Heparin improves alveolarization and vascular development in hyperoxia-induced bronchopulmonary dysplasia by inhibiting neutrophil extracellular traps

Abstract

The objective of this study was to assess the role of NETs in BPD of hyperoxia-induced rat model and the effect of heparin on alveolarization and vascular development in BPD. The neonatal rats exposed to 90% oxygen continuously for 7 days to mimic BPD, meanwhile, the rats were injected by different doses of histones to evaluate the impact on lung injury. The newborn rats exposed to hyperoxia were injected by different doses of heparin (250 U/kg, 500 U/kg) or anti-H4 antibody to evaluate the effect of heparin. Histones and hyperoxia impaired alveolarization with the increase of mean linear intercept (MLI) and the decrease of radial alveolar count (RAC), decreased lung angiogenesis with the decrease expression of VEGF, and increased the expression of NETs, histones and pro-inflammatory factor. However, low dose heparin (250U/kg) administration enhanced survival, improved alveolarization and vascular development in hyperoxia-induced BPD, as well as reduced expression of NETs, histones and pro-inflammatory factor. We concluded that heparin improves alveolarization and vascularization in BPD by inhibiting NETs.

Keywords: Bronchopulmonary dysplasia; Heparin; Histones; Hyperoxia; Neutrophil extracellular traps.