Transcriptome analysis of right ventricular outflow tract myocardium in repaired-TOF patients with pulmonary regurgitation revealed the genetic features of right ventricle dysfunction

Abstract

Abstract Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. Surgical repair can prolong the survival time of TOF patients, but the right ventricle (RV) function of repaired-TOF (rTOF) patients will gradually deteriorate. Although pulmonary valve replacement (PVR) can delay the progression of RV dysfunction, it cannot avoid the ultimate RV failure. The purpose of this study was to define the genetic features of RV dysfunction in rTOF patients and to identify new potential biological targets for the treatment of RV dysfunction. Method: Comparative transcriptome analysis of RV outflow track (RVOT) myocardium specimens collected from rTOF patients was conducted. These patients were divided into two groups according to the period between initial surgical TOF repair and first PVR. The period less than 15 years was deemed as early PVR (PVRe), otherwise deemed as late PVR (PVRl). Total RNA isolated from each sample was use for functional enrichment/network analyses for differentially expressed genes (DGEs). Result: Six RVOT specimens (3 in PVRe and 3 in PVRl) showed significant differential expression of a total of 30 genes among which 15 genes were up-regulated and the other 15 genes were down-regulated in the comparison between PVRe and PVRl. According to Gene Ontology (GO) annotation, the mostly enriched biological processes was represented by monovalent inorganic cation transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated the significantly enriched signaling pathway was calcium signaling pathway. Both GO and KEGG highlighted the specific enrichment of inorganic cation transport gene in rTOF sample. Conclusion: This study presents the first global comparative transcriptome profiling of RV dysfunction in rTOF patients using RNA-seq and reveals the differernt gene expression pattern in rTOF patients. These findings have potential translational value because they identify new candidate prognostic markers and targets for the treatment of RV dysfunction in rTOF patients.