Transcriptome analysis in rTOF patients determined the RVOT myocardium gene expression and revealed the genetic features of RV dysfunction progression

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. From the genetic perspective, the etiology of TOF is multifactorial. Despite successful surgical repair, many patients have chronic volume and pressure loading leading to a 40% probability of right ventricular (RV) failure by the 3rd decade of life. In addition, some patients developed RV failure before 30 years of age. Heart failure in repaired TOF (rTOF) is recognized as a significant complication. Its occurrence is strongly associated with adverse outcome. Although pulmonary valve replacement (PVR) can delay and improve RV failure, the optimal timing of PVR is still unknown because of the unnatural history of rTOF. Therefore, it is necessary to better understand the molecular and cellular mechanisms which lead to progressive RV enlargement and dysfunction in rTOF patients.Messenger RNA (mRNA) are coding RNA is a single-stranded nucleotides that carries genetic information to guide protein synthesis which are transcripted from one strand of DNA. Messenger RNA accounts for only 2%-5% of the total RNA of human cells, but it widest in variety and most active in metabolism. Based on its rapid expression, simple sequence composition, low immunogenicity and flexible modification, great progress has been made in mRNA therapy which has been used in the treatment of rare genetic metabolic diseases. The research on mRNA therapy for heart disease is in progress, so mining the mRNA profile of RV in rTOF patients is helpful to find potential therapeutic targets and provide necessary theoretical basis of mRNA therapy for RV dysfunction in rTOF patients.We hypothesized that mRNA profiles in RV cardiomyocyte would provide insight into the mechanism of disease progression which could then aid in risk stratification and early prediction of RV failure in rTOF patients. For this purpose, we used RNA-seq to analyze the data pertaining to expression levels and performed high-resolution transcriptome analyses of the myocardial tissue of RV. The RNA-seq library was sequenced using the DNBSEQ platform, which uses the DNA nanoball technology.