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- Title
Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2(+/-) Mice with Schistosomiasis.
- Authors
Crosby, Alexi; Soon, Elaine; Jones, Frances M.; Southwood, Mark R.; Haghighat, Leila; Toshner, Mark R.; Raine, Tim; Horan, Ian; Yang, Peiran; Moore, Stephen; Ferrer, Elisabet; Wright, Penny; Ormiston, Mark L.; White, R. James; Haight, Deborah A.; Dunne, David W.; Morrell, Nicholas W.
- Abstract
<bold>Rationale: </bold>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.<bold>Objectives: </bold>To determine whether Bmpr2(+/-) mice are more susceptible to schistosomiasis-induced pulmonary vascular remodeling.<bold>Methods: </bold>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.<bold>Measurements and Main Results: </bold>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 dilatation of the hepatic central vein at baseline and postinfection, compared with WT. Bmpr2(+/-) mice also showed significant dilatation of the liver sinusoids and an increase in inflammatory cells surrounding the central hepatic vein, compared with WT. This is consistent with an increase in the transhepatic passage of eggs.<bold>Conclusions: </bold>This study has shown that levels of BMPR-II expression modify the pulmonary vascular response to chronic schistosomiasis. The likely mechanism involves the increased passage of eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids in Bmpr2(+/-) mice. Genetically determined differences in the remodeling of hepatic vessels may represent a new risk factor for PAH associated with schistosomiasis.
- Subjects
ANIMAL experimentation; BIOLOGICAL models; CELL physiology; CELL receptors; CELLULAR signal transduction; LIVER; MICE; PULMONARY artery; PULMONARY hypertension; RESEARCH funding; SCHISTOSOMIASIS; TREMATODA; VASCULAR remodeling
- Publication
American Journal of Respiratory & Critical Care Medicine, 2015, Vol 192, Issue 11, p1355
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201412-2262OC