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Angiopoietin-1 Protects against Airway Inflammation and Hyperreactivity in Asthma

Angiopoietin-1 Protects against Airway Inflammation and Hyperreactivity in Asthma,Davina C. M. Simoes,Theodoros Vassilakopoulos,Dimitrios Toumpanakis,

Angiopoietin-1 Protects against Airway Inflammation and Hyperreactivity in Asthma   (Citations: 9)
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Rationale: The angiopoietins (Ang) comprise a family of growth factors mainly known for their role in blood vessel formation and remodeling. The best-studied member, Ang-1, exhibits antiapop- totic and antiinflammatory effects. Although the involvement of Ang-1 in angiogenesis is well recognized, little information exists aboutitsroleinrespiratoryphysiologyanddisease.Onthebasisofits ability to inhibit vascular permeability, adhesion molecule expres- sion, and cytokine production, we hypothesized that Ang-1 admin- istration might exert a protective role in asthma. Objectives: To determine changes in the expression of Ang and to assesstheabilityofAng-1topreventthehistologic,biochemical,and functional changes observed in an animal model of asthma. Methods: To test our hypothesis, a model of allergic airway disease that develops after ovalbumin (OVA) sensitization and challenge was used. Measurements and Main Results: Ang-1 expression was reducedat the mRNA and protein levels in lung tissue of mice sensitized and challenged with OVA, leading to reduced Tie2 phosphorylation. IntranasalAng-1treatmentpreventedtheOVA-inducedeosinophilic lung infiltration, attenuated the increase in IL-5 and IL-13, and reduced eotaxin and vascular cell adhesion molecule 1 expression. These antiinflammatory actions of Ang-1 coincided with higher levels of IkB and decreased nuclear factor-kB binding activity. More importantly, Ang-1 reversed the OVA-induced increase in tissue resistance and elastance, improving lung function. Conclusions: We conclude that Ang-1 levels are decreased in asthma and that administration of Ang-1 might be of therapeutic value because it prevents the increased responsiveness of the airways to constrictors and ameliorates inflammation.
Published in 2008.
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