cells (hCMEC), which are associated with the blood-brain barrier. Methods: Cells were treated with EtOH and ED and were then evaluated for the expression of ERs (ERα, ERβ, G protein coupled ER (GpER)), as well as for the regulation of ICAM-1, galectin-3, and the phosphorylation of IκBα using Western blot assay. Results: Exposure to EtOH decreased the expression of ERα and GpER, but did not change ERβ (ERα was not detected in the HUVEC line used in this study). In terms of inflammatory factors, EtOH increased ICAM-1 and galectin-3 in both cell lines and activated p-IκBα in hCMEC. Conclusions: These findings suggest that alcohol accelerates ED by decreasing estrogenic effects and increasing inflammatory response in both the systemic and cerebral vasculature.1 page(s