Transcriptomic-based toxicological investigations of ethanol to human umbilical vein endothelial cells.

Abstract

Ethanol has a complex effect on the cardiovascular system in humans, but the systemic effects of ethanol to endothelial cells were rarely investigated. In this study, we exposed human umbilical vein endothelial cells (HUVECs) to 5- or 50-mM ethanol and performed transcriptomics to investigate the systemic effects of ethanol. While these concentrations of ethanol did not significantly affect HUVEC viability, 5-mM ethanol significantly upregulated and downregulated 59 and 73 genes, respectively, whereas 50-mM ethanol significantly upregulated and downregulated 50 and 80 genes, respectively. Totally, 37 genes were shared by the two concentrations of ethanol. The most significantly altered gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway after 5-mM ethanol treatment were nucleic acid binding (GO:0003676) and Herpes simplex virus 1 infection (ko05168), respectively, whereas the most significantly altered GO term and KEGG pathway by 50-mM ethanol treatment were aryl sulfotransferase activity (GO:0004062) and chemical carcinogenesis (ko05204). We further verified that ethanol treatment downregulated the mRNA levels of CD38 molecule (CD38), ORAI calcium release-activated calcium modulator 2 (ORAI2), cysteinyl leukotriene receptor 2 (CYSLTR2), key genes involved in calcium signaling pathway (ko04020), as well as integrin subunit alpha 2 (ITGA2), and cAMP responsive element binding protein 3 like 2 (CREB3L2), key genes involved in PI3K-Akt signaling pathway (ko04151). The results from this study suggested that ethanol could induce systemic effects and alter signaling pathways in HUVECs.