GSE4567

Platform: HG-U133_Plus_2

Organism: Homo sapiens

Pdf version of the dendrogram

Set title:

Endothelial cell culture with Chapel Hill Ultrafine particle

Citation:

Karoly ED, Li Z, Dailey LA, Hyseni X et al. Up-regulation of tissue factor in human pulmonary artery endothelial cells after ultrafine particle exposure. Environ Health Perspect 2007 Apr;115(4):535-40.

Set summary:

Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, however, the mechanism remains unknown. In this study, we hypothesized that the ultrafine fraction of ambient pollutant particles would cause endothelial cells dysfunction. We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine Chapel Hill particles (UFP) (100μg/ml) or vehicle for 4h with Affymetrix HG U133 Plus 2.0 chips (N = 4 each). Using an unpaired t-test (p <0.01, 5% false discovery rate) we found 426 unique genes to be differentially expressed with 320 upregulated genes and 106 downregulated genes. Among these genes, we noted upregulation of genes related to coagulation-inflammation circuitry including tissue factor (F3), coagulation factor II receptor-like 2 (F2RL2, PAR3), interleukin (IL)-6 and IL-8. Upregulation of these genes were independently confirmed by RT-PCR and/or protein release. Genes related to the CXC chemokine family that have been implicated in the pathogenesis of vascular disease were upregulated, including MCP-1 (2.60 fold), IL-8 (2.47 fold), CXCL1 (1.41 fold), CXCL2 (1.95 fold), CXCL3 (2.28 fold) and CXCR4 (1.30 fold). In addition, genes related to clotting independent signaling of F3 were also differentially expressed, including FOS, JUN and NFKBIA. Treatment of HPAEC with UFP for 16 hours increased the release of IL6 and IL8 by 1.9-fold and 1.8-fold respectively. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL6 and IL8 release by 30% and 70% respectively. Thus using gene profiling, we uncovered that UFP may induce vascular endothelial cells to express genes related to clotting and angiogenesis. These results provide a novel hypothesis that PM may cause cardiovascular adverse health effects via induction of tissue factor in vascular endothelial cells which then triggers clotting dependent and independent downstream signaling. Keywords: particle treatment


Sample_name Description Type Treatment Dose NP_size
GSM101996 endothelial cell_control_rep1(53) pulmonary artery endothelial cell vehicle - -
GSM101997 endothelial cell_control_rep2(54) pulmonary artery endothelial cell vehicle - -
GSM101998 endothelial cell_control_rep3(55) pulmonary artery endothelial cell vehicle - -
GSM101999 endothelial cell_control_rep4(56) pulmonary artery endothelial cell vehicle - -
GSM102000 endothelial cell_UFP treatment_rep1(57) pulmonary artery endothelial cell ultrafine particle (Chapel Hill) 100µg/ml <0.1µm
GSM102001 endothelial cell_UFP treatment_rep2(58) pulmonary artery endothelial cell ultrafine particle (Chapel Hill) 100µg/ml <0.1µm
GSM102002 endothelial cell_UFP treatment_rep3(59) pulmonary artery endothelial cell ultrafine particle (Chapel Hill) 100µg/ml <0.1µm
GSM102003 endothelial cell_UFP treatment_rep4(60) pulmonary artery endothelial cell ultrafine particle (Chapel Hill) 100µg/ml <0.1µm

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