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Open Access Highly Accessed Research article

MicroRNA expression signature in human abdominal aortic aneurysms

Matthew C Pahl12, Kimberly Derr1, Gabor Gäbel3, Irene Hinterseher35, James R Elmore4, Charles M Schworer1, Thomas C Peeler2, David P Franklin4, John L Gray4, David J Carey1, Gerard Tromp1 and Helena Kuivaniemi1*

Author affiliations

1 The Sigfried and Janet Weis Center for Research, Geisinger Clinic, 100 North Academy Avenue, Pennsylvania, 17822-2610, USA

2 Department of Biology, Susquehanna University, Selinsgrove, PA, USA

3 Department of Visceral, Thoracic and Vascular Surgery, Technical University of Dresden, Dresden, Germany

4 Department of Vascular and Endovascular Surgery, Geisinger Clinic, Danville, PA, USA

5 Department of General, Visceral, Vascular and Thoracic Surgery, Charité Universitätsmedizin, Charité Campus Mitte, Berlin, Germany

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Citation and License

BMC Medical Genomics 2012, 5:25  doi:10.1186/1755-8794-5-25

Published: 15 June 2012

Abstract

Background

Abdominal aortic aneurysm (AAA) is a dilatation of the aorta affecting most frequently elderly men. Histologically AAAs are characterized by inflammation, vascular smooth muscle cell apoptosis, and extracellular matrix degradation. The mechanisms of AAA formation, progression, and rupture are currently poorly understood. A previous mRNA expression study revealed a large number of differentially expressed genes between AAA and non-aneurysmal control aortas. MicroRNAs (miRNAs), small non-coding RNAs that are post-transcriptional regulators of gene expression, could provide a mechanism for the differential expression of genes in AAA.

Methods

To determine differences in miRNA levels between AAA (n = 5) and control (n = 5) infrarenal aortic tissues, a microarray study was carried out. Results were adjusted using Benjamini-Hochberg correction (adjusted p < 0.05). Real-time quantitative RT-PCR (qRT-PCR) assays with an independent set of 36 AAA and seven control tissues were used for validation. Potential gene targets were retrieved from miRNA target prediction databases Pictar, TargetScan, and MiRTarget2. Networks from the target gene set were generated and examined using the network analysis programs, CytoScape® and Ingenuity Pathway Core Analysis®.

Results

A microarray study identified eight miRNAs with significantly different expression levels between AAA and controls (adjusted p < 0.05). Real-time qRT-PCR assays validated the findings for five of the eight miRNAs. A total of 222 predicted miRNA target genes known to be differentially expressed in AAA based on a prior mRNA microarray study were identified. Bioinformatic analyses revealed that several target genes are involved in apoptosis and activation of T cells.

Conclusions

Our genome-wide approach revealed several differentially expressed miRNAs in human AAA tissue suggesting that miRNAs play a role in AAA pathogenesis.

Keywords:
Apoptosis; Microarray analysis; Vascular biology; miRNA-mRNA analysis; Network analysis