Integrated Transcriptomic Analysis Identifies Novel Candidate Genes Associated with Calcific Aortic Valve Disease

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Genomics

Background:

• Calcified aortic valve disease (CAVD) is a common condition in older adults, leading to aortic stenosis.
• Current treatments for advanced CAVD involve valve replacement, but effective medications to slow disease progression are unavailable.
• Identifying new biomarkers and therapeutic targets for CAVD is crucial.

Purpose of the Study:

• To comprehensively analyze the transcriptional profile of CAVD using integrated transcriptomic data.
• To identify novel candidate genes and pathways involved in CAVD pathogenesis.
• To explore the potential of identified genes as biomarkers and therapeutic targets.

Main Methods:

• Integrated analysis of multiple transcriptomic datasets.
• Machine learning for feature gene identification.
• Pathway enrichment, protein-protein interaction (PPI) network, and single-cell RNA sequencing (sc-RNA-Seq) analyses.
• Validation using quantitative PCR and Western blot on human tissues.

Main Results:

• Identified 119 CAVD-associated genes, mainly in ossification and extracellular matrix organization.
• Discovered BAMBI, HAND2, and MYOC as significantly downregulated ossification genes in CAVD.
• Observed decreased expression of these genes during VIC osteogenic progression and negative correlation with immune signatures.

Conclusions:

• BAMBI, HAND2, and MYOC are novel candidate genes implicated in CAVD pathogenesis.
• These genes represent potential biomarkers and therapeutic targets for CAVD.
• Findings offer new insights into CAVD mechanisms and potential interventions.