Conclusions
We are the first to correlate plasma angiogenic factor levels with angiography and in vitro angiogenic activity in patients with single ventricle disease with aortopulmonary collaterals. Patients with single ventricle disease have increased stromal-derived factor 1-alpha and soluble fms-like tyrosine kinase-1, and their roles in aortopulmonary collateral formation require further investigation. Plasma factors and angiogenic activity correlate poorly with aortopulmonary collateral severity in patients with single ventricles, suggesting complex mechanisms of angiogenesis.
Methods
In patients with single ventricle physiology (n = 27) and biventricular acyanotic control patients (n = 21), hypoxia-inducible angiogenic factor levels were measured in femoral venous and arterial plasma at cardiac catheterization. To assess plasma angiogenic activity, we used a 3-dimensional in vitro cell sprouting assay that recapitulates angiogenic sprouting. Aortopulmonary collateral angiograms were graded using a 4-point scale.
Results
Compared with controls, patients with single ventricle physiology had increased vascular endothelial growth factor (artery: 58.7 ± 1.2 pg/mL vs 35.3 ± 1.1 pg/mL, P < .01; vein: 34.8 ± 1.1 pg/mL vs 21 ± 1.2 pg/mL, P < .03), stromal-derived factor 1-alpha (artery: 1901.6 ± 1.1 pg/mL vs 1542.6 ± 1.1 pg/mL, P < .03; vein: 2092.8 pg/mL ± 1.1 vs 1752.9 ± 1.1 pg/mL, P < .02), and increased arterial soluble fms-like tyrosine kinase-1, a regulatory vascular endothelial growth factor receptor (612.3 ± 1.2 pg/mL vs 243.1 ± 1.2 pg/mL, P < .003). Plasma factors and sprout formation correlated poorly with aortopulmonary collateral severity. Conclusions: We are the first to correlate plasma angiogenic factor levels with angiography and in vitro angiogenic activity in patients with single ventricle disease with aortopulmonary collaterals. Patients with single ventricle disease have increased stromal-derived factor 1-alpha and soluble fms-like tyrosine kinase-1, and their roles in aortopulmonary collateral formation require further investigation. Plasma factors and angiogenic activity correlate poorly with aortopulmonary collateral severity in patients with single ventricles, suggesting complex mechanisms of angiogenesis.