{"doi":"10.1053/j.semtcvs.2020.03.004","title":"Hepatic Vein Blood Increases Lung Microvascular Angiogenesis and Endothelial Cell Survival—Toward an Understanding of Univentricular Circulation","abstract":"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. 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. 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< 0.001, n = 18), increases proliferation (BrdU, P < 0.001, n = 32; S-phase, P = 0.04, n = 13), and decreases apoptosis (caspase 3/7, P < 0.001, n = 32; Annexin-V, P = 0.04, n = 12) compared to superior vena cava serum. Hepatic vein serum regulates lung microvascular endothelial cells by increasing angiogenesis and survival in vitro. Loss of hepatic vein serum signaling in the lung microvasculature may promote maladaptive lung microvascular remodeling and pulmonary arteriovenous malformations. 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. 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. 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< 0.001, n = 18), increases proliferation (BrdU, P < 0.001, n = 32; S-phase, P = 0.04, n = 13), and decreases apoptosis (caspase 3/7, P < 0.001, n = 32; Annexin-V, P = 0.04, n = 12) compared to superior vena cava serum. Hepatic vein serum regulates lung microvascular endothelial cells by increasing angiogenesis and survival in vitro. Loss of hepatic vein serum signaling in the lung microvasculature may promote maladaptive lung microvascular remodeling and pulmonary arteriovenous malformations. Central MessageHepatic vein serum differentially regulates the lung microvasculature in vitro compared to paired samples from the superior vena cava. These effects may prevent pulmonary arteriovenous malformations.Perspective StatementPulmonary arteriovenous malformations commonly form in children during surgical palliation for univentricular congenital heart disease, yet they remain poorly understand. The un-identified hepatic factor in hepatic vein blood prevents this complication. Here, we report a novel approach to characterize the effects of hepatic vein blood on the lung microvasculature and potentially identify hepatic factor. Hepatic vein serum differentially regulates the lung microvasculature in vitro compared to paired samples from the superior vena cava. These effects may prevent pulmonary arteriovenous malformations. Pulmonary arteriovenous malformations commonly form in children during surgical palliation for univentricular congenital heart disease, yet they remain poorly understand. The un-identified","journal":"Seminars in Thoracic and Cardiovascular Surgery","year":2020,"id":87444,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407561,"name":"Ankan Gupta","orcid":"0000-0003-0111-6294","position":1,"is_corresponding":false},{"id":444935,"name":"Amy Pan","orcid":"0000-0002-7199-7704","position":2,"is_corresponding":false},{"id":446175,"name":"Emily Gronseth","orcid":null,"position":3,"is_corresponding":false},{"id":316611,"name":"Karthikeyan Thirugnanam","orcid":"0000-0003-2832-2581","position":4,"is_corresponding":false},{"id":444936,"name":"Todd M. Gudausky","orcid":"0000-0002-1599-9393","position":5,"is_corresponding":false},{"id":444937,"name":"Susan Foerster","orcid":"0000-0003-2643-0730","position":6,"is_corresponding":false},{"id":316614,"name":"Ramani Ramchandran","orcid":"0000-0002-3555-6119","position":7,"is_corresponding":false},{"id":444934,"name":"Andrew D. Spearman","orcid":"0000-0003-2035-5258","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T22:00:29.831859Z","pmid":"32387780","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}