STANDARD_NAME	GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_PURPLE_DN
SYSTEMATIC_NAME	M27964
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_PURPLE_DN
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes from the purple module which are dn-regulated in HAEC cells (primary aortic endothelium) after exposure to the oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycerophosphorylcholine (oxPAPC).
DESCRIPTION_FULL	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.
PMID	16912112
GEOID	
AUTHORS	Gargalovic PS,Imura M,Zhang B,Gharavi NM,Clark MJ,Pagnon J,Yang WP,He A,Truong A,Patel S,Nelson SF,Horvath S,Berliner JA,Kirchgessner TG,Lusis AJ
CONTRIBUTOR	Anthony Castanza
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S: module=purple & fold change < 0.667
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	1556336_at,1556352_at,1560031_at,1564733_at,1570351_at,209721_s_at,215447_at,215811_at,220866_at,227074_at,227517_s_at,230791_at,232333_at,232375_at,232500_at,232544_at,232882_at,232889_at,233123_at,235085_at,235444_at,235926_at,236237_at,236432_at,236545_at,237157_at,237895_at,238608_at,239257_at,239448_at,239576_at,239723_at,240263_at,240690_at,241473_at,241906_at,242343_x_at,242652_at,242859_at,243933_at,244420_at
GENE_SYMBOLS	RBMX,,,,ADAMTS6,IFFO1,,,ADAMTS6,CCDC18-AS1,GAS5,,,STAT1,RALGAPA2,,,,,PRAG1,FOXP1,ANAPC5,,,,,,LAMB1,MOV10L1,,MTUS1,,,,,,,,,,
FOUNDER_NAMES