Abstract
BackgroundAbdominal 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.MethodsTo 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®.ResultsA 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.ConclusionsOur genome-wide approach revealed several differentially expressed miRNAs in human AAA tissue suggesting that miRNAs play a role in AAA pathogenesis.
Highlights
Abdominal aortic aneurysm (AAA) is a dilatation of the aorta affecting most frequently elderly men
MicroRNAs are a class of small non-coding RNAs, whose primary function is the post-transcriptional regulation of gene expression. miRNAs are incorporated into the RNA induced silencing complex (RISC) and preferentially bind to the 3’ untranslated region (3’UTR) of target mRNA
The expression levels of the eight miRNAs identified in the microarray study were initially validated using individual real-time quantitative RT-PCR (qRT-PCR) assays and a new set of twelve AAA and seven control aortic tissue samples (Table 1 and Additional file 1: Table S1)
Summary
Abdominal aortic aneurysm (AAA) is a dilatation of the aorta affecting most frequently elderly men. 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. Abdominal aortic aneurysm (AAA) is a dilatation of the aorta (>3 cm) that occurs below the renal arteries [1]. The most of genes with differences in the levels of expression in AAA compared to abdominal aortic tissues from ageand sex-matched controls [9]. MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose primary function is the post-transcriptional regulation of gene expression. Recent studies have demonstrated that miRNAs play roles in several cardiovascular diseases [13]
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