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Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Identification of key genes in calcific aortic valve disease by integrated bioinformatics analysis
Peng Teng1, Xingjie Xu1, Chengyao Ni1
1Department of Cardiothoracic Surgery.
Abstract:
Calcific aortic valve disease (CAVD) is highly prevalent in our aging world and has no effective pharmaceutical treatment. Intense efforts have been made but the underlying molecular mechanisms of CAVD are still unclear.This study was designed to identify the critical genes and pathways in CAVD by bioinformatics analysis. Microarray datasets of GSE12644, GSE51472, and GSE83453 were obtained from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and functional and pathway enrichment analysis was performed. Subsequently, the protein-protein interaction network (PPI) was constructed with Search Tool for the Retrieval of Interacting Genes and was visualized with Cytoscape to identify the most significant module. Hub genes were identified by Cytoscape plugin cytoHubba.A total of 179 DEGs, including 101 upregulated genes and 78 downregulated genes, were identified. The enriched functions and pathways of the DEGs include inflammatory and immune response, chemotaxis, extracellular matrix (ECM) organization, complement and coagulation cascades, ECM receptor interaction, and focal adhesion. The most significant module in the PPI network was analyzed and genes among it were mainly enriched in chemotaxis, locomotory behavior, immune response, chemokine signaling pathway, and extracellular space. In addition, DEGs, with degrees ≥ 10 and the top 10 highest Maximal Chique Centrality (MCC) score, were identified as hub genes. CCR1, MMP9, VCAM1, and ITGAX, which were of the highest degree or MCC score, were manually reviewed.The DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the pathogenesis of CAVD and might serve as candidate therapeutic targets for CAVD.
Insights
Calcific aortic valve disease (CAVD) lacks effective treatments due to unclear molecular mechanisms. This study identifies key genes and pathways involved in CAVD, offering potential therapeutic targets for this prevalent condition.
Area of Science:
- Cardiovascular Biology
- Bioinformatics
- Genomics
Background:
- Calcific aortic valve disease (CAVD) is a growing global health concern, particularly in aging populations.
- Current pharmaceutical treatments for CAVD are ineffective, highlighting a critical need to understand its underlying molecular pathology.
- The precise molecular mechanisms driving CAVD progression remain largely elusive, impeding the development of targeted therapies.
Purpose of the Study:
- To elucidate the critical genes and molecular pathways implicated in the pathogenesis of calcific aortic valve disease (CAVD) using bioinformatics approaches.
- To identify potential novel therapeutic targets for CAVD by analyzing gene expression patterns and protein-protein interactions.
Main Methods:
- Utilized bioinformatics analysis of publicly available microarray datasets (GSE12644, GSE51472, GSE83453) from the Gene Expression Omnibus database.
- Identified differentially expressed genes (DEGs) and performed functional and pathway enrichment analyses.
- Constructed and analyzed a protein-protein interaction (PPI) network to identify significant modules and hub genes, including CCR1, MMP9, VCAM1, and ITGAX.
Main Results:
- Identified 179 differentially expressed genes (DEGs) in CAVD, comprising 101 upregulated and 78 downregulated genes.
- Enriched functions and pathways associated with DEGs include inflammatory response, immune response, extracellular matrix organization, and complement/coagulation cascades.
- Key hub genes, such as CCR1, MMP9, VCAM1, and ITGAX, were identified through PPI network analysis and are crucial for chemotaxis, immune response, and extracellular matrix interactions.
Conclusions:
- The identified DEGs and hub genes provide significant insights into the molecular mechanisms driving CAVD pathogenesis.
- These findings highlight potential candidate genes and pathways that could be targeted for the development of novel pharmaceutical treatments for calcific aortic valve disease.
- Further investigation into these molecular players may pave the way for effective therapeutic strategies against CAVD.
