Proteomic Study Reveals Plasma Protein Changes in Congenital Heart Diseases

Abstract

Congenital heart disease (CHD) is the most common birth defect in newborns. Plasma proteins may serve as indicators of disease and are a rich source for biomarker discovery, but little has been studied in CHD. We examined the hypothesis that plasma proteins may be altered and related to the pathologic changes of CHD. Differential protein analysis was performed in the plasma of patients with tetralogy of Fallot, isolated ventricular septal defect, and normal controls by using two-dimensional electrophoresis and mass spectrometry. Candidate proteins that might be related to disease processes were further confirmed by enzyme-linked immunosorbent assay in the new samples (n=40). Identified were 18 differentially expressed protein spots and 10 corresponding proteins or polypeptides. Among those, 2 downregulated proteins, gelsolin, ficolin-3, with significant clinical relevance, were further analyzed for validation. The plasma levels of gelsolin (76.30±4.42 vs 131.80±23.46 μg/mL in control; p=0.025, n=40 in each group) and ficolin-3 (4.93±0.36 vs 10.58±1.58 μg/mL in control; p=0.001, n=40 in each group) in tetralogy patients were significantly lower than those in normal controls. The ficolin-3 plasma level was also lower in the patients with isolated VSD (5.55±0.34 vs 10.58±1.58 μg/mL in control μg/mL; p=0.003, n=40 in each group). We used proteomic methods to demonstrate for the first time the plasma protein changes in CHD patients that may reveal the possible mechanisms for the prolonged bleeding time in tetralogy patients and the susceptibility to pulmonary infections in patients with CHDs. These findings have strong clinical implications.