Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets

Summary: Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease. Elucidating specific gene expression patterns in the aortic valve could provide new insights for understanding disease pathophysiology. We used local RNA sequencing data from 500 explanted human aortic valves to...

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Main Authors: Pardis Zamani, Ursula Houessou, Hasanga D. Manikpurage, Zhonglin Li, Manel Dahmene, Nathalie Gaudreault, François Dagenais, Marie-Annick Clavel, Philippe Pibarot, Benoit J. Arsenault, Patrick Mathieu, Yohan Bossé, Sébastien Thériault
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:HGG Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S266624772500051X
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author Pardis Zamani
Ursula Houessou
Hasanga D. Manikpurage
Zhonglin Li
Manel Dahmene
Nathalie Gaudreault
François Dagenais
Marie-Annick Clavel
Philippe Pibarot
Benoit J. Arsenault
Patrick Mathieu
Yohan Bossé
Sébastien Thériault
author_facet Pardis Zamani
Ursula Houessou
Hasanga D. Manikpurage
Zhonglin Li
Manel Dahmene
Nathalie Gaudreault
François Dagenais
Marie-Annick Clavel
Philippe Pibarot
Benoit J. Arsenault
Patrick Mathieu
Yohan Bossé
Sébastien Thériault
author_sort Pardis Zamani
collection DOAJ
description Summary: Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease. Elucidating specific gene expression patterns in the aortic valve could provide new insights for understanding disease pathophysiology. We used local RNA sequencing data from 500 explanted human aortic valves to identify aortic valve-specific genes and compared their expression according to disease status and CAVS severity. We identified 100 specific protein-coding genes in the aortic valve compared to 45 other tissues from the Genotype-Tissue Expression (GTEx) project. Among them, 38 were differentially expressed in CAVS. Ten had a gradient of expression between severity levels and were central in a protein-protein interaction network, most of which were involved in extracellular matrix regulation or inflammation. Among the aortic valve-specific genes, four of the corresponding proteins had a significantly different plasma level in individuals with CAVS. These findings represent a robust foundation for the development of specific biomarkers and therapies for CAVS.
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spelling doaj-art-e5e04395ba7746169db8dda1ea2dcf992025-08-20T03:13:26ZengElsevierHGG Advances2666-24772025-07-016310044810.1016/j.xhgg.2025.100448Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targetsPardis Zamani0Ursula Houessou1Hasanga D. Manikpurage2Zhonglin Li3Manel Dahmene4Nathalie Gaudreault5François Dagenais6Marie-Annick Clavel7Philippe Pibarot8Benoit J. Arsenault9Patrick Mathieu10Yohan Bossé11Sébastien Thériault12Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Surgery, Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Medicine, Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Medicine, Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Medicine, Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Surgery, Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Molecular Medicine, Université Laval, Quebec City, QC, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, QC, Canada; Corresponding authorSummary: Calcific aortic valve stenosis (CAVS) is the most frequent heart valve disease. Elucidating specific gene expression patterns in the aortic valve could provide new insights for understanding disease pathophysiology. We used local RNA sequencing data from 500 explanted human aortic valves to identify aortic valve-specific genes and compared their expression according to disease status and CAVS severity. We identified 100 specific protein-coding genes in the aortic valve compared to 45 other tissues from the Genotype-Tissue Expression (GTEx) project. Among them, 38 were differentially expressed in CAVS. Ten had a gradient of expression between severity levels and were central in a protein-protein interaction network, most of which were involved in extracellular matrix regulation or inflammation. Among the aortic valve-specific genes, four of the corresponding proteins had a significantly different plasma level in individuals with CAVS. These findings represent a robust foundation for the development of specific biomarkers and therapies for CAVS.http://www.sciencedirect.com/science/article/pii/S266624772500051Xcalcific aortic valve stenosistranscriptomicsbiomarkersgene expressionplasma proteins
spellingShingle Pardis Zamani
Ursula Houessou
Hasanga D. Manikpurage
Zhonglin Li
Manel Dahmene
Nathalie Gaudreault
François Dagenais
Marie-Annick Clavel
Philippe Pibarot
Benoit J. Arsenault
Patrick Mathieu
Yohan Bossé
Sébastien Thériault
Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
HGG Advances
calcific aortic valve stenosis
transcriptomics
biomarkers
gene expression
plasma proteins
title Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
title_full Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
title_fullStr Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
title_full_unstemmed Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
title_short Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
title_sort aortic valve specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets
topic calcific aortic valve stenosis
transcriptomics
biomarkers
gene expression
plasma proteins
url http://www.sciencedirect.com/science/article/pii/S266624772500051X
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