In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. suppl_1 ( 2014-05)
Abstract:
Embolism from atherosclerotic plaques in the carotid artery is a major cause of stroke, disability and death. The aim of this project was to explore gene expression signatures and clinical parameters of carotid plaque instability in the Biobank of Karolinska Endarterectomies (BiKE). Whole transcriptome profiling by microarrays was performed on n=127 plaques from n=40 asymptomatic (AS) and n=87 symptomatic (S) patients, and on n=10 normal arteries. After normalization and gender adjustments, differential gene expression was assessed by multiple t-tests with Bonferroni correction. Gene set enrichment and pathway analyses were done using DAVID software. Genes significantly upregulated between S and AS plaques were associated with oxidative stress, immune system activation, exopeptidases, lipoprotein particle clearance and bone resorption, Transcription factors and markers of smooth muscle cells were downregulated in this comparison. When S patients with transitory ischemic attacks and minor stroke were compared with amaurosis fugax , most enriched GO terms were angiogenesis, oxidoreductases and inflammation. Patients on statins showed enrichment of calcification, osteoblast differentiation and negative regulation of angiogenesis. Prolonged immune response, lymphocyte activation and apoptosis were processes ongoing in plaques obtained 〉 1 month compared to 〈 2 weeks after symptoms. Many of the differentially expressed genes exhibited strong positive cross-correlations (Spearman r 〉 0.90, p 〈 10E-30) suggesting that they are simultaneously joined in an expression matrix within the plaques. When these genes were connected into a protein-protein interaction network using Cytoscape, several key nodes were discovered centered around HIF1a, ACTN2, HSPG1, CXCR4, CASP4, HSPA6, PDLIM7, S100A9/10, NOS1 and EGFR. In conclusion, analysis of the largest existing global transcriptome database of carotid atherosclerosis reveals novel genes and pathways related to patient phenotype, confirms the important role of inflammation and lipid metabolism, and highlights the role of repair processes and lymphocyte activation in human atherosclerosis.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.34.suppl_1.52
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2014
detail.hit.zdb_id:
1494427-3
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