Abstract Body (Do not enter title and authors here): Introduction: Pulmonary arteriovenous malformations (PAVM) development severely limits the long-term durability of the corrective surgical treatment and survival for univentricular congenital heart disease. PAVM increased incidence has been clearly associated with hepatopulmonary interruption, nevertheless the underlying mechanisms remain unclear. In vitro disease models offer a promising tool to study PAVM.
Hypothesis: Superior vena cava (SVC) and hepatic vein (HV) may have distinct angiogenic capacities leading to PAVM development after hepatopulmonary interruption post Glenn.
Goals: To compare the angiogenic effects of plasma from superior vena cava (SVC) and hepatic vein (HV) on endothelial cells as an initial approach to understand PAVM development.
Methods: Plasma was extracted from SVC and HV full blood samples of 10 patients with different congenital heart defects (0-2 years old). Plasma angiogenic potential was compared using in vitro 2D arteriovenous endothelial migration and tube formation assays, and a 3D organ-on-chip model.
Results: Clear differences regarding the angiogenic potential of SVC vs HV were evidenced. In 2D, all plasma supplemented conditions showed increased arteriovenous cell migration (p=0.002) and tube formation potential (p=0.0001) compared to control. However, HV plasma showed a significantly impaired cell migration induction and tube formation capacity compared to SVC and physiological condition (SVC and HV) (p＜0.05). While 2D assays showed no difference between SVC and combined SVC+HV supplementation, the 3D MultiCUBE organ on a chip revealed that combined plasma suppressed angiogenesis, while individual SVC or HV plasma differentially promoted it, with special increase in SVC.
Conclusion: In vitro models reveal that angiogenesis is modulated by a balance between SVC and HV plasma-derived signals. In vitro arteriovenous models provide valuable insight into the cellular mechanisms driving PAVM development.