Angiopoietins 1 and 2 in sputum supernatant of optimally treated asthmatics: the effect of smoking.
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.
1st Respiratory Medicine Department, University of Athens Medical School, ″Sotiria″ Chest Hospital, Athens, Greece.
Vasiliki
V
Petta
Petros
P
Bakakos
Eleni
E
Tseliou
Konstantinos
K
Kostikas
Davina C M
DC
Simoes
Elissavet
E
Konstantellou
Georgios
G
Hillas
Nikolaos G
NG
Koulouris
Spyros
S
Papiris
Stelios
S
Loukides
D000328:Adult; D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016022:Case-Control Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology; D013183:Sputum / Q000737:chemistry; D014797:Vital Capacity / Q000502:physiology
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018927:Anti-Asthmatic Agents; D020778:Matrix Metalloproteinase 2
Angiogenesis; angiopoietins; asthma; inflammation; smoking