miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing

Area of Science:

• Cardiovascular Biology
• Molecular Genetics
• Aortic Disease Research

Background:

• Thoracic aortic aneurysm (TAA) pathogenesis in bicuspid aortic valve (BAV) patients is not fully understood.
• MicroRNAs (miRNAs) are potential key regulators in the development of aortopathy.

Purpose of the Study:

• To comprehensively analyze the miRNome in TAA tissues from patients with BAV and tricuspid aortic valve (TAV).
• To identify differentially expressed miRNAs and associated biological pathways in BAV-related TAA.

Main Methods:

• Next-generation sequencing (small RNA sequencing) of TAA tissue from BAV and TAV patients.
• Bioinformatic analysis including Gene Ontology (GO) and KEGG pathway enrichment.
• Quantitative reverse transcription PCR (qRT-PCR) for miRNA validation.

Main Results:

• Discovery identified 489 known and 5 novel miRNAs; 12 known miRNAs were differentially expressed between BAV and TAV TAA tissues.
• Enrichment analysis revealed involvement of pathways such as Hippo signaling, ErbB signaling, TGF-beta signaling, and focal adhesion.
• Validation confirmed significant down-regulation of miR-424-3p and miR-3688-3p in BAV patients compared to TAV patients.

Conclusions:

• This study presents the first in-depth miRNome screening of TAA specimens.
• Specific miRNAs, including miR-424-3p and miR-3688-3p, are dysregulated in BAV-associated TAA, suggesting their role in disease pathogenesis.