Abstract
BackgroundHypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.MethodsIn the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (H2O2), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.ResultsHypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (H2O2) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.ConclusionThe findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H2O2 into the pulmonary vascular microenvironment.
Highlights
Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction
Effects of hypoxia on hemodynamics and pulmonary and systemic arterial wall remodeling right ventricle peak systolic pressure (RVSP) was measured by catheterization via jugular vein to right ventricle, which substitutes for the pulmonary artery pressure
Compared with the normoxic group, hypoxia promoted the proliferation of pulmonary artery smooth cells (PASMCs) (Fig. 3a, b) in vitro, but did not affect the proliferation of Aortic artery smooth cells (AASMCs) (Fig. 3c, d)
Summary
Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. We explored whether AECs are involved in pulmonary vascular remodeling and constriction. Alveolar hypoxia is primarily sensed at the alveolo capillary membrane, which is formed by juxtaposed epithelial and endothelial membranes in the alveolar wall, from where the hypoxic signal is propagated to pulmonary arterioles and subsequently triggers constriction of pulmonary artery smooth cells (PASMCs) [9]. The key role of endothelial cell-SMC crosstalk on HPH has been proposed [8, 11,12,13,14,15] It is almost unknown whether AECs are involved in the development of HPH.
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