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
05/11/2020Pubmed ID
32387780Pubmed Central ID
PMC7647938DOI
10.1053/j.semtcvs.2020.03.004Scopus ID
2-s2.0-85086171858 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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 RAuthors
Susan Foerster MD Professor in the Pediatrics department at Medical College of WisconsinTodd M. Gudausky MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Amy Y. Pan PhD 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 Associate Professor in the Pediatrics department at Medical College of Wisconsin
Karthikeyan Thirugnanam PhD Postdoctoral Researcher 5 in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ChildChild, Preschool
Endothelial Cells
Fontan Procedure
Hepatic Veins
Humans
Infant
Infant, Newborn
Lung
Vena Cava, Inferior
Vena Cava, Superior