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Series GSE29903 Query DataSets for GSE29903
Status Public on Jun 13, 2011
Title Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Oxidized phospholipids are thought to promote atherogenesis by stimulating endothelial cells (ECs) to produce inflammatory cytokines, such as IL-8. In studies with mouse models, we previously demonstrated that genetic variation in inflammatory responses of endothelial cells to oxidized lipids contributes importantly to atherosclerosis susceptibility. We now show that similar variations occur in cultured aortic ECs derived from multiple heart transplant donors. These variations were stably maintained between passages and, thus, reflect either genetic or epigenetic regulatory differences. Expression array analysis of aortic EC cultures derived from 12 individuals revealed that >1,000 genes were regulated by oxidized phospholipids. We have used the observed variations in the sampled population to construct a gene coexpression network comprised of 15 modules of highly connected genes. We show that several identified modules are significantly enriched in genes for known pathways and confirm a module enriched for unfolded protein response (UPR) genes using siRNA and the UPR inducer tunicamycin. On the basis of the constructed network, we predicted that a gene of unknown function (MGC4504) present in the UPR module is a target for UPR transcriptional activator ATF4. Our data also indicate that IL-8 is present in the UPR module and is regulated, in part, by the UPR. We validate these by using siRNA. In conclusion, we show that interindividual variability can be used to group genes into pathways and predict gene-gene regulatory relationships, thus identifying targets potentially involved in susceptibility to common diseases such as atherosclerosis.
 
Overall design Twelve individual HAEC lines were treated in duplicate (in 35-mm dishes) for 4 h in media containing PAPC (40 μg/ml) or oxidized PAPC (OxPAPC) at 20 ug/ml or 40 μg/ml. Cytoplasmic RNA was isolated by using an RNAeasy kit (Qiagen) and analyzed on an Agilent 2100 Bioanalyzer (Agilent, Palo Alto, CA) to assess RNA integrity. Double-stranded cDNAs were synthesized from total RNA by using the cDNA Synthesis System (Invitrogen, Carlsbad, CA). Biotin-labeled cRNA was generated and used to probe Affymetrix (Santa Clara, CA) Human Genome U133 Plus 2.0 arrays according to the manufacturer’s recommendations (Affymetrix). The Microarray Suite 5.0 software (Affymetrix) was used to analyze image data and make the absolute call for each measurement. The array data were normalized with the median invariant method (31).
 
Contributor(s) Zhang B, Gargalovic P
Citation(s) 16912112
Submission date Jun 12, 2011
Last update date Mar 25, 2019
Contact name Juyong Brian Kim
E-mail(s) jkim@mednet.ucla.edu
Phone 310-825-1595
Fax 310-794-7345
Organization name UCLA School of Medicine
Department Department of Medicine
Lab Lusis Lab
Street address 675 Charles Young Dr.
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (72)
GSM740397 D1C0A_
GSM740398 D1C0B_
GSM740399 D1C20AL
Relations
BioProject PRJNA140811

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE29903_RAW.tar 42.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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