STANDARD_NAME GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP SYSTEMATIC_NAME M11672 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Genes from the blue module which are up-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 Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1S: module=blue & fold change >= 1.5 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1553713_a_at,1554333_at,1554334_a_at,1554462_a_at,1554980_a_at,1556194_a_at,1556228_a_at,1559352_a_at,1568768_s_at,1570253_a_at,200664_s_at,200666_s_at,200799_at,200800_s_at,200881_s_at,200924_s_at,201491_at,201695_s_at,201844_s_at,201845_s_at,201846_s_at,202146_at,202147_s_at,202241_at,202581_at,202672_s_at,202693_s_at,202763_at,202842_s_at,202843_at,202859_x_at,202928_s_at,203068_at,203378_at,203574_at,203751_x_at,203821_at,203957_at,204182_s_at,204194_at,204210_s_at,204285_s_at,204286_s_at,204363_at,204420_at,204668_at,204926_at,205178_s_at,205205_at,205543_at,205923_at,206175_x_at,206907_at,206976_s_at,207000_s_at,207850_at,208370_s_at,208394_x_at,208707_at,208744_x_at,208763_s_at,209015_s_at,209020_at,209211_at,209212_s_at,209383_at,209681_at,210426_x_at,210479_s_at,210511_s_at,211506_s_at,211924_s_at,212666_at,212722_s_at,212723_at,212780_at,212923_s_at,213124_at,213310_at,213330_s_at,213418_at,213750_at,214326_x_at,214430_at,214696_at,214714_at,214748_at,214751_at,217168_s_at,217672_x_at,217911_s_at,218474_s_at,218562_s_at,218566_s_at,218647_s_at,218954_s_at,218955_at,219496_at,219966_x_at,220018_at,220330_s_at,220346_at,221667_s_at,221954_at,222706_at,222852_at,223145_s_at,223195_s_at,223196_s_at,223297_at,223309_x_at,223394_at,224466_s_at,224480_s_at,224761_at,224783_at,224785_at,224829_at,224831_at,225018_at,225061_at,225142_at,225183_at,225252_at,225256_at,225378_at,225434_at,225550_at,225878_at,226003_at,226045_at,226206_at,226275_at,226360_at,226534_at,226650_at,226732_at,226968_at,226989_at,227034_at,227140_at,227292_at,227304_at,227443_at,227693_at,228081_at,228177_at,228328_at,228442_at,228445_at,228655_at,228846_at,228914_at,228928_x_at,229011_at,229318_at,229347_at,229504_at,229564_at,229926_at,230048_at,230063_at,230082_at,230102_at,230296_at,230511_at,230561_s_at,230721_at,231292_at,231899_at,233186_s_at,233898_s_at,233952_s_at,234491_s_at,235573_at,235727_at,237016_at,238087_at,239835_at,239845_at,241262_at,32541_at,38037_at GENE_SYMBOLS RHEBL1,DNAJA4,DNAJA4,DNAJB9,ATF3,HSPA4L,VCPIP1,MILIP,,RHEBL1,DNAJB1,DNAJB1,HSPA1A,HSPA1A,DNAJA1,SLC3A2,AHSA1,PNP,RYBP,RYBP,RYBP,IFRD1,IFRD1,TRIB1,HSPA1B,ATF3,STK17A,CASP3,DNAJB9,DNAJB9,CXCL8,PHF1,KLHL21,PCF11,NFIL3,JUND,HBEGF,E2F6,ZBTB43,BACH1,PCYT1A,PMAIP1,PMAIP1,F3,FOSL1,RNF24,INHBA,RBBP6,RELB,HSPA4L,RELN,ZNF222,TNFSF9,HSPH1,PPP3CC,CXCL3,RCAN1,ESM1,EIF5,HSPH1,TSC22D3,DNAJB6,OSER1,KLF5,KLF5,DDIT3,SLC19A2,RORA,RORA,INHBA,CXCL8,PLAUR,SMURF1,JMJD6,JMJD6,SOS1,PXDC1,ZNF473,AGO2,STIP1,HSPA6,RSL1D1,JUND,GLA,MIR22HG,ZNF394,N4BP2L2,ZNF468,HERPUD1,,BAG3,KCTD5,MACO1,CHORDC1,YRDC,BRF2,BRF2,SOWAHC,BANP,CBLL1,SAMSN1,MTHFD2L,HSPB8,OSER1,CWC25,C10orf88,AKIRIN2,SESN2,SESN2,AMMECR1L,PNPLA8,SERTAD1,MAFG,GPAT3,GNA13,UBALD2,UBALD2,CPEB4,CPEB4,SPIRE1,DNAJA4,KDM7A,HAPSTR1,SRXN1,,VPS37A,DEDD2,CNST,KIF1B,KIF21A,FRS2,MAFK,MXD1,ZNRF3,KITLG,ZFAND2A,RBM33,KIF1B,RGMB,SOWAHC,INHBA,SPINDOC,SMCR8,LURAP1L,WDR20,CCNG2,CREBBP,KLHL28,NFATC2,AIFM2,,MXD1,,BANP,EMP1,NUTM2B-AS1,MIR4458HG,RAB23,RRP7A,MIR3682,IFRD1,ZNF264,UBE2FP1,,MOSMO,CREM,KANSL1L,MOSMO,EID3,ZC3H12C,BANP,FGFR1OP2,ZBTB21,SAV1,HSPH1,KLHL28,TMEM217,RTCA,KBTBD8,MAP1LC3B,,PPP3CC,HBEGF FOUNDER_NAMES