Publication Date
8-1-2025
Journal
JTCVS Open
DOI
10.1016/j.xjon.2025.04.012
PMID
40923050
PMCID
PMC12414425
PubMedCentral® Posted Date
4-24-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Objective: Pediatric pulmonary vein stenosis (PVS) is associated with substantial morbidity and mortality for the subset of patients with recurrent or progressive disease. The molecular mechanisms underlying the development and trajectory of PVS remain unclear. This study characterizes the transcriptome of clinical and phenotypic subtypes of PVS.
Methods: Bulk RNA sequencing analysis was performed on human pulmonary vein tissue samples obtained from surgical interventions for pediatric patients with PVS. Transcriptomic profiles were compared for primary versus postrepair PVS as well as aggressive versus nonaggressive clinical phenotypes. Principal component analysis was performed, the differential gene expression quantified, and pathway analysis conducted on the basis of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome.
Results: When we compared aggressive (Agg) primary pulmonary vein stenosis (PPVS) versus nonaggressive (NonAgg) PPVS, differences were noted in the genes associated in extracellular matrix regulation and PIEZO1, a mechanosensitive receptor present in endothelial cells. In addition, there were notable changes in cardiac muscle contractility, calcium handling, respiratory and energy metabolism. These results point to a potential mechanism for aggressive PPVS phenotype, attributable to an overexpression of PIEOZ1 in response to elevated shear stress, subsequent activation of intracellular signaling pathways, and leading to reduced contractility and intracellular calcium transients within cardiomyocytes.
Conclusions: These results suggests that aggressive PPVS phenotype may be driven by an increase in PIEZO1 expression and subsequent changes in extracellular matrix production. The clinical and therapeutic relevance of PIEZO1 warrant further investigation.
Keywords
pulmonary vein stenosis, bulk RNA sequencing, PIEZO1, Gene Ontology analysis, REACTOME, KEGG, congenital heart disorder
Published Open-Access
yes
Recommended Citation
Kalustian, Alyssa B; Ji, Pengfei; Wadhwa, Lalita; et al., "Insights Into the Molecular Mechanism of Pulmonary Vein Stenosis in Pediatric Patients With Congenital Heart Disease" (2025). Faculty and Staff Publications. 5698.
https://digitalcommons.library.tmc.edu/baylor_docs/5698
Included in
Allergy and Immunology Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Pathology Commons