Gene expression profiling of peripheral blood mononuclear cells in the setting of peripheral arterial disease

Journal of Clinical Bioinformatics

Iftikhar J Kullo¹  Keyue Ding¹  Aparna Dhar¹  Khader Shameer¹  Rizwan Masud¹ 

[1] Division of Cardiovascular Diseases, Mayo Clinic, Rochester MN 55905, USA

关键词: Biomarkers;    Vascular disease;    Microarray analysis;    Gene expression;    Peripheral arterial disease;   

Others  :  805982
DOI  :  10.1186/2043-9113-2-6

 received in 2011-09-21, accepted in 2012-03-12,  发布年份 2012

【 摘 要 】

Background

Peripheral arterial disease (PAD) is a relatively common manifestation of systemic atherosclerosis that leads to progressive narrowing of the lumen of leg arteries. Circulating monocytes are in contact with the arterial wall and can serve as reporters of vascular pathology in the setting of PAD. We performed gene expression analysis of peripheral blood mononuclear cells (PBMC) in patients with PAD and controls without PAD to identify differentially regulated genes.

Methods

PAD was defined as an ankle brachial index (ABI) ≤0.9 (n = 19) while age and gender matched controls had an ABI > 1.0 (n = 18). Microarray analysis was performed using Affymetrix HG-U133 plus 2.0 gene chips and analyzed using GeneSpring GX 11.0. Gene expression data was normalized using Robust Multichip Analysis (RMA) normalization method, differential expression was defined as a fold change ≥1.5, followed by unpaired Mann-Whitney test (P < 0.05) and correction for multiple testing by Benjamini and Hochberg False Discovery Rate. Meta-analysis of differentially expressed genes was performed using an integrated bioinformatics pipeline with tools for enrichment analysis using Gene Ontology (GO) terms, pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular event enrichment using Reactome annotations and network analysis using Ingenuity Pathway Analysis suite. Extensive biocuration was also performed to understand the functional context of genes.

Results

We identified 87 genes differentially expressed in the setting of PAD; 40 genes were upregulated and 47 genes were downregulated. We employed an integrated bioinformatics pipeline coupled with literature curation to characterize the functional coherence of differentially regulated genes.

Conclusion

Notably, upregulated genes mediate immune response, inflammation, apoptosis, stress response, phosphorylation, hemostasis, platelet activation and platelet aggregation. Downregulated genes included several genes from the zinc finger family that are involved in transcriptional regulation. These results provide insights into molecular mechanisms relevant to the pathophysiology of PAD.

【 授权许可】

   
2012 Masud et al; licensee BioMed Central Ltd.

【 图 表 】

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