Angiogenic growth factors in patients with cyanotic congenital heart disease and in normal children

Abstract

Previous studies have demonstrated that the expression of angiogenic growth factors is induced in hypoxic models. However, little is known about these factors in patients with cyanotic heart disease. The purpose of this study was to examine the relationship between the plasma level of angiogenic growth factors and the severity of cyanosis. The study included 85 patients with cyanotic heart disease and age matched 81 controls. Median age was 4.2 years in the cyanotic group and 4.8 years in the control group. Mean systemic oxygen saturation was 80.6±7.3% in the cyanotic group and 98.1±0.5% in the control group. In the control group, vascular endothelial growth factor (VEGF) in the neonatal period was significantly elevated, then rapidly decreased within 3 months after birth. After 3 months of age, VEGF levels remained at a plateau. In contrast, this age dependency did not occur in hepatocyte growth factor (HGF) levels. Although VEGF and HGF levels were not different between the cyanotic and control groups within 3 months after birth, the VEGF level in the cyanotic group after 3 months of age was significantly elevated compared to the levels measured in the control group (149.2±105.6 vs. 66.3±22.5 pg/ml, p<0.0001). Moreover, the VEGF level was negatively correlated with oxygen saturation (y=440.6-3.53x, R=0.47, p< 0.0001) in cases more than 3 months old. In contrast, no correlation was found between HGF level and oxygen saturation. Although physiologically increased VEGF in the neonatal period was rapidly decreased under normal oxygen saturation, a higher VEGF level persisted if systemic hypoxia was present. Persistently higher VEGF level may be related to the development of systemic to pulmonary collateral arteries in patients with cyanotic heart disease.