title: Pulmonary vascular remodeling correlates with lung eggs and cytokines in murine schistosomiasis.
abstract: BACKGROUND
  Schistosomiasis is considered to be the most common worldwide cause of pulmonary hypertension. At present there is no well-characterized animal model to study the pathobiology of this important condition.
  
  
  OBJECTIVE
  To develop a mouse model of schistosomiasis, characterize the extent of pulmonary vascular remodeling, and determine the potential role of inflammatory cytokines.
  
  
  METHODS
  Mice (C57/Bl6) were infected transcutaneously with a high dose (approximately 75-100 cercariae) or a low dose (approximately 30 cercariae) of Schistosoma mansoni, and the development of lung and liver pathology was studied in the subacute (high-dose) and chronic (low-dose) settings.
  
  
  RESULTS
  In the subacute setting, mice showed few eggs in the lungs and no evidence of pulmonary vascular remodeling. In contrast, chronically infected animals had a much greater lung egg burden and developed marked pulmonary vascular remodeling accompanied by perivascular inflammation from 12 weeks onwards. In addition, we observed the presence of plexiform-like lesions in these mice. Lung egg burden correlated with both liver egg burden and right ventricular (RV) index in the chronic group, although significant RV hypertrophy was lacking. Plasma Th1 and Th2 cytokines increased with time in the chronic group and correlated with the degree of pulmonary vascular remodeling.
  
  
  CONCLUSIONS
  This study provides evidence for extensive pulmonary vascular remodeling, despite the absence of RV hypertrophy, in a mouse model of schistosomiasis, including the formation of plexiform-like lesions. Inflammatory cytokines and lung egg burden may contribute to vascular lesion formation.
authors: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Alexi
authors: A
authors: Crosby
authors: Frances M
authors: FM
authors: Jones
authors: Mark
authors: M
authors: Southwood
authors: Susan
authors: S
authors: Stewart
authors: Ralph
authors: R
authors: Schermuly
authors: Ghazwan
authors: G
authors: Butrous
authors: David W
authors: DW
authors: Dunne
authors: Nicholas W
authors: NW
authors: Morrell
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008168:Lung / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010784:Photomicrography; D011651:Pulmonary Artery / Q000473:pathology*; D012550:Schistosoma mansoni / Q000302:isolation & purification*; D012552:Schistosomiasis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D016207:Cytokines