sVEGFR1 Is Enriched in Hepatic Vein Blood-Evidence for a Provisional Hepatic Factor Candidate? Front Pediatr 2021;9:679572
Date
07/02/2021Pubmed ID
34195162Pubmed Central ID
PMC8236596DOI
10.3389/fped.2021.679572Scopus ID
2-s2.0-85115450112 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Background: Pulmonary arteriovenous malformations (PAVMs) are common sequelae of palliated univentricular congenital heart disease, yet their pathogenesis remain poorly defined. In this preliminary study, we used paired patient blood samples to identify potential hepatic factor candidates enriched in hepatic vein blood. Methods: Paired venous blood samples were collected from the hepatic vein (HV) and superior vena cava (SVC) from children 0 to 10 years with univentricular and biventricular congenital heart disease (n = 40). We used three independent protein analyses to identify proteomic differences between HV and SVC blood. Subsequently, we investigated the relevance of our quantified protein differences with human lung microvascular endothelial assays. Results: Two independent protein arrays (semi-quantitative immunoblot and quantitative array) identified that soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is significantly elevated in HV serum compared to SVC serum. Using ELISA, we confirmed the previous findings that sVEGFR1 is enriched in HV serum (n = 24, p < 0.0001). Finally, we studied the quantified HV and SVC serum levels of sVEGFR1 in vitro. HV levels of sVEGFR1 decreased tip cell selection (p = 0.0482) and tube formation (fewer tubes [p = 0.0246], shorter tube length [p = 0.0300]) in vitro compared to SVC levels of sVEGFR1. Conclusions: Based on a small heterogenous cohort, sVEGFR1 is elevated in HV serum compared to paired SVC samples, and the mean sVEGFR1 concentrations in these two systemic veins cause pulmonary endothelial phenotypic differences in vitro. Further research is needed to determine whether sVEGFR1 has a direct role in pulmonary microvascular remodeling and PAVMs in patients with palliated univentricular congenital heart disease.
Author List
Spearman AD, Gupta A, Pan AY, Gudausky TM, Foerster SR, Konduri GG, 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
Girija Ganesh Konduri MD Chief, 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 Assistant Professor in the Pediatrics department at Medical College of Wisconsin
