Transcriptome Analysis of Right Ventricular Outflow Tract Myocardium in Repaired TOF Patients with Pulmonary Regurgitation Revealed the Genetic Features of the Right Ventricle Dysfunction

Abstract 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 because of the residual pulmonary regurgitation (PR). Although pulmonary valve replacement (PVR) can delay the progression of RV dysfunction, it cannot avoid the ultimate RV failure. We conducted a comparative transcriptome analysis of RV outflow track (RVOT) myocardium specimens collected from 6 rTOF patients with PR to define the genetic features of RV dysfunction in this set of patients. We found significant differential expression of a total of 30 genes among which 15 genes were up-regulated and the other 15 genes were down-regulated. There differentially expressed genes were significantly enriched for the biological pathways ‘calcium signaling’, ‘cAMP signaling’, ‘Adrenergic signaling in cardiomyocytes’ and ‘Dopaminergic synapse’. This study presents the first global comparative transcriptome profiling of RV dysfunction using RNA-seq and reveals the different gene expression pattern in rTOF patients with PR. These findings have potential translational value because they identify new candidate prognostic markers and targets for the treatment of RV dysfunction.