Role of vascular endothelial growth factor signaling in Schistosoma-induced experimental pulmonary hypertension

PVRI Member Authors: Rahul Kumar, Rubin Tuder, Brian Graham

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.

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Topics

Endothelin and Endothelium & Epithelium and Epithelial Transport
Immunology/ Immune Cell Signaling/ Inflammation/ Immunotherapy
Pulmonary Endothelium
Pulmonary Hypertension
Schistosomiasis

Authors

Jacob J. Chabon, Liya Gebreab, Rahul Kumar, Elias Debella, Takeshi Tanaka, Dan Koyanagi, Alexandra Rodriguez Garcia, Linda Sanders, Mario Perez, Rubin M. Tuder, Brian B. Graham

Published in:

Pulmonary Circulation Vol 4: No 2 cover image

May 2014

Pulmonary Circulation Vol 4: No 2

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