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Published on: July 8, 2020
MicroRNA expression signature in human abdominal aortic aneurysms
Matthew C Pahl1, Kimberly Derr, Gabor Gäbel
1The Sigfried and Janet Weis Center for Research, Geisinger Clinic, 100 North Academy Avenue, Pennsylvania 17822-2610, USA. shkuivaniemi@geisinger.edu
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.
Insights
This study identified differentially expressed microRNAs (miRNAs) in abdominal aortic aneurysm (AAA) tissues. These findings suggest miRNAs are involved in the development of AAA, a condition affecting elderly men.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genetics
Background:
- Abdominal aortic aneurysm (AAA) is a prevalent condition in elderly men, characterized by aortic dilatation, inflammation, and matrix degradation.
- The precise mechanisms underlying AAA formation, progression, and rupture remain incompletely understood.
- MicroRNAs (miRNAs) are regulators of gene expression and may contribute to the differential gene expression observed in AAA.
Purpose of the Study:
- To investigate differences in miRNA expression profiles between AAA and control aortic tissues.
- To identify specific miRNAs and their target genes involved in AAA pathogenesis.
Main Methods:
- Microarray analysis of miRNA expression in 5 AAA and 5 control infrarenal aortic tissues.
- Validation of differentially expressed miRNAs using real-time quantitative RT-PCR (qRT-PCR) on 36 AAA and 7 control tissues.
- Bioinformatic analysis of predicted miRNA target genes using databases and network analysis tools.
Main Results:
- Eight miRNAs exhibited significantly different expression levels between AAA and control tissues (adjusted p < 0.05).
- Five of these miRNAs were validated by qRT-PCR.
- 222 predicted miRNA target genes, known to be differentially expressed in AAA, were identified.
- Bioinformatic analysis indicated involvement of several target genes in apoptosis and T-cell activation.
Conclusions:
- Genome-wide analysis revealed differentially expressed miRNAs in human AAA tissue.
- These findings suggest a significant role for miRNAs in the pathogenesis of abdominal aortic aneurysm.
