Intestinal microcirculation and necrotizing enterocolitis: The vascular endothelial growth factor system

Necrotizing enterocolitis (NEC), a leading cause of morbidity and mortality in preterm neonates, is a devastating disease characterized by intestinal tissue inflammation and necrosis. NEC pathogenesis is multifactorial but remains unclear. Translocation of bacteria and/or bacterial products across a weak intestinal barrier in the setting of impaired mucosal immunity leads to an exaggerated inflammatory response and secondary mucosal epithelial injury. In addition to prematurity, other risk factors for NEC include congenital heart disease, maternal pre-eclampsia with placental vascular insufficiency, severe anemia and blood transfusion - all conditions that predispose the intestine to ischemia. We recently found that maldevelopment of the intestinal microvasculature plays an important role in NEC pathogenesis. Here we review the evidence supporting a role for defective development of the intestinal mucosal microvasculature and perturbations of intestinal blood flow in NEC, emphasizing the importance of vascular endothelial growth factor (VEGF) and the VEGF receptor-2 signaling pathway.