title: Vascular endothelial growth factor and cysteinyl leukotrienes in sputum supernatant of patients with asthma.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor in asthma. Cysteinyl leukotrienes (Cyst-LTs) have been implicated in vascular permeability in asthma. Cyst-LTs receptor antagonists modulate vascular permeability by reducing VEGF expression.
  
  
  OBJECTIVE
  We aimed to determine the levels of VEGF and Cyst-LTs in sputum supernatants of patients with asthma and to investigate possible associations within them and with airway vascular permeability (AVP) index. Possible confounding factors were also assessed.
  
  
  METHODS
  One hundred twenty one patients with asthma (38 with severe refractory asthma, 41 smokers) and 30 healthy subjects (15 smokers) were studied. All subjects underwent lung function tests, and sputum induction for cell count identification and VEGF, Cyst-LTs, measurement in supernatants. AVP index was also assessed.
  
  
  RESULTS
  Both VEGF & Cyst-LTs (pg/ml) levels were significantly elevated in patients with asthma compared to normal subjects (median, interquartile ranges 845 [487-1034] vs. 432 (327-654) and 209 [171-296] vs. 92 [75-114] respectively, p < 0.001 for both). Multivariate regression analysis in the whole group showed a significant association of Cyst-LTs levels in sputum supernatants with VEGF levels in sputum supernatants and AVP index. A similar positive association was observed between VEGF levels in sputum supernatants and AVP index. The presence of Severe asthma was a significant covariate for both associations.
  
  
  CONCLUSIONS
  Our results indicate that Cyst-LTs may modulate vascular permeability by up-regulating VEGF expression. The above effect seems to be affected by asthma severity.
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Sotiria Chest Hospital, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Papadaki
authors.forename: Petros
authors.initials: P
authors.lastname: Bakakos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostikas
authors.forename: Georgios
authors.initials: G
authors.lastname: Hillas
authors.forename: Zoi
authors.initials: Z
authors.lastname: Tsilogianni
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Koulouris
authors.forename: Spyros
authors.initials: S
authors.lastname: Papiris
authors.forename: Stelios
authors.initials: S
authors.lastname: Loukides
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D002199:Capillary Permeability / Q000502:physiology*; D016022:Case-Control Studies; D003545:Cysteine / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism / Q000503:physiopathology; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology; D012907:Smoking / Q000378:metabolism / Q000503:physiopathology; D013183:Sputum / Q000737:chemistry*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014797:Vital Capacity / Q000502:physiology
chemical_list: D015289:Leukotrienes; D042461:Vascular Endothelial Growth Factor A; C112381:cysteinyl-leukotriene; D003545:Cysteine
keywords: Angiogenesis; Asthma; Cysteinyl leukotrienes; Inflammation; VEGF; Vascular remodeling