Role Of Vascular Endothelial Growth Factor And Angiopoietin-1 On The Airway Remodeling Of Asthma

Objective Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, lymphocttosis, mastocytosis infiltrate, hyperplasia of goblet cells and smooth muscle, subepithelial fibrosis and subucosal vascular proliferation. We examined the changes of VEGF and Ang-1 and its relation to the airway angiogenesis in a chronic asthma mouse model, and to explore the mechanism of the airway angiogenesiss and it's significance in airway remodeling.Methods Thirty BALB/c mice were randomly divided into three groups: normal control group (group A, n=10), chronic asthma group (group B, n=10), dexamethasone treated chronic asthma group (group C, n=10). We established the chronic asthma model mice by the allergen ovalbumin (OVA) intraperitoneal injection sensibilization and repeatedly atomize inhaled OVA challenge in group B. Mice in group A were sensitized and challenged with equal volume of NS substituted the OVA on the same days. Mice in group C received 2mg/kg dexamethasone intraperitoneal injection 1h before atomize inhalation OVA challenge every time. Twenty-four hours after the last challenge the mice were killed. Right lungs were lavaged and bronchoalveolar lavage fluid(BALF) were reserved. Left lungs and tracheae were fixed with 10% bufferedformalin and embedded in paraffin in 24h. Pathological slides were made from left lungs and bronchus and stained with hematoxylin-eosin(H-E),immunohistochemisry was employed to observe the expression and localization of VEGF and Ang-1.Results The density of vessels in tracheal lamina propria and submucosa,The airway wall basement membrane perimeter/total bronchial wall area (WAt/Pbm),The concentration of VEGF and Ang-1 in BALF B group higher than A group(P average< 0.01);C group lower than B group(P average< 0.01); C group higher than A group(P average< 0.05). There was a significant positively correlation between the density of vessels with WAt/Pbm and The concentration of VEGF in BALF.Conclusions Airway angiogenesis in the chronic asthma mice plays an important role in the airway remodeling. The airway angiogenesis might be the result of the excessive proliferation of angiogenic factors in the chronic asthma airway. Glucocorticoid can inhibit VEGF proliferation partly and attenuate the airway angiogenesis in chronic asthma mice, and then leads to restore the appropriate structure of airway well.