Identification of Key Genes and Pathways in Calcific Aortic Valve Disease by Bioinformatics Analysis

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2020 Feb 8

PMID 32030260

Citations 12

Authors

Yiran Zhang

Liang Ma

Affiliations

Soon will be listed here.

Abstract

Background: Calcific aortic valve disease (CAVD) is the most common type of valvular heart disease in the elderly. This study is aimed to explore molecular mechanism of CAVD via bioinformatics analysis.

Methods: The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using the MetaDE package in R software. Functional and pathway enrichment analysis were performed based on Gene ontology (GO) and KEGG pathway database. Then, STRING database, Cytoscape and MCODE were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Pathway enrichment analysis was further performed for hub genes and gene clusters identified via module analysis.

Results: A total of 107 DEGs were identified in CAVD (53 up-regulated genes, and 54 down-regulated genes), and they were mainly enriched in the terms of immune response, extracellular matrix organization, leukocyte transendothelial migration, cell adhesion molecules (CAMs), and fatty acid metabolism. Five hub genes including VCAM1, MMP9, ITGB2, RAC2, and vWF were identified via PPI network, which were mainly enriched in terms of leukocyte transendothelial migration and cell adhesion. An independently down-regulated protein cluster containing ALDH2, HIBCH, ACADVL, ECHDC2, VAT1L, and MAOA was also identified via PPI network.

Conclusions: The present study identified VCAM1, MMP9, ITGB2, RAC2, vWF and ALDH2 as key genes in the progression of CAVD. Immune cells infiltration might play a key role in the progression of CAVD, while ALDH2-mediated detoxification effect might play a protective role in CAVD. Further studies are needed to elucidate the pathogenesis of CAVD.

Citing Articles

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Identifying hub genes of calcific aortic valve disease and revealing the immune infiltration landscape based on multiple WGCNA and single-cell sequence analysis.

Wang K, Zheng Q, Liu X, Geng B, Dong N, Shi J Front Immunol. 2022; 13:1035285.

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Transcriptome Sequencing Data Reveal LncRNA-miRNA-mRNA Regulatory Network in Calcified Aortic Valve Disease.

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Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth muscle cells from adult mouse heart.

Cao Z, Minnier J, Liu L, Scott K, Reddy A, Wilmarth P Sci Rep. 2022; 12(1):8835.

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Profiling Genome-Wide DNA Methylation Patterns in Human Aortic and Mitral Valves.

Halawa S, Latif N, Tseng Y, Ibrahim A, Chester A, Moustafa A Front Cardiovasc Med. 2022; 9:840647.

PMID: 35463757 PMC: 9019152. DOI: 10.3389/fcvm.2022.840647.

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