Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of pig endothelium from multiple sites of coronary and non-coronary arteries

ABSTRACT: This study investigates the role of endothelial cell (EC) gene expression in the focal origin of atherosclerosis. The EC transcriptome was profiled in multiple arterial regions of normal swine. Specifically, small amounts of EC RNA were isolated from 7 athero-susceptible and 6 athero-protected regions. The number of replicates for each site varied between 4 and 8. A total of 98 samples from 76 animals were used. For each sample, linearly amplified RNA (labeled with Cy5) was co-hybridized with pooled arterial reference RNA (labeled with Cy3) onto a custom-printed porcine oligo microarray (70-mers).

ORGANISM(S): Sus scrofa

SUBMITTER: Peter Davies

PROVIDER: E-CBIL-42 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis.

Civelek Mete M Manduchi Elisabetta E Riley Rebecca J RJ Stoeckert Christian J CJ Davies Peter F PF

Circulation research 20090806 5

<h4>Rationale</h4>Endothelial function and dysfunction are central to the focal origin and regional development of atherosclerosis; however, an in vivo endothelial phenotypic footprint of susceptibility to atherosclerosis preceding pathological change remains elusive.<h4>Objective</h4>To conduct a comparative multi-site genomics study of arterial endothelial phenotype in atherosusceptible and atheroprotected regions.<h4>Methods and results</h4>Transcript profiles of freshly isolated endothelial ...[more]

PMID: 19661457

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Project description:Acyl-coA synthases (ACSs) produce fatty acyl-CoAs that are used in metabolic and signaling pathways. Metazoans have a large number of ACS genes with differing expression patterns and substrate preferences, but the physiological roles of most ACS genes are unknown. Here, we focused on the C. elegans acyl CoA synthase, ACS-3, which is known to regulate fat uptake and de novo fat synthesis through the conserved nuclear hormone receptor, nhr-25. We performed microarray analysis of acs-3 mutants to elucidate the acs-3-regulated transcription program. This analysis revealed an enrichment among differentially regulated genes of those involved in lipid metabolism, pathogen and wounding responses, and sterol binding genes, among others. As the immunity genes were the most represented gene class, we performed pathogen sensitivity assays to test the phenotypic consequences of this immune gene regulation. Interestingly, acs-3 mutants were hypersensitive to the fungal pathogen D. coniospora, but only mildly sensitive to the bacterial pathogen P. aeruginosa. acs-3 mutation suppressed nhr-25 mutant sensitivity to P. aeruginosa, yet surprisingly microarray analysis of nhr-25(RNAi) animals revealed significant overlap with the acs-3 mutant transcriptome, with an enrichment of pathogen response genes. The upregulation of pathogen response genes in acs-3(ft5) mutants and following nhr-25 reduction-of-function (rf) does not appear to be due to a constitutive osmotic response or defective cuticle barrier, two potential explanations for the acs-3(ft5) and nhr-25(rf) expression of innate immunity genes in the absence of pathogen exposure. Together, these data indicate that ACS-3 promotes resistance to the fungal pathogen, D. coniospora and regulates innate immunity genes through an unknown mechanism. Potential roles for ACS-3 in innate immunity are discussed. We used two-color expression microarrays to compare the transcriptional profiles in two experimental conditions: 1) comparing wild-type (N2) L4 stage larval worms to acs-3(ft5) L4 larval mutant animals; and 2) animals grown to L4 larval stage on bacteria harboring vectors for either control or nhr-25 RNA-interference (RNAi). L4 stage was determined by morphology of the developing vulva. Three biological replicates were used for each experimental condition. Statistically significant changes in gene expression in each experimental were determined using M-bM-^@M-^\linear models for microarray dataM-bM-^@M-^] (limma).

Dataset Information

Transcription profiling of pig endothelium from multiple sites of coronary and non-coronary arteries

Publications

Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis.

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