The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension
Abstract Background 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. In this study, we e...
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doaj-3e197fa511b140b7bf0d18af6b2a938a2021-05-09T11:17:10ZengBMCRespiratory Research1465-993X2021-05-0122111610.1186/s12931-021-01708-wThe alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertensionYanxia Wang0Xiaoming Li1Wen Niu2Jian Chen3Bo Zhang4Xiumin Zhang5Yingmei Wang6Shaokang Dang7Zhichao Li8Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical UniversityDepartment of Pathophysiology, Xi’an Peihua UniversityDepartment of Pathophysiology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Respiratory and Critical Care, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pathophysiology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical UniversityDepartment of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical UniversityDepartment of Respiratory and Critical Care, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pathophysiology, School of Basic Medicine, Fourth Military Medical UniversityAbstract Background 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. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction. Methods In 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. Results Hypoxia 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. Conclusion The 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.https://doi.org/10.1186/s12931-021-01708-wAlveolar epithelial cellsHypoxic pulmonary hypertensionPulmonary vascular remodeling and constrictionReactive oxygen species |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yanxia Wang Xiaoming Li Wen Niu Jian Chen Bo Zhang Xiumin Zhang Yingmei Wang Shaokang Dang Zhichao Li |
spellingShingle |
Yanxia Wang Xiaoming Li Wen Niu Jian Chen Bo Zhang Xiumin Zhang Yingmei Wang Shaokang Dang Zhichao Li The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension Respiratory Research Alveolar epithelial cells Hypoxic pulmonary hypertension Pulmonary vascular remodeling and constriction Reactive oxygen species |
author_facet |
Yanxia Wang Xiaoming Li Wen Niu Jian Chen Bo Zhang Xiumin Zhang Yingmei Wang Shaokang Dang Zhichao Li |
author_sort |
Yanxia Wang |
title |
The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension |
title_short |
The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension |
title_full |
The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension |
title_fullStr |
The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension |
title_full_unstemmed |
The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension |
title_sort |
alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2021-05-01 |
description |
Abstract Background 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. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction. Methods In 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. Results Hypoxia 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. Conclusion The 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. |
topic |
Alveolar epithelial cells Hypoxic pulmonary hypertension Pulmonary vascular remodeling and constriction Reactive oxygen species |
url |
https://doi.org/10.1186/s12931-021-01708-w |
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