Investigation of angiogenetic axis Angiopoietin-1 and -2/Tie-2 in fibrotic lung diseases: A bronchoalveolar lavage study

Increasing evidence implicates angiogenesis in the pathogenesis of fibrotic lung diseases. Distinct angiogenic profiles may, in part, explain differences in immunopathogenesis, clinical course and prognosis. The aim of the study was to seek evidence of involvement of the angiogenic axis Angiopoietin-1 and -2 and their tyrosine kinase receptor, Tie-2 in pathogenesis of idiopathic pulmonary fibrosis (IPF) and interstitial pneumonias associated to collagen tissue disorders (CTD-IPs). We prospectively studied 36 patients with IPF, 23 patients with CTD-IP and 10 healthy subjects. Ang-1, Ang-2 and Tie-2 mRNA expression and protein levels were measured in bronchoalveolar lavage fluid pellets and supernatants, respectively. A statistically significant decrease of Ang-1 protein level has been found in IPF in comparison to controls (p=0.02). We also detected an increased expression of Ang-2 protein in IPF in comparison to CTD-IPs. A significant co-expression was detected between Ang-2 and Tie-2 in protein level (p=0.007) in IPF group. In conclusion, a suppression of the angiogenetic factor Ang-1 was observed at the protein level in IPF which may be important in the pathogenesis of this devastating disease. A differential angiogenetic profile regarding Ang-2 was detected between IPF and CTD-IPs.