title: Endothelial transcriptomic changes induced by oxidized low density lipoprotein disclose an up-regulation of Jak-Stat pathway.
abstract: 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.
authors.affiliation: Research Foundation, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Laguna-Fernández
authors.affiliation: Research Foundation, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, Spain; Department of Physiology, University of Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Novella
authors.affiliation: Research Foundation, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueno-Betí
authors.affiliation: Cardiovascular and Genetic Epidemiology Research Group (ULEC-EGEC), IMIM, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Marrugat
authors.affiliation: Research Foundation, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario de Valencia, Spain; Department of Physiology, University of Valencia, Spain. Electronic address: carlos.hermenegildo@uv.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hermenegildo
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D053263:Gene Regulatory Networks; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects*; D014162:Transfection
chemical_list: D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; C099252:oxidized low density lipoprotein; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Atherosclerosis; Cell signaling; Endothelial cells; Gene expression; Oxidized low density lipoproteins