Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2+/− Mice with Schistosomiasis

Rationale: Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are the commonest genetic cause of PAH.Objectives: To determine whether Bmpr2+/− mice are more susceptible to schistosomiasis-induced pulmonary vascular remodeling.Methods: Wild-type (WT) and Bmpr2+/− mice were infected percutaneously with Schistosoma mansoni. At 17 weeks postinfection, right ventricular systolic pressure and liver and lung egg counts were measured. Serum, lung and liver cytokine, pulmonary vascular remodeling, and liver histology were assessed.Measurements and Main Results: By 17 weeks postinfection, there was a significant increase in pulmonary vascular remodeling in infected mice. This was greater in Bmpr2+/− mice and was associated with an increase in egg deposition and cytokine expression, which induced pulmonary arterial smooth muscle cell proliferation, in the lungs of these mice. Interestingly, Bmpr2+/− mice demonstrated dilat...