(a) : Normal lung development is interrupted in bronchopulmonary dysplasia (BPD). Preterm infants at risk of developing BPD are born at the late canalicular-early saccular stage of lung development. Factors contributing to BPD, such as preterm birth, inflammation, oxygen, mechanical ventilation, and steroids, interfere with the formation of alveoli resulting in large, simplified, and fewer distal airspaces. (b) Arrested alveolar development in BPD is associated with decreased angiogenesis. In experimental and human BPD, arrested alveolarization is associated with decreased lung angiogenesis and decreased vascular endothelial growth factor (VEGF) signaling. (c) Inhibition of angiogenesis impairs alveolarization. Conversely, during normal lung development, nonspecific and specific pharmacologic and genetic VEGF inhibition results in arrested alveolar development reminiscent of BPD. (d) VEGF-driven angiogenesis preserves and restores normal alveolarization in experimental BPD. Intratracheal adenovirus-mediated VEGF gene therapy or intraperitoneal VEGF peptide preserve and restore normal alveolar and lung vascular growth in oxygen-induced arrested alveolar development in newborn rats. Similar findings have been made with inhaled nitric oxide and pharmacologic hypoxia-inducible factor activation in preterm ventilated lambs or baboons.
Additional keywords: BPD,oxygen,VEGF,saccular,alveolar