Redox Signaling and Persistent Pulmonary Hypertension of the Newborn

Abstract

Reactive oxygen species (ROS) are redox-signaling molecules that are critically involved in regulating endothelial cell functions, host defense, aging, and cellular adaptation. Mitochondria are the major sources of ROS and important sources of redox signaling in pulmonary circulation. It is becoming increasingly evident that increased mitochondrial oxidative stress and aberrant signaling through redox-sensitive pathways play a direct causative role in the pathogenesis of many cardiopulmonary disorders including persistent pulmonary hypertension of the newborn (PPHN). This chapter highlights redox signaling in endothelial cells, antioxidant defense mechanism, cell responses to oxidative stress, and their contributions to disease pathogenesis.

Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches

“…Newborns are particularly at increased risk for amplified oxidative stress, since extrauterine alveolar oxygen tension is five times higher than that in utero. As such, the fetal lung, during late gestation, goes through adaptive increases in cellular antioxidant defenses, mostly superoxide dismutase-2 (SOD2) (111).…”

“…SOD2 expression is decreased in the pulmonary vasculature of PPHN human infants, as well as in the lamb model (122), contributing to endothelial dysfunction and impaired NOdependent vasodilation (122). This is not surprising, since SOD2 is the first line of defense against ROS, maintaining the balance of NO vs. superoxide during transition to extrauterine life (111). Accordingly, these observations had implications in the research for alternative therapies.…”