Hepatic Vein Blood Increases Lung Microvascular Angiogenesis and Endothelial Cell Survival-Toward an Understanding of Univentricular Circulation.
Hepatic Vein Blood Increases Lung Microvascular Angiogenesis and Endothelial Cell Survival-Toward an Understanding of Univentricular Circulation.
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DOI:
10.1053/j.semtcvs.2020.03.004
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发表时间:
2020
影响因子:
2.5
通讯作者:
Ramchandran R
中科院分区:
文献类型:
--
作者:
Spearman AD;Gupta A;Pan AY;Gronseth EI;Thirugnanam K;Gudausky TM;Foerster SR;Ramchandran R
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.
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