Open AccessRole of Vascular Endothelial Growth Factor Signaling in Schistosoma ‐Induced Experimental Pulmonary Hypertension
Author(s) -
Chabon Jacob J.,
Gebreab Liya,
Kumar Rahul,
Debella Elias,
Tanaka Takeshi,
Koyanagi Dan,
Garcia Alexandra Rodriguez,
Sanders Linda,
Perez Mario,
Tuder Rubin M.,
Graham Brian B.
Publication year - 2014
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1086/675992
Subject(s) - inflammation , vascular endothelial growth factor , medicine , pulmonary hypertension , pathogenesis , immunology , lung , schistosoma mansoni , schistosomiasis , vascular endothelial growth factor c , vascular endothelial growth factor a , angiogenesis , immune system , cancer research , vegf receptors , helminths
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.