title: Role of vascular endothelial growth factor signaling in Schistosoma-induced experimental pulmonary hypertension.
abstract: There is significant evidence that Th2 (T helper 2)-mediated inflammation supports the pathogenesis of both human and experimental animal models of pulmonary hypertension (PH). A key immune regulator is vascular endothelial growth factor (VEGF), which is produced by Th2 inflammation and can itself contribute to Th2 pulmonary responses. In this study, we interrogated the role of VEGF signaling in a murine model of schistosomiasis-induced PH with a phenotype of significant intrapulmonary Th2 inflammation, vascular remodeling, and elevated right ventricular pressures. We found that VEGF receptor blockade partially suppressed the levels of the Th2 inflammatory cytokines interleukin (IL)-4 and IL-13 in both the lung and the liver after Schistosoma mansoni exposure and suppressed pulmonary vascular remodeling. These findings suggest that VEGF positively contributes to schistosomiasis-induced vascular inflammation and remodeling, and they also provide evidence for a VEGF-dependent signaling pathway necessary for pulmonary vascular remodeling and inflammation in this model.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Chabon
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Gebreab
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Debella
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Koyanagi
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rodriguez Garcia
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Sanders
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Perez
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA ; Pulmonary Vascular Research Institute.
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA ; Pulmonary Vascular Research Institute.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Graham
keywords: VEGF; inflammation; pulmonary hypertension; schistosomiasis