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Updated: Nov 4, 2025
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Predicting the Key Genes Involved in Aortic Valve Calcification Through Integrated Bioinformatics Analysis
Dinghui Wang1, Tianhua Xiong1, Wenlong Yu1
1Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Insights
Calcific aortic valve disease (CAVD) lacks effective treatments. This study identifies key chemokines and immune cells, like macrophages and B cells, involved in CAVD progression, offering potential therapeutic targets.
Area of Science:
- Cardiovascular Research
- Immunology
- Bioinformatics
Background:
- Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease globally.
- Current treatments for CAVD are limited in delaying disease progression.
- The precise molecular mechanisms underlying aortic valve calcification remain largely unknown.
Purpose of the Study:
- To identify differentially expressed genes and key molecular players in CAVD.
- To investigate the role of immune cell infiltration in the pathogenesis of CAVD.
- To uncover potential biomarkers and therapeutic targets for CAVD.
Main Methods:
- Utilized gene expression datasets (GSE12644, GSE51472) from the GEO database.
- Applied bioinformatics analyses including Gene Ontology (GO), KEGG pathway analysis, and protein-protein interaction (PPI) network construction.
- Performed immune infiltration analysis using CIBERSORT to assess immune cell proportions in CAVD.
Main Results:
- Identified 144 differentially expressed genes (DEGs) in CAVD, with 49 upregulated and 95 downregulated.
- GO analysis revealed enrichment in immune response, inflammation, and apoptosis pathways.
- KEGG analysis highlighted the chemokine signaling pathway, cytokine-cytokine receptor interaction, and PI3K-Akt signaling pathway.
- Key genes identified include chemokines CXCL13, CCL19, CCL8, CXCL8, CXCL16, MMP9, CCL18, CXCL5, VCAM1, and PPBP.
- Macrophages constituted the largest immune cell proportion, with increased M0, memory B cells, and plasma cells, and decreased naive B cells, activated NK cells, and M2 macrophages in CAVD valves.
Conclusions:
- Chemokines CXCL13, CXCL8, CXCL16, CXCL5, CCL19, CCL8, and CCL18 are significant markers for aortic valve disease.
- Macrophages M0, plasma cells, memory B cells, naive B cells, activated NK cells, and macrophages M2 are implicated in the development and progression of aortic valve stenosis.
- These identified chemokines and immune cells likely interact to regulate calcification in CAVD.
Abstract:
Background: Valvular heart disease is obtaining growing attention in the cardiovascular field and it is believed that calcific aortic valve disease (CAVD) is the most common valvular heart disease (VHD) in the world. CAVD does not have a fully effective treatment to delay its progression and the specific molecular mechanism of aortic valve calcification remains unclear. Materials and Methods: We obtained the gene expression datasets GSE12644 and GSE51472 from the public comprehensive free database GEO. Then, a series of bioinformatics methods, such as GO and KEGG analysis, STING online tool, Cytoscape software, were used to identify differentially expressed genes in CAVD and healthy controls, construct a PPI network, and then identify key genes. In addition, immune infiltration analysis was used via CIBERSORT to observe the expression of various immune cells in CAVD. Results: A total of 144 differential expression genes were identified in the CAVD samples in comparison with the control samples, including 49 up-regulated genes and 95 down-regulated genes. GO analysis of DEGs were most observably enriched in the immune response, signal transduction, inflammatory response, proteolysis, innate immune response, and apoptotic process. The KEGG analysis revealed that the enrichment of DEGs in CAVD were remarkably observed in the chemokine signaling pathway, cytokine-cytokine receptor interaction, and PI3K-Akt signaling pathway. Chemokines CXCL13, CCL19, CCL8, CXCL8, CXCL16, MMP9, CCL18, CXCL5, VCAM1, and PPBP were identified as the hub genes of CAVD. It was macrophages that accounted for the maximal proportion among these immune cells. The expression of macrophages M0, B cells memory, and Plasma cells were higher in the CAVD valves than in healthy valves, however, the expression of B cells naïve, NK cells activated, and macrophages M2 were lower. Conclusion: We detected that chemokines CXCL13, CXCL8, CXCL16, and CXCL5, and CCL19, CCL8, and CCL18 are the most important markers of aortic valve disease. The regulatory macrophages M0, plasma cells, B cells memory, B cells naïve, NK cells activated, and macrophages M2 are probably related to the occurrence and the advancement of aortic valve stenosis. These identified chemokines and these immune cells may interact with a subtle adjustment relationship in the development of calcification in CAVD.
