Alveolar Epithelial Cells Involved in Pulmonary Vascular Remodeling and Constriction of Hypoxic Pulmonary Hypertension

Abstract Background: Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension. Alveolar epithelial cells (AECs) are the first to perceive hypoxia of alveolar, however, the role of AECs in HPH remain unclear. HPH is characterized by pulmonary vascular remodeling and constriction. The present study was to whether AECs was involved in pulmonary vascular remodeling and constriction.Methods: Rat HPH models were built and pulmonary artery smooth cells (PASMCs) and AECs were treatment with hypoxia. Hemodynamic and morphological indicators were measured in samples from rat HPH models. Superoxide dismutase 2 (SOD2), catalase (CAT) and reactive oxygen species (ROS) were detected in AECs or AECs culture medium. To find out the effect of AECs on pulmonary vascular remodeling and constriction, AECs and PASMCs were co-cultured under hypoxia, PASMCs and isolated pulmonary artery (PA) were treatment with AECs hypoxic culture medium. To explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.Results: In vivo, hypoxia resulted in elevation in pulmonary vascular remodeling and pressure, but had no effect on non-pulmonary vascular. In vitro, hypoxia caused an imbalance of superoxide dismutase 2 (SOD2) and catalase (CAT) and an increase of reactive oxygen species (ROS) in AECs, as well as an increase of hydrogen peroxide (H2O2) in AECs culture medium. Also, AECs led to pulmonary artery smooth cells (PASMCs) proliferation under hypoxia by co-culture or substituting culture medium. AECs hypoxic culture medium enhanced the constriction of isolated pulmonary artery (PA). Further, these responses were abrogated by ROS inhibitor N-acetylcysteine (NAC). Conclusion: The findings of present study demonstrated that AECs involved in pulmonary vascular remodeling and constriction under hypoxia by secreting H2O2 to the pulmonary microenvironment.