Abstract 15182: Proteomic Study Reveals Plasma Protein Changes in Congenital Heart Diseases and Potential Clinical Significance
Background: Congenital heart disease (CHD) is the most common birth defect in newborns. Plasma proteins may often serve as indicators of disease and is a rich source for biomarker discovery but little has been studied in CHD. The present proteomic study examined the hypothesis that plasma proteins may be altered and related to the pathological changes of CHD. Such alterations might be useful in development of biomarkers in the diagnosis and treatment of CHD.
Methods & Results: Proteomic analysis was performed in the plasma of patients with tetralogy of Fallot (TOF), isolated ventricular septal defect (VSD) and normal controls by using two-dimensional electrophoresis (2-DE) and mass spectrometry. Candidate proteins that might be related to disease processes were further confirmed by enzyme-linked immunosorbent assays (ELISA) in the new samples (n=40). Eighteen differentially expressed protein sports and 10 corresponding proteins or polypeptides were identified by 2-DE and mass spectrometry. Among those, two down-regulated proteins (gelsolin, ficolin-3) had significant clinical relevance. Gelsolin is related to rapid platelet activation and shape changes and ficolin-3 is a recognition molecule in the lectin-pathway of the complement system and plays an important role in innate immunity. These two proteins were further analyzed as candidate proteins for validation and measured by ELISA. The plasma gelsolin (76.30±4.42 vs. 131.80±23.46 μ g/ml in control, P=0.025, n=40 in each group) and ficolin-3 (4.93 ± 0.36 vs. 10.58±1.58 μ g/ml in control, P=0.001, n=40 in each group) levels in TOF 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 μ g/ml in control, P=0.003, n=40 in each group).
Conclusions: In the present study we have for the first time, by using proteomic methods, demonstrated the plasma protein changes in CHD patients. Our study may reveal the possible reasons for the prolonged bleeding time in TOF patients and the susceptibility to pulmonary infections in patients with CHDs.
- © 2012 by American Heart Association, Inc.