Source:http://linkedlifedata.com/resource/pubmed/id/19279231
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
|
pubmed:dateCreated |
2009-5-29
|
pubmed:abstractText |
Oxidized low-density lipoprotein (OxLDL) has been implicated as a proatherogenic factor with a pathological role in the induction of endothelial dysfunction. Endothelial cells bind and uptake OxLDL primarily through the scavenger receptor lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1), which is believed to mediate critical effects of OxLDL in endothelial cells. To examine the biological events following LOX-1 activation by OxLDL, we used cDNA microarray analysis to globally analyze gene expression changes induced by OxLDL treatment of human aortic endothelial cell line (HAECT) cells overexpressing LOX-1. Consistent with reported functions of OxLDL, in control HAECT cells, OxLDL elicited gene changes in the oxidative stress pathway and other signaling pathways related to OxLDL. With OxLDL treatment, LOX-1-dependent gene expression changes associated with inflammation, cell adhesion, and signal transduction were observed. The transcripts of a number of cytokines and chemokines were induced, which included interleukin-8, CXCL2, CXCL3, and colony-stimulating factor-3. The secretion of these cytokines was confirmed by enzyme-linked immunosorbent assay analysis. In addition, our data revealed a novel link between LOX-1 and a number of genes, including Delta/notch-like epidermal growth factor repeat containing, stanniocalcin-1, cAMP response element modulator, and dual specificity phosphatase 1. Promoter analysis on the genes that changed as a result of LOX-1 activation by OxLDL allowed us to identify early growth response 1 and cAMP response element-binding protein as potential novel transcription factors that function downstream of LOX-1. Our study has enabled us to elucidate the gene expression changes following OxLDL activation of LOX-1 in endothelial cells and discover novel downstream targets for LOX-1.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/OLR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Scavenger Receptors, Class E,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/oxidized low density lipoprotein
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
0363-6143
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
296
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
C1329-37
|
pubmed:meshHeading |
pubmed-meshheading:19279231-Aorta,
pubmed-meshheading:19279231-Cell Adhesion,
pubmed-meshheading:19279231-Cell Line,
pubmed-meshheading:19279231-Cluster Analysis,
pubmed-meshheading:19279231-Endothelial Cells,
pubmed-meshheading:19279231-Gene Expression Profiling,
pubmed-meshheading:19279231-Gene Expression Regulation,
pubmed-meshheading:19279231-Humans,
pubmed-meshheading:19279231-Inflammation,
pubmed-meshheading:19279231-Lipoproteins, LDL,
pubmed-meshheading:19279231-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:19279231-Scavenger Receptors, Class E,
pubmed-meshheading:19279231-Signal Transduction,
pubmed-meshheading:19279231-Transcription, Genetic,
pubmed-meshheading:19279231-Transcription Factors,
pubmed-meshheading:19279231-Transduction, Genetic
|
pubmed:year |
2009
|
pubmed:articleTitle |
LOX-1-dependent transcriptional regulation in response to oxidized LDL treatment of human aortic endothelial cells.
|
pubmed:affiliation |
Biological Technologies, Wyeth Research, Cambridge, MA 02140, USA.
|
pubmed:publicationType |
Journal Article
|