Role of augmented transferrin during the retraining for undeveloped left ventricle

Transposition of great arteries (TGA) is a common congenital heart disease. Left ventricle (LV) is rapidly regressing and pulmonary artery banding (PAB) is utilized to retrain the undeveloped LV. Hence, it offered a unique human disease model to investigate the process of LV hypertrophy under pressure overload. Eight late referred children with TGA were enrolled. The plasma was collected at the 30 min. before and 48 hrs after PAB, and 25 proteins were identified as having significant change in proteomic analysis. Transferrin (TF) and ceruloplasmin were then confirmed. After 48 hrs incubation with TF, the size of human induced pluripotent stem cell-derived cardiomyocytes increased by two times as large as control. Meanwhile, protein synthesis and the expression of natriuretic peptide precursor A and B were significantly enhanced. TF treatment also activated both extracellular signal-regulated kinase 1/2 and activated protein kinase singling pathways. Our data provided a link to molecular components and pathways that might be involved in LV retraining. TF severed as the carrier to delivery irons, and could directly stimulate cardiomyocytes hypertrophy. TF administration may hold therapeutic potential for the biological LV retraining.