MicroRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155

Biros, Erik, Moran, Corey S., Wang, Yutang, Walker, Philip J., Cardinal, John and Golledge, Jonathan (2013) MicroRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155. Clinical Science, Immediate Publication 1-17. doi:10.1042/CS20130599

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Author Biros, Erik
Moran, Corey S.
Wang, Yutang
Walker, Philip J.
Cardinal, John
Golledge, Jonathan
Title MicroRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155
Journal name Clinical Science   Check publisher's open access policy
ISSN 0143-5221
1470-8736
Publication date 2013-11-28
Year available 2013
Sub-type Article (original research)
DOI 10.1042/CS20130599
Open Access Status
Volume Immediate Publication
Start page 1
End page 17
Total pages 17
Place of publication London, United Kingdom
Publisher Portland Press
Language eng
Formatted abstract
Abdominal aortic aneurysm (AAA) is a potentially life threatening late onset degenerative condition. MicroRNAs, the small non-coding RNA molecules that regulate gene expression, have been previously shown to be associated with a broad range of human pathologies, including cardiovascular diseases. The aim of this study was to identify AAA-associated microRNAs potentially contributing to AAA pathology. We analyzed the expression of 124 microRNAs within AAA biopsies and serum of 10 patients undergoing AAA repair, and serum from 10 age- and sex-matched subjects without AAA, using the FlexmiR™ MicroRNA Assay. RNA extracted from the site of main AAA dilatation (AAA body) was compared with that extracted from the macroscopically non-dilated neck of the AAA (AAA neck). Similarly, RNA extracted from the serum of AAA patients (AAA serum) was compared with that extracted from age and sex matched controls (control serum). Real-time quantitative PCR (qRT-PCR), western blot, and histology were performed using an independent set of 6 paired AAA body and neck biopsies to examine the validity of findings. Seven microRNAs were upregulated (>2-fold difference, FDR<0.5) within AAA biopsies, of which miR-155 was the most differentially expressed (11.32-fold, FDR=0.414). This finding was confirmed by qRT-PCR with median relative expression of miR-155 being 3.26 and 0.63 within AAA body and AAA neck biopsies, respectively (P=0.031). Circulating miR-155 was also increased in AAA patients compared to controls with a 2.67-fold upregulation at borderline significance (FDR=0.554). Two immunologically important miR-155 target genes, CTLA4 and SMAD2, were assessed and found to be significantly downregulated within AAA bodies compared to AAA necks (P=0.032 and P=0.026) as determined by qRT-PCR and western blotting, respectively. Histology demonstrated dense accumulation of T-lymphocytes within the adventitial and outer medial layers of AAA body but not neck tissue. This study suggests that miR-155 is overexpressed in AAA with potential implications in the pathogenesis of the condition.
Keyword miRNAs
Transcript expression analysis
Vascular diseases
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published on 28 Nov 2013 as manuscript CS20130599

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
 
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Created: Wed, 11 Dec 2013, 21:32:25 EST by Roheen Gill on behalf of School of Medicine