Project name: Transcriptome analysis defines ToF and ASD myocardial gene signatures and reveals disease-specific gene reprogramming upon surgery with cardiopulmonary bypass

Description: Tetralogy of Fallot (ToF) and Atrial Septal Defects (ASD) are the most common types of congenital heart disease and a major cause of childhood morbidity and mortality. Cardiopulmonary bypass (CPB) is used during corrective cardiac surgery to support circulation and heart stabilization. However, this technique triggers systemic inflammatory and stress response and consequent increased risk of postoperative complications. The aim of this study was to define the molecular bases of ToF and ASD pathogenesis and response to CPB and identify new specific biomarkers. We conducted comparative transcriptome analysis of right atrial biopsies from 10 ToF and 10 ASD patients before (Pre-CPB) and after (Post-CPB) surgery. Pre-CPB samples showed significant differential expression of 72 genes (DEGs), 28 of which were overexpressed in ToF and 44 in ASD. According to Gene Ontology annotation, the mostly enriched biological processes were represented by matrix organization and cell adhesion in ToF and by muscle development and contractility in ASD specimens. GSEA highlighted the specific enrichment of known hypoxia gene sets in ToF samples, pointing to a role for hypoxia in disease pathogenesis. The post-CPB myocardium exhibited significant alterations in the expression profile of genes related to transcription regulation, growth/apoptosis, inflammation, cell adhesion/matrix organization, and oxidative stress. Among DEGs, only 70 were common to the two disease groups, whereas 110 and 24 were unique in ToF and ASD, respectively. Interestingly, gene expression changes in ASD samples followed a consensus hypoxia profile. These data define ToF- and ASD-specific myocardial transcriptional signatures and demonstrate differential gene reprogramming in response to CPB in the two pathologies, with potential prognostic and therapeutic implications.Overall design: Transcriptome analysis of human atrial tissues from children affected by TOF or ASD following surgery with cardio-pulmonary bypass.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2019-06-04