Vascular Endothelial Growth Factor Accelerates Compensatory Lung Growth by Increasing Alveolar Units

BACKGROUND: Deficiency of vascular endothelial growth factor (VEGF) is associated with hypoplastic lung diseases such as congenital diaphragmatic hernia (CDH). Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced bronchopulmonary dysplasia and thus could induce lung growth and improve outcome in hypoplastic lung diseases. We aimed to determine the effects of exogenous VEGF in a rodent model of compensatory lung growth after left pneumonectomy. METHODS: Eight-ten-week-old C57Bl6 male mice underwent left pneumonectomy followed by daily intra-peritoneal injections of saline or VEGF (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric analyses were performed on post-operative day (POD) 4 and 10. Pulmonary expression of angiogenic factors was analyzed by quantitative polymerase chain reaction and western blot. RESULTS: Lung volume on POD 4 was higher in the VEGF-treated mice (P = 0.03). On morphometric analyses, VEGF increased parenchymal volume (P = 0.001), alveolar volume (P = 0.0003), and alveolar number (P < 0.0001) on POD 4. The VEGF group displayed higher levels of phosphorylated-VEGFR2/VEGFR2 (P = 0.03) and epidermal growth factor (EGF) mRNA (P = 0.01). CONCLUSION: VEGF accelerated compensatory lung growth in mice by increasing alveolar units. These changes may be mediated by VEGFR2 and EGF-dependent mechanisms.