title: Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma.
abstract: BACKGROUND
  Angiogenesis is a feature of airway remodeling in bronchial asthma. The mechanism responsible for this angiogenesis is unknown. Vascular endothelial growth factor (VEGF) is a potent inducer of endothelial cells, which may contribute to chronic inflammation and angiogenesis.
  
  
  OBJECTIVE
  We sought to investigate the molecular mechanisms underlying increased vascularity, and we examined the mRNA expression of VEGF and its receptors (flt-1 and flk-1) within bronchial biopsy specimens from asthmatic patients and normal control subjects.
  
  
  METHODS
  Endobronchial biopsy specimens were examined immunocytochemically by staining with anti-type IV collagen mAb to evaluate vessel density by using computer-assisted image analysis. Specimens were also analyzed for the presence of the mRNAs of VEGF and its receptors with in situ hybridization.
  
  
  RESULTS
  The extent of airway vascularity was increased in asthmatic subjects compared with that in control subjects (P <.01). Asthmatic subjects exhibited a greater expression of VEGF, flt-1, and flk-1 mRNA(+) cells in the airway mucosa compared with that in control subjects (P <.001 for each comparison). The degree of vascularity was associated with the number of VEGF, flt-1, and flk-1 mRNA(+) cells. Numbers of cells expressing VEGF mRNA inversely correlated with airway caliber (r = -0.83, P <.01) and airway hyperresponsiveness (r = -0.97, P <.001). Colocalization studies showed that macrophages, eosinophils, and CD34(+) cells were the major sources of VEGF; CD34(+) cells, macrophages, and T cells expressed both flt-1 and flk-1.
  
  
  CONCLUSIONS
  These findings provide evidence that VEGF may play an important role in angiogenesis and subsequent airway remodeling in bronchial asthma.
authors.affiliation: Second Department of Internal Medicine, Toho University School of Medicine, 6-11-1, Omori-nishi, Ota-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Q A
authors.initials: QA
authors.lastname: Hamid
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D001980:Bronchi / Q000098:blood supply* / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C501162:FLT1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1