ArticleGenes2024
Side- and Disease-Dependent Changes in Human Aortic Valve Cell Population and Transcriptomic Heterogeneity Determined by Single-Cell RNA Sequencing.
Article in Genes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Digital phenotyping of aortic stenosis-related remodeling reveals complementary structural, electrical, and hemodynamic signatures.medRxiv : the preprint server for health sciences · 2026Article
- Immune Mechanisms of Heart Valve Development, Homeostasis, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Integrated bioinformatic analysis and experiments reveal EFEMP1 as a novel aging-related signature gene in calcific aortic valve disease.Scientific reports · 2026Article
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- Calcific aortic valve disease: can targeting endothelial-mesenchymal transition be a new alternative to surgery?-a narrative review.Cardiovascular diagnosis and therapy · 2026Review
- Single-nucleus and machine-learning integration identifies HLA-DRA and FTL as immune-metabolic axes and traditional Chinese medicine-targetable hubs in calcific aortic valve disease.Journal of computer-aided molecular design · 2026Article
- Activator protein-1 (AP-1) inhibition prevents endothelial to mesenchymal transition in diabetes-associated atherosclerosis: a translational study.Cardiovascular diabetology · 2026Article
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- A "Watchful Surgery" Approach: Timing and Valve Choice for Mildly Symptomatic Mitral and Aortic Valve Disease.Journal of surgery and research · 2025Article
- Integrated multi-omics analysis reveals key hub genes and mechanisms in calcific aortic stenosis.Frontiers in cardiovascular medicine · 2025Article
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Authors and funding
10 authors.
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Abstract
backgroundCalcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes.
methodsTo test this hypothesis, we performed single-cell RNA sequencing using a new method to collect endothelial-enriched samples independently from the fibrosa and ventricularis sides of freshly obtained human aortic valve leaflets from five donors, ranging from non-diseased to fibrocalcific stages.
resultsFrom the 82,356 aortic valve cells analyzed, we found 27 cell clusters, including seven valvular endothelial cell (VEC), nine valvular interstitial cell (VIC), and seven immune, three transitional, and one stromal cell population. We identified several side-dependent VEC subtypes with unique gene expression patterns. Homeostatic VIC clusters were abundant in non-diseased tissues, while VICs enriched with fibrocalcific genes and pathways were more prevalent in diseased leaflets. Furthermore, homeostatic macrophage (MΦ) clusters decreased while inflammatory MΦ and T-cell clusters increased with disease progression. A foamy MΦ cluster was increased in the fibrosa of mildly diseased tissues. Some side-dependent VEC clusters represented non-diseased, protective phenotypes, while others were CAVD-associated and were characterized by genes enriched in pathways of inflammation, endothelial-mesenchymal transition, apoptosis, proliferation, and fibrosis. Interestingly, we found several activator protein-1 (AP-1)-related transcription factors (
conclusionsOur results showed that VECs are highly heterogeneous in a side- and CAVD-dependent manner. Unique VEC clusters and their differentially regulated genes and pathways found in the fibrosa of diseased tissues may represent novel pathogenic mechanisms and potential therapeutic targets.
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