title: Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2(+/-) Mice with Schistosomiasis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Alexi
authors: http://orcid.org/0000-0001-5063-961X
authors: A
authors: Crosby
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Elaine
authors: E
authors: Soon
authors: 2 Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Frances M
authors: FM
authors: Jones
authors: 3 Department of Pathology, Papworth Hospital, Cambridge, United Kingdom.
authors: Mark R
authors: MR
authors: Southwood
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Leila
authors: L
authors: Haghighat
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Mark R
authors: MR
authors: Toshner
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Tim
authors: T
authors: Raine
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Ian
authors: I
authors: Horan
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Peiran
authors: P
authors: Yang
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Stephen
authors: S
authors: Moore
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Elisabet
authors: E
authors: Ferrer
authors: 4 Addenbrooke's Hospital, Cambridge, United Kingdom; and.
authors: Penny
authors: P
authors: Wright
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Mark L
authors: ML
authors: Ormiston
authors: 5 University of Rochester, Rochester, New York.
authors: R James
authors: RJ
authors: White
authors: 5 University of Rochester, Rochester, New York.
authors: Deborah A
authors: DA
authors: Haight
authors: 2 Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: David W
authors: DW
authors: Dunne
authors: 1 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Nicholas W
authors: NW
authors: Morrell
mesh_terms: D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000469:parasitology / Q000503:physiopathology*; D008099:Liver / Q000469:parasitology*; D051379:Mice; D011651:Pulmonary Artery / Q000469:parasitology / Q000503:physiopathology*; D012550:Schistosoma mansoni; D012552:Schistosomiasis / Q000235:genetics / Q000503:physiopathology*; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000235:genetics* / Q000502:physiology
chemical_list: C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: bone-morphogenetic protein type II receptor; pulmonary hypertension; pulmonary vascular remodeling; schistosomiasis