Transcriptomic changes in Human Umbilical Vein Endothelial Cells (HUVEC) after exposure to Tumor Necrosis Factor-Alpha(TNF-a), AdipoRon, and Sphingosine Kinase Inhibitor (SKI-I)

Endothelial dysfunction is one of the earliest manifestations of atherosclerosis development. Adiponectin, a hormone secreted by adipose tissue with insulin-sensitizing and anti-inflammatory properties, offers protection against atherosclerosis. The pleiotropic effects of adiponectin are thought to be mediated by the ceramidase activity of adiponectin receptors. Adiponectin has been shown to reduce ceramide levels in endothelial cells. Still, the effects of adiponectin on other sphingolipids and endothelial lipid metabolism are not completely elucidated. This study investigated the metabolic and sphingolipid alterations in endothelial cells linked to the protective effects of adiponectin against endothelial dysfunction. Human Umbilical Endothelial Cells (HUVECs) were treated with Tumor Necrosis Factor-alpha (TNF-α) to induce endothelial dysfunction. AdipoRon and SKI-I were used to study the effects of adiponectin and sphingosine kinase inhibition in HUVECs. Metabolic changes and sphingolipid alterations were assessed to understand changes in lipid metabolism, and RNA sequencing was used to quantify the transcriptomics changes. To identify the effects of Tumor Necrosis Factor-Alpha(TNF-a), AdipoRon, and Sphingosine Kinase Inhibitor (SKI-I) on Human Umbilical Vein Endothelial Cells (HUVECs), we treated HUVECs with TNF-a, AdipoRon and SKI-I and cominations of these for 12 hours