title: A potent anti-angiogenic factor, vasohibin-1, ameliorates experimental bronchiolitis obliterans.
abstract: BACKGROUND
  Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo.
  
  
  OBJECTIVE
  This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model.
  
  
  METHODS
  Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28.
  
  
  RESULTS
  Ad-VASH1 treatment reduced the vascular area on day 21 (4.6% versus 13.0%, P = .037) and day 28 (5.4% versus 13.4%, P = .022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69% versus 93%, P = .028) on day 21. We were not able to observe this effect on day 28 (92% versus 97%, P = .48).
  
  
  CONCLUSIONS
  Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.
authors.affiliation: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: S
authors.initials: S
authors.lastname: Eba
authors.forename: H
authors.initials: H
authors.lastname: Notsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Ohishi
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016377:Organ Transplantation / Q000009:adverse effects; D013997:Time Factors; D014132:Trachea / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
chemical_list: D018797:Cell Cycle Proteins; C493181:VASH1 protein, human