Fig. 3.

Schematic illustrating impaired formation of alveoli and lung capillaries and extracellular matrix (ECM) remodeling in wild-type (Eln^+/+) and elastin haploinsufficient (Eln^+/−) neonatal mice subjected to mechanical ventilation. Eln^+/− mice exhibit attenuated lung elastic fibers, increased collagen-1 and fewer capillaries at baseline. In wild-type mice, mechanical ventilation increases lung elastase activity and elastin degradation, leading to fragmented elastic fibers; however, no significant increase of lung elastase activity occurred in Eln^+/− mice. Instead, Eln^+/− mice exhibit reduced elastin synthesis and increased fibrillin production. In both genotypes, mechanical ventilation reduces abundance of the growth factors, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) and causes apoptosis and reduces the numbers of capillaries and alveoli, resulting in diminished lung growth and abnormal lung function. [Reproduced with permission from Ref. 97.]