Tetralogy of Fallot (TOF) results in chronic progressive right ventricular (RV) pressure overload and shunt hypoxemia. We investigated the global changes in the proteome of RV among infant patients with and without TOF to gain an insight into early RV remodeling. One hundred and thirty-six differentially expressed proteins were identified using label-free LC-ESI-MS/MS analysis. Western blot results revealed that the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) increased significantly in TOF patients; and levels of lysocardiolipin acyltransferase 1 (LCLAT1), lumican (LUM), and versican (VCAN) decreased significantly. QRT-PCR analysis showed that levels of PFKFB2 mRNA were markedly increased, but those of LCLAT1 and LUM were significantly decreased. VCAN mRNA showed no significant change in response to pathophysiology of TOF. The results of immunohistochemical staining were similar to those of Western blot analysis. Results of the proteomic analysis indicated that the level of glycolysis-related proteins had increased and levels of lipid-metabolism-related proteins had decreased. ECM proteins were found to be more down-regulated in TOF in the present study than in previous reports. Taken together, our findings may provide clues to both the metabolic inflexibility and ECM remodeling during the early RV remodeling, which occur in response to chronic hypoxia and long-term pressure overload in TOF patients.
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