Am J Respir Cell Mol Biol. 2025 Aug 22. doi: 10.1165/rcmb.2025-0009OC. Online ahead of print.
ABSTRACT
Bronchopulmonary dysplasia is a chronic lung disease that affects preterm infants. Disrupted microvascular growth is a well-recognized pathologic feature of BPD, which plays a critical role in arrested alveologenesis. Recent studies have identified two subpopulations of pulmonary microvascular endothelial cells (ECs): general capillary (gCap) and aerocyte (aCap). In this study, we validated proposed markers for gCap (GPIHBP1, PLVAP, CD93) and aCap (CA4, HPGD) at the protein level and investigated their abundance during late-stage lung development in murine and non-human primate (NHP) lungs. We also examined alterations in the abundance and proliferation of gCap and aCap in NHP and murine models of BPD. Our studies confirmed CA4 and HPGD as specific markers for aCap, while all three putative gCap markers were also detected in non-microvascular endothelial cells. All markers, except for HPGD, showed a gradual increase in abundance during the saccular and alveolar stages of development in NHP lungs. In the NHP model of BPD, the abundance of both aCap markers and GPIHBP1 were decreased, while that of PLVAP and CD93 were increased. Additionally, there was an emergence of CA4+HPGD–-aCap in BPD lungs. In late-stage control lungs, aCap proliferation was more robust than gCap proliferation, while no significant differences were observed between aCap and gCap proliferation rates in NHP BPD. Notably, in BPD lungs, gCap proliferation was more robust compared to control lungs. This study provides new insights into the distinct regulation patterns of microvascular ECs during lung development and neonatal lung injury in a translationally relevant NHP model.
PMID:40845320 | DOI:10.1165/rcmb.2025-0009OC
