Key result
Analysis of single-cell and transcriptome data identified MMP1, MMP9, and ROBO1 as key hub genes in valvular interstitial cells that may facilitate calcified aortic valve disease progression.
Why the study?
Valvular interstitial cells are crucial in developing calcified aortic valve disease, but the key genes involved in their function and underlying mechanisms required clarification.
MMP1, MMP9, and ROBO1 are identified as key hub genes in valvular interstitial cells that may drive the progression of calcified aortic valve disease through inflammation and lipid metabolism pathways.
Highlights candidate genes in CAVD; leaves open mechanistic roles and clinical utility pending validation.
Objective Valvular interstitial cells (VICs) are crucial in developing calcified aortic valve disease (CAVD). This investigation integrated single-cell sequencing and transcriptome data analysis to identify key genes involved in VIC function in CAVD and delineate underlying mechanisms. Methods Differentially expressed genes (DEGs) were identified from the GSE51472 and GSE235995 datasets. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were employed to uncover potential functional genes and signaling pathways linked to CAVD. Data from the GSE12644 dataset was employed for external validation of the DEGs obtained. Subcellular population functional annotation along with pseudo-temporal trajectory analysis was utilized to elucidate the roles of DEGs and single-cell subpopulations in CAVD. Results Transcriptome data analysis identified 205 DEGs associated with CAVD, comprising 60 up-regulated and 145 down-regulated genes. Single-cell sequencing demonstrated that VICs were closely linked to the progression of CAVD, with patients exhibiting an increased population of VICs characterized by 437 up-regulated and 1843 down-regulated genes. Pseudo-temporal trajectory analysis revealed inconsistent differentiation functions of VICs in the context of CAVD, particularly concerning inflammation and lipid metabolism pathways. An intersectional analysis combining single-cell and transcriptome data identified 22 DEGs, comprising 2 up-regulated and 20 down-regulated genes. Protein-protein interaction (PPI) analysis revealed three hub genes: MMP1, MMP9, and ROBO1, and their differential expression was further validated by the external GSE12644 dataset. Conclusion Disease-associated VICs are linked to inflammation and lipid metabolic processes. VICs may facilitate the progression of CAVD by modulating the expression levels of MMP1 and MMP9, as well as ROBO1 genes, which ultimately leads to altered cellular functions promoting CAVD progression.
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Wang et al. (2025) studied Calcified aortic valve disease (CAVD). Valvular interstitial cells (VICs) gene expression was evaluated on Differentially expressed genes (DEGs) and hub genes associated with CAVD. Analysis of single-cell and transcriptome data identified MMP1, MMP9, and ROBO1 as key hub genes in valvular interstitial cells that may facilitate calcified aortic valve disease progression.
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