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Hepatic Vein Blood Increases Lung Microvascular Angiogenesis and Endothelial Cell Survival-Toward an Understanding of Univentricular Circulation. Semin Thorac Cardiovasc Surg 2020 Winter;32(4):980-987

Date

05/11/2020

Pubmed ID

32387780

Pubmed Central ID

PMC7647938

DOI

10.1053/j.semtcvs.2020.03.004

Scopus ID

2-s2.0-85086171858   1 Citation

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.

Author List

Spearman AD, Gupta A, Pan AY, Gronseth EI, Thirugnanam K, Gudausky TM, Foerster SR, Ramchandran R

Authors

Susan Foerster MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Todd M. Gudausky MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Andrew Spearman MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin