Related Experiment Video
Updated: May 12, 2026
Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography
Published on: October 28, 2020
Label-free quantitative proteomic analysis of right ventricular remodeling in infant Tetralogy of Fallot patients
Yu Xia1, Haifa Hong, Lincai Ye
1Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Insights
Tetralogy of Fallot (TOF) causes right ventricular (RV) pressure overload. This study reveals altered protein levels in RVs of infants with TOF, indicating metabolic inflexibility and extracellular matrix remodeling during early disease progression.
Area of Science:
- Cardiology
- Proteomics
- Molecular Biology
Background:
- Tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) pressure overload and hypoxemia.
- Early RV remodeling is crucial for understanding TOF progression.
Purpose of the Study:
- To investigate global proteomic changes in the RV of infant patients with and without TOF.
- To identify early molecular events contributing to RV remodeling in TOF.
Main Methods:
- Label-free liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) for proteomic analysis.
- Western blot, quantitative reverse transcription PCR (QRT-PCR), and immunohistochemical staining for protein and mRNA validation.
Main Results:
- Identified 136 differentially expressed proteins in TOF patients.
- Observed increased levels of glycolysis-related proteins (e.g., PFKFB2) and decreased levels of lipid metabolism-related proteins (e.g., LCLAT1, LUM).
- Found significant downregulation of extracellular matrix (ECM) proteins (e.g., VCAN) compared to previous reports.
Conclusions:
- Early RV remodeling in TOF is characterized by metabolic inflexibility, with a shift towards glycolysis.
- Significant ECM remodeling occurs in the RV during early stages of TOF.
- Findings provide insights into molecular mechanisms underlying RV dysfunction in TOF.
Abstract:
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.
