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Updated: Jun 21, 2026
A Minimally Invasive Model of Aortic Stenosis in Swine
Published on: October 20, 2023
Molecular Mechanisms Underlying Recurrent Discrete Subaortic Stenosis: Insights From Bioinformatics Analysis of Human
Ravi K Birla1, Alyssa B Kalustian2, Lalita Wadhwa3
1Laboratory for Regenerative Tissue Repair, Texas Children's Hospital, Houston, Texas; Center for Congenital Cardiac Research, Texas Children's Hospital, Houston, Texas; Division of Congenital Heart Surgery, Texas Children's Hospital, Houston, Texas; Department of Surgery, Baylor College of Medicine, Houston, Texas; Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas.
Background:
Discrete subaortic stenosis (DSS) is characterized by fibrotic membrane formation in the left ventricular outflow tract and is associated with a high rate of postoperative recurrence requiring reoperation. Currently, no molecular markers exist to stratify recurrence risk. This study aimed to identify gene, protein, and pathway signatures associated with recurrent DSS using resected human tissue.
Methods:
This retrospective study analyzed fibrotic membrane specimens obtained from a congenital heart disease biobank. Tissue samples from 16 patients (17 samples) undergoing initial or repeated DSS resection with longitudinal clinical follow-up were analyzed. Patients were classified as nonaggressive DSS (no recurrence requiring reoperation within 5 years; n = 6) or aggressive DSS (recurrence requiring reoperation within 5 years; n = 11). Specimens were analyzed by bulk RNA sequencing, global proteomic profiling, and histologic evaluation. End points included differential gene, protein, and pathway expression associated with DSS recurrence.
Results:
Transcriptomic and proteomic analyses identified distinct molecular profiles between aggressive and nonaggressive DSS phenotypes. Aggressive DSS was associated with differential expression of genes and proteins involved in extracellular matrix remodeling, inflammation, and fibrotic signaling pathways. Pathway enrichment analyses demonstrated upregulation of epithelial to mesenchymal transition, transforming growth factor β signaling, and inflammatory pathways in aggressive disease. Histologic evaluation corroborated these findings, demonstrating increased fibroblast activation markers and newly synthesized collagen in aggressive DSS samples.
Conclusions:
Recurrent DSS is associated with distinct molecular signatures involving fibrotic and inflammatory pathways. These findings provide a biologic framework for recurrence risk stratification and identify candidate pathways for future mechanistic and translational studies.
