Zamani Pardis, Houessou Ursula, Manikpurage Hasanga D, Li Zhonglin, Dahmene Manel, Gaudreault Nathalie, Dagenais François, Clavel Marie-Annick, Pibarot Philippe, Arsenault Benoit J, Mathieu Patrick, Bossé Yohan, Thériault Sébastien
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada.
Centre 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, Canada.
HGG Adv. 2025 May 5;6(3):100448. doi: 10.1016/j.xhgg.2025.100448.
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.
钙化性主动脉瓣狭窄（CAVS）是最常见的心脏瓣膜疾病。阐明主动脉瓣中的特定基因表达模式可为理解疾病病理生理学提供新的见解。我们使用了来自500个离体人主动脉瓣的局部RNA测序数据来鉴定主动脉瓣特异性基因，并根据疾病状态和CAVS严重程度比较它们的表达。与基因型-组织表达（GTEx）项目中的其他45个组织相比，我们在主动脉瓣中鉴定出100个特异性蛋白质编码基因。其中，38个在CAVS中差异表达。10个在严重程度水平之间具有表达梯度，并且在蛋白质-蛋白质相互作用网络中处于中心位置，其中大多数参与细胞外基质调节或炎症。在主动脉瓣特异性基因中，相应蛋白质中的4种在患有CAVS的个体中具有显著不同的血浆水平。这些发现为开发CAVS的特异性生物标志物和疗法奠定了坚实的基础。
