Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.

<h4>Objective</h4>Calcific aortic valve disease (CAVD) is a progressive, age-related degenerative disease characterized by the accumulation of calcium deposits in the aortic valve. We aim to screen key genes associated with cellular senescence (CS) in CAVD.<h4>Methods</h4>The...

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Main Authors: Yijing Tao, Chengjie Gao, Juan Wang, Qiyin Zhang, Zhisong Wang, Leng Han, Donglai Cao, Qianwen Yao
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0318574
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author Yijing Tao
Chengjie Gao
Juan Wang
Qiyin Zhang
Zhisong Wang
Leng Han
Donglai Cao
Qianwen Yao
author_facet Yijing Tao
Chengjie Gao
Juan Wang
Qiyin Zhang
Zhisong Wang
Leng Han
Donglai Cao
Qianwen Yao
author_sort Yijing Tao
collection DOAJ
description <h4>Objective</h4>Calcific aortic valve disease (CAVD) is a progressive, age-related degenerative disease characterized by the accumulation of calcium deposits in the aortic valve. We aim to screen key genes associated with cellular senescence (CS) in CAVD.<h4>Methods</h4>The GSE12644 and GSE51472 datasets from the GEO database was utilized in this study, and differentially expressed genes (DEGs) were identified using the "limma" R package. CS-related DEGs (CS-DEGs) were determined through the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on CS-DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. The cytoHubba plug-in in Cytoscape was used to identify hub genes. A noncoding-RNA-mRNA regulatory network was established. DSigDB database was used to to identify drugs potentially be useful for treating CAVD.<h4>Results</h4>A total of 16 CS-DEGs were identified. These genes were primarily associated with collagen metabolic process, collagen catabolic process and external side of plasma membrane. 10 hub genes were identified as regulators of cellular senescence in CAVD: LPAR1, PTPN6, CD28, ID1, MEIS2, FGFR3, KDR, MMP7, AR, HIF1A. The Noncoding RNA-mRNA regulatory network indicated that CS-DEGs may be regulated by noncoding RNAs. β-Carotene, a naturally occurring carotenoid with antioxidant properties, was identified potential therapeutic agents through interacting with MMP9, MEIS2, and CTSB.<h4>Conclusion</h4>This study provides insights into the key genes and pathways related to cellular senescence in CAVD (MMP9, MEIS2, and CTSB) and highlights the potential role of β-Carotene treatment of CAVD.
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spelling doaj-art-6bdba48da24744e38b8f200cfdf3eedb2025-08-20T03:47:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e031857410.1371/journal.pone.0318574Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.Yijing TaoChengjie GaoJuan WangQiyin ZhangZhisong WangLeng HanDonglai CaoQianwen Yao<h4>Objective</h4>Calcific aortic valve disease (CAVD) is a progressive, age-related degenerative disease characterized by the accumulation of calcium deposits in the aortic valve. We aim to screen key genes associated with cellular senescence (CS) in CAVD.<h4>Methods</h4>The GSE12644 and GSE51472 datasets from the GEO database was utilized in this study, and differentially expressed genes (DEGs) were identified using the "limma" R package. CS-related DEGs (CS-DEGs) were determined through the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on CS-DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. The cytoHubba plug-in in Cytoscape was used to identify hub genes. A noncoding-RNA-mRNA regulatory network was established. DSigDB database was used to to identify drugs potentially be useful for treating CAVD.<h4>Results</h4>A total of 16 CS-DEGs were identified. These genes were primarily associated with collagen metabolic process, collagen catabolic process and external side of plasma membrane. 10 hub genes were identified as regulators of cellular senescence in CAVD: LPAR1, PTPN6, CD28, ID1, MEIS2, FGFR3, KDR, MMP7, AR, HIF1A. The Noncoding RNA-mRNA regulatory network indicated that CS-DEGs may be regulated by noncoding RNAs. β-Carotene, a naturally occurring carotenoid with antioxidant properties, was identified potential therapeutic agents through interacting with MMP9, MEIS2, and CTSB.<h4>Conclusion</h4>This study provides insights into the key genes and pathways related to cellular senescence in CAVD (MMP9, MEIS2, and CTSB) and highlights the potential role of β-Carotene treatment of CAVD.https://doi.org/10.1371/journal.pone.0318574
spellingShingle Yijing Tao
Chengjie Gao
Juan Wang
Qiyin Zhang
Zhisong Wang
Leng Han
Donglai Cao
Qianwen Yao
Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.
PLoS ONE
title Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.
title_full Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.
title_fullStr Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.
title_full_unstemmed Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.
title_short Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.
title_sort analysis of cellular senescence related genes in calcified aortic valve disease and the potential therapeutic role of β carotene
url https://doi.org/10.1371/journal.pone.0318574
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