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Updated: Aug 13, 2026
Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
Published on: May 10, 2021
Programmed cell death-related transcriptomic features are associated with aortic valve calcification progression: an
Xianguan Yu1, Yunyue Zhao1, Zefeng Chen1
1Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Background:
Calcific aortic valve disease (CAVD) is an active, cell-mediated disorder lacking effective medical therapy. The contribution of programmed cell death (PCD) to disease progression remains insufficiently characterized. This study aimed to characterize PCD-related transcriptomic features during CAVD progression and identify candidate molecular indicators associated with disease severity.
Methods:
Transcriptomic datasets from aortic valve tissues were analyzed using differential expression, PCD activity scoring, weighted gene co-expression network analysis (WGCNA), Mfuzz clustering, and least absolute shrinkage and selection operator (LASSO) regression. A PCD-related gene signature was constructed and validated in an external cohort. Immune infiltration was profiled using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and peripheral blood leukocyte samples from patients with aortic valve disease were used for quantitative real-time polymerase chain reaction (qRT-PCR) validation.
Results:
PCD-related gene set enrichment increased progressively across disease stages (P=0.01). Integrative multi-step screening identified four key genes-CAV1, IGF1, IL7R, JAK1-forming a PCD-related signature. The risk score showed stepwise elevation from normal to mildly and severely calcified valves (P=8.7×10-5) and showed preliminary discriminative performance in both the training and validation cohorts. Immune infiltration analysis revealed significant remodeling, including increased M0 macrophages (P<0.01) and monocytes (P<0.05) and reduced M2 macrophages (P<0.05). Each signature gene correlated positively with major immune cell subsets (P<0.05). qRT-PCR showed mRNA-level upregulation of CAV1 and JAK1 (P<0.001) and downregulation of IGF1 (P<0.001) and IL7R (P<0.01) in peripheral blood leukocyte samples from patients with aortic valve disease.
Conclusions:
PCD-related transcriptomic enrichment was associated with aortic valve calcification severity and was accompanied by immune remodeling, although these changes may partly reflect overlapping inflammatory and cellular stress responses. The four-gene signature provides mechanistic insight into disease progression and represents a potential tool for molecular stratification and future therapeutic exploration.
