Endothelial metabolism in CDH: mitochondrial dysfunction as a new piece of the puzzle

Abstract

Congenital diaphragmatic hernia (CDH) remains one of the most challenging developmental lung diseases in neonatal medicine. Despite major advances in prenatal risk stratification, fetal intervention, neonatal intensive care, and extracorporeal support, pulmonary hypoplasia and pulmonary hypertension continue to determine morbidity and mortality. In this issue of Pediatric Research , Emrick and colleagues add an important dimension to the biology of CDH by showing that primary endothelial cells from affected newborns display a distinct mitochondrial phenotype characterized by metabolic activation, reduced bioenergetic efficiency, oxidative stress, and structural remodeling. 1 Their findings support a view of CDH not simply as a mechanically compressed lung, but as a developmental disorder in which intrinsic cellular abnormalities contribute to abnormal pulmonary growth and vascular adaptation.