Abstract
The molecular mechanisms underlying thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) are incompletely characterized. MicroRNAs (miRNAs) may play a major role in the different pathogenesis of aortopathy. We sought to employ next-generation sequencing to analyze the entire miRNome in TAA tissue from patients with BAV and tricuspid aortic valve (TAV). In the discovery stage, small RNA sequencing was performed using the Illumina MiSeq platform in 13 TAA tissue samples (seven patients with BAV and six with TAV). Gene ontology (GO) and KEGG pathway analysis were used to identify key pathways and biological functions. Validation analysis was performed by qRT-PCR in an independent cohort of 30 patients with BAV (26 males; 59.5 ± 12 years) and 30 patients with TAV (16 males; 68.5 ± 9.5 years). Bioinformatic analysis identified a total of 489 known mature miRNAs and five novel miRNAs. Compared to TAV samples, 12 known miRNAs were found to be differentially expressed in BAV, including two up-regulated and 10 down-regulated (FDR-adjusted p-value ≤ 0.05 and fold change ≥ 1.5). GO and KEGG pathway enrichment analysis (FDR-adjusted p-value < 0.05) identified different target genes and pathways linked to BAV and aneurysm formation, including Hippo signaling pathway, ErbB signaling, TGF-beta signaling and focal adhesion. Validation analysis of selected miRNAs confirmed the significant down-regulation of miR-424-3p (p = 0.01) and miR-3688-3p (p = 0.03) in BAV patients as compared to TAV patients. Our study provided the first in-depth screening of the whole miRNome in TAA specimens and identified specific dysregulated miRNAs in BAV patients.
Highlights
Dilatation of the aortic root and ascending aorta is frequently present in patients with bicuspid aortic valve (BAV) and can lead to complications, including aneurysm formation and aortic dissection [1]
Aortic diameter is currently the major clinical risk criterion used in combination with other potential risk factors to guide elective surgical repair of ascending aortic aneurysms in BAV patients [2]
The current study has described the entire miRNome of BAV and tricuspid aortic valve (TAV) patients
Summary
Dilatation of the aortic root and ascending aorta is frequently present in patients with bicuspid aortic valve (BAV) and can lead to complications, including aneurysm formation and aortic dissection [1].Aortic diameter is currently the major clinical risk criterion used in combination with other potential risk factors (e.g., family history of dissection, presence of coarctation, root phenotype) to guide elective surgical repair of ascending aortic aneurysms in BAV patients [2].the size criterion is an imperfect predictor of aortic dissection or rupture in many patients who suffer aortic complications at smaller diameters [3].As a consequence, additional predictors (e.g., imaging, genetic or biological markers) are needed to identify individualized therapeutic and surgical strategies [4]. Aortic diameter is currently the major clinical risk criterion used in combination with other potential risk factors (e.g., family history of dissection, presence of coarctation, root phenotype) to guide elective surgical repair of ascending aortic aneurysms in BAV patients [2]. MicroRNAs (miRNAs) are short non-coding RNAs (~22 nucleotides) that negatively modulate gene expression at the post-transcriptional level through binding to the 3 UTR of their target mRNA [7]. Based on their long half-life in blood and selective expression in certain tissues, miRNAs can be key modulators in the development of aortic aneurysm as well as potential circulating biomarkers in the progression of BAV aortopathy [4,8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
