Endothelial transcriptomic changes induced by oxidized low density lipoprotein disclose an up-regulation of Jak–Stat pathway

Oxidized low density lipoproteins (oxLDLs) act as an etiological factor in the development of atherosclerosis by modifying the biological properties of endothelial cells through mechanisms of vascular inflammation. To deepen the oxLDL changes at cellular level, a transcriptomic analysis of human umbilical artery endothelial cells (HUAECs) treated with oxLDL was performed to identify the modified signaling pathways. Total RNA was isolated from HUAECs treated with oxLDL (100 μg/ml). Gene expression analysis was carried out using Affymetrix oligonucleotide microarrays. Biological pathway analysis was performed using Ingenuity Pathway Analysis software. Microarray assay demonstrated that oxLDL strongly affected two metabolic and signaling transduction pathways: the biosynthesis of steroids, via modification of nine genes that act sequentially in this metabolic pathway, and the Jak–Stat signaling pathway acting through STAT1 and STAT2. By means of qPCR, immunoblot, RNA interference and inhibitors we demonstrate that the mechanism used by oxLDL to activate Jak–Stat signaling pathway in artery endothelial cells is mainly mediated by STAT1. These findings provide a new mechanistic framework to better understand the effects that oxLDLs exert in artery endothelial cell gene expression and provide a source of hypothesis to understand the involvement of oxLDL in diseases in which endothelial cells play a key role, such as atherosclerosis.

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