ABSTRACT
Infants that die with pulmonary hypertension (PH) exhibit significant remodeling along the entire longitudinal axis of the pulmonary artery (PA). Hypoxia-induced remodeling of the neonatal PA and myocardium is distinct from the adult in multiple aspects, including observations that the proliferative and matrix producing potential of the neonatal pulmonary circulation in response to injury exceeds that of the adult. This is partly due to the fact that PH in children is intrinsically linked to issues of lung growth and development. The timing of the pulmonary vascular injury is a critical determinant of the response of the developing lung to multiple adverse stimuli, including hypoxia. Although inhaled nitric oxide (NO) and other PH-targeted drug therapies can improve the clinical course and outcomes of many newborns with diverse diseases associated with PH, some infants can develop progressive disease that is not responsive to traditional therapies. As a result, there is a pressing need to understand the pathobiology underlying the impact of hypoxia on the pulmonary circulation in neonates. Herein, we briefly review the current literature regarding the hypoxic remodeling of the neonatal pulmonary circulation and myocardium, including findings of augmented vascular cell proliferation, altered extracellular matrix (ECM) composition, and increased inflammation and, where possible, to provide the molecular basis for these responses. Our goal is to present a more integrated view of the impact of hypoxia responses in the neonatal heart and lung, which may ultimately lead to the development of therapeutic approaches explicitly directed at infants and children with PH.
