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.
Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids.
Cell line, Subject
View SamplesGene expression profiling was carried out on peripheral blood mononuclear cells from 45 adult females. The primary research question is whether leukocyte gene expression differs in individuals with varying levels of estrogen signaling.
No associated publication
No sample metadata fields
View SamplesGene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from renal cell carcinoma patients. The primary research question is whether gene expression differs as a function of patient's level of depression as measured by CESD score > 16.
Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.
Specimen part, Disease
View SamplesGene expression profiling was carried out on peripheral blood CD2+ leukocytes from 29 children with asthma. The primary research question is whether gene expression differs in individuals from high socioeconomic status environments vs low socioeconomic status environments.
Genome-wide transcriptional profiling linked to social class in asthma.
No sample metadata fields
View SamplesAnalysis of the effect of a bacterial quorum sensing molecule on in-vitro culture of human endothelial cells at gene expression levels.
No associated publication
Cell line, Subject
View SamplesGene expression profiling was carried out on peripheral blood CD14+ leukocytes from 21 stressed caregivers and controls (all adult). The primary research question is whether gene expression differs in individuals from high stress vs low stress environments.
A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-kappaB signaling.
No sample metadata fields
View SamplesGene expression profiling was carried out on peripheral blood leukocytes from 14 healthy older adults. The primary research question is whether gene expression differs in individuals experiencing chronically high levels of social isolation (by UCLA Loneliness Scale) vs chronically low levels of social isolation.
Social regulation of gene expression in human leukocytes.
No sample metadata fields
View SamplesGene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 4 mo old rhesus macaques subject to maternal rearing, peer rearing, or surrogate peer rearing. The primary research question is whether gene expression differs as a function of early rearing conditions.
Transcriptional modulation of the developing immune system by early life social adversity.
Age
View SamplesGene expression profiling was carried out on primary ovarian carcinomas from 10 patients. The primary research question is whether gene expression differs in tissues from individuals with high vs low symptoms of psychological depression.
Depression, social support, and beta-adrenergic transcription control in human ovarian cancer.
No sample metadata fields
View SamplesGene expression profiling was carried out on splenocyte mRNA samples collected from 6 animals subject to repeated social threat and 6 animals subject to non-threatening control conditions (pooled into 3 groups of 2). The primary research question is whether gene expression differs in CD11b+ splenocytes from animals exposed to social threat vs non-threatening control conditions.
No associated publication
Specimen part
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