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Mécanismes de l’angiogénèse bronchique et de la synthèse de VEGF par l’épithélium respiratoire dans les dilatations des bronches.

Abstract : Abnormal proliferation of bronchial arteries in subjects with bronchiectasis contributes to the recruitment of inflammatory cells and plasma protein within the airways, and promotes endobronchial bleeding. Mechanisms of bronchial angiogenesis in bronchiectasis are largely unknown, but could implicate the vascular endothelial growth factor (VEGF)-A pathway.We hypothesized that bronchial infection that occurs in bronchiectasis contributes to angiogenesis of bronchial blood vessels. We developed a mouse model of persistent bronchial infection by intratracheal instillation of agarose beads containing Pseudomonas aeruginosa. Our results indicate that bacterial infection promotes angiogenesis of peribronchial blood vessels within 7 days. Further, P. aeruginosa induces VEGF-A synthesis in airway epithelium in vitro and in mouse in vivo via activation of the epidermal growth factor (EGF) receptor.Next we examined the role of CFTR defect, associated with cystic fibrosis (CF, a genetic cause of bronchiectasis), on bronchial angiogenesis and expression angiogenic growth factors. These studies were conducted using lung tissues obtained in CF subjects, in various strains of mice mutated for the cftr gene, and by inhibition of CFTR function in cultured airway epithelial cells.Our data indicate that bronchial infection contributes to peribronchial angiogenesis, which probably necessitate interaction of epithelial and endothelial cells. Cystic fibrosis airway epithelium may exhibit a pro-angiogenic phenotype in the absence of infection.
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Clémence Martin. Mécanismes de l’angiogénèse bronchique et de la synthèse de VEGF par l’épithélium respiratoire dans les dilatations des bronches.. Sciences agricoles. Université Paris-Est, 2010. Français. ⟨NNT : 2010PEST0030⟩. ⟨tel-00663307⟩

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