Figure 6.

Graphical abstract. Impaired BMPR2 signalling as a hallmark of early-stage vascular disease in the neonatal lung undergoing prenatal and postnatal injury, aggravated in the context of decreased PDGF-Rα signalling and persisting long term. We demonstrate that the exposure of the preterm lung to postnatal injury provokes an early and significant decrease in endothelial BMPR2 expression, mirrored by the joined reduction of BMP and PDGF plasma protein levels in preterm infants with a developing chronic pulmonary condition. Using multilayered preclinical models, we delineate the specific effects of the most prevalent prenatal and postnatal clinical risk factors and show early endothelial cell apoptosis and microvessel loss tied to a significant decrease in BMP signalling. The changes in BMP signalling persist long-term, are causally related to impaired PDGF-Rα expression driving septation defects and can be targeted therapeutically using an FDA approved drug. in part, the schematic was created using Servier medical art templates, creative commons Attribution V.3.0 Unported license; https://smart.servier.com. BMP, bronchopulmonary dysplasia; BMPR2; BMP receptor 2; CLD, chronic lung disease; FA, filtered air; FDA, US Food and Drug Administration; MV, mechanical ventilation; pCS, prenatal cigarette smoke.