Abstract
Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.
Highlights
Abdominal aortic aneurysms (AAA) are segmental dilatations of the abdominal aorta measuring 50% greater than the proximal normal segment, or >3 cm in maximum diameter [1,2]
Demographical characteristics, clinical parameters and expression data of 34 selected miRNA transcripts and 51 selected genes of AAA group were included to the correlation analysis (Table 4, broaden results are provided in Table S9 and S10)
Examining deregulations in miRNA network and consequential effects on gene expression appears as an interesting research tactics for finding novel biomarkers of AAA [25,26,27]
Summary
Abdominal aortic aneurysms (AAA) are segmental dilatations of the abdominal aorta measuring 50% greater than the proximal normal segment, or >3 cm in maximum diameter [1,2]. Patients with AAA may report nonspecific symptoms like abdominal and back pain; in many cases disease progress is asymptomatic. MiRNA-dependent regulation of gene expression emerged as a new tool providing novel opportunities in diagnosis of AAA. Large studies comparing miRNA and gene expression patterns in patients with AAA and healthy individuals may provide novel biomarkers with good discriminative value improving our diagnostic capability of detecting aneurysm, its rates of progression and complications; their introduction to clinical practice requires further investigations [24,25,26,27]. Differential expression of miRNAs in human AAA cases was reported in abdominal aortic tissue, whole blood, serum and plasma samples, deregulation of miRNA expression in PBMCs (peripheral blood mononuclear cells) was not extensively studied. The study design, methodology, article structure and language have been inspired by our previous studies regarding deregulation of miRNA regulatory network in lower extremities arterial disease [28] and chronic venous disease [29]
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