High concentrations of vascular endothelial growth factor reduce stretch-induced apoptosis of alveolar type II cells

Background and objective: Vascular endothelial growth factor (VEGF) is strongly expressed in the alveolar epithelium. VEGF has been shown to exhibit protective as well as injurious effects in ARDS/acute lung injury. We therefore investigated the influence of VEGF in a model of stretch-induced apoptosis. Methods: Isolated rat alveolar type II (ATII) cells were subjected to high-amplitude cyclic mechanical stretch (40 per minute, 30% change in surface area) for 24 h. VEGF gene expression was investigated by real-time reverse transcription-PCR. Concentrations of VEGF in culture supernatants of stretched cells were determined by ELISA. Apoptosis of cells following stretching was assessed by flow cytometry. Results: Vascular endothelial growth factor gene expression increased during the first 4 h of stretching and then declined to a similar level to that of static control cells. VEGF concentrations in cell supernatants increased in response to mechanical stretch, as compared with those in supernatants of static control cells. Incubation of ATII cells with higher concentrations of VEGF (50 ng/mL) during stretching inhibited apoptosis, presumably by restoring stretch-impaired phosphatidylinositol-3 kinase signalling. However, blocking free VEGF in the supernatant with an anti-VEGF antibody did not influence stretch-induced apoptosis. Conclusions: These findings suggest that high-amplitude mechanical stretch induced secretion of VEGF, which in high concentrations, may prevent stretch-induced apoptosis. In this model, however, the protective influence of VEGF was not essential for survival of ATII cells subjected to high-amplitude mechanical stretch.