Effect of Oxidized Low-Density Lipoprotein on Differential Gene Expression in Primary Human Endothelial Cells

Abstract

Oxidative modification of low-density lipoprotein (LDL) plays an important role in the initiation and progression of atherosclerosis. It has been proposed that the biological action of oxidized LDL (ox-LDL) may be partially attributed to its effect on a shift of the pattern of gene expression in endothelial cells. To examine the transcriptional response to ox-LDL, we applied cDNA array technology to cultured primary human endothelial cells challenged with oxidized human LDL. A twofold or greater difference in the expression of a particular gene was considered a significant difference in transcript abundance. Seventy-eight of the 588 genes analyzed were differentially expressed in response to the treatment. Ox-LDL significantly affected the expression of genes encoding for transcription factors, cell receptors, growth factors, adhesion molecules, extracellular matrix proteins, and enzymes involved in cholesterol metabolism. The alteration of the expression pattern of several genes was substantiated post hoc using RT-PCR. The experimental strategy identified several novel ox-LDL-sensitive genes associated with a "response to injury" providing a conceptual background to be utilized for future studies addressing the molecular basis of the early stages of atherogenesis.

Daily Quercetin Supplementation Dose-Dependently Increases Plasma Quercetin Concentrations in Healthy Humans

“…Zern et al (43) recently found that dietary supplementation with grape powder containing quercetin in preand postmenopausal women significantly decreased oxidative stress as measured by F2-isoprostanes and also decreased the levels of plasma TNFa. As previously demonstrated, TNFa and other cytokines and growth factors are stimulated by reactive oxygen species and ox-LDL (44,45). Our finding that quercetin supplementation did not decrease the concentrations of the proinflammatory cytokine TNFa might be explained by a general lack of quercetin to reduce TNFa under the conditions prevailing in the present study or could be due to the lack of oxidative stress in our study subjects.…”

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

“…The source of lipids or lipoproteins, concentrations, time of exposure and the origin of the endothelial cells vary substantially among the studies. In agreement with our results, all the studies in which oxLDL were used to stimulate the cells show an enrichment in cell communication and cholesterol metabolism processes [36][37][38][39]. In addition, the response to stress process was a common trait with the studies that used oxPAPC [40,41].…”

Modulation of Growth Factor Gene Expression in Vascular Cells by Oxidative Stress

“…These growth factors are produced by a variety of cells and are mitogenic for fibroblasts, smooth muscle cells (SMCs), and numerous other cell types, mainly of mesenchymal origin. Microarray analysis of HUVECs revealed that PDGF-A as well as PDGF-Rα are highly induced by oxLDL after 6 h of treatment (Virgili et al 2003). We have shown PDGF-A expression is induced by oxLDL occurred at the level of transcription (M.E., L.M.K., unpublished data).…”

“…Recent microarray analysis of HUVEC treated by oxLDL for 6 h revealed that VEGF as well as VEGF 155 R (neuropilin-1) and VEGFR2 (Flk1) are induced in these cells. Thus, oxLDL may induce VEGF signaling by increasing both the ligand and its receptors (Virgili et al 2003).…”