Hepatic vein blood increases lung microvascular angiogenesis and survival – towards an understanding of univentricular circulation

OBJECTIVE: To improve our understanding of pulmonary arteriovenous malformations in univentricular congenital heart disease, our objective was to identify the effects of hepatic vein and superior vena cava constituents on lung microvascular endothelial cells independent of blood flow. METHODS: Paired blood samples were collected from the hepatic vein and superior vena cava in children 0-10 years-old undergoing cardiac catheterization. Isolated serum was subsequently used for in vitro endothelial cell assays. Angiogenic activity was assessed using tube formation and scratch migration. Endothelial cell survival was assessed using proliferation (BrdU incorporation, cell cycle analysis) and apoptosis (caspase 3/7 activity, Annexin-V labeling). Data were analyzed using Wilcoxon signed-rank test and repeated measures analysis. RESULTS: Upon incubating lung microvascular endothelial cells with 10% patient serum, hepatic vein serum increases angiogenic activity (tube formation, p=0.04, n=24; migration, p