Angiopoietins 1 and 2 in sputum supernatant of optimally treated asthmatics: the effect of smoking

Eur J Clin Invest. 2015 Jan;45(1):56-62. doi: 10.1111/eci.12379.

Abstract

Background: Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor.

Objective: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with optimally treated asthma and to investigate whether smoking represents a significant covariate on the above possible processes.

Methods: Eighty-seven patients with asthma (42 smokers) and 28 healthy subjects (14 smokers) were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of Ang-1, Ang-2, vascular endothelial growth factor, TGF-β1, MMP-2, IL-13, Eosinophilic cationic protein and IL-8 in supernatants. Airway vascular permeability (AVP) index was also assessed.

Results: Ang-1 (ng/mL) levels were significantly higher in patients with asthma compared to normal subjects. Smoking significantly increased Ang-1 levels [median, interquartile ranges 24 (13-37) in smoking asthmatics vs 10 (7-14) in nonsmoking asthmatics vs 5·3 (3·7-6·5) and 4·6 (3·8-5·7) in healthy smokers and nonsmokers, respectively, P < 0·001]. Similar results were observed for Ang-2 (pg/mL) [168 (132-203) vs 124 (82-152) vs 94 (78-113) vs 100 (96-108), respectively, P < 0·001]. Regression analysis in the whole study population showed a significant negative association for Ang-1, with AVP index, and MMP-2. Smoking was a significant covariate for both Ang-1 and Ang-2 in asthmatic patients.

Conclusions: Ang-1 and Ang-2 levels are upregulated in patients with optimally treated asthma. Our data support a possible role for smoking in the angiogenetic process in asthma.

Keywords: Angiogenesis; angiopoietins; asthma; inflammation; smoking.

MeSH terms

  • Adult
  • Angiopoietin-1 / metabolism*
  • Angiopoietin-2 / metabolism*
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Case-Control Studies
  • Forced Expiratory Volume / physiology
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neovascularization, Pathologic / pathology
  • Smoking / adverse effects*
  • Smoking / physiopathology
  • Sputum / chemistry
  • Vital Capacity / physiology

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • Anti-Asthmatic Agents
  • Matrix Metalloproteinase 2