The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension

• Published in: Respiratory research Vol. 22; no. 1; pp. 134 - 16
• Main Authors: Wang, Yanxia, Li, Xiaoming, Niu, Wen, Chen, Jian, Zhang, Bo, Zhang, Xiumin, Wang, Yingmei, Dang, Shaokang, Li, Zhichao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04-05-2021; BioMed Central; BMC
• Subjects: Acetylcysteine; Alveolar epithelial cells; Alveolar Epithelial Cells - metabolism; Alveolar Epithelial Cells - pathology; Alveoli; Animals; Carotid arteries; Catalase; Catalase - metabolism; Catheters; Cell culture; Cell growth; Cells, Cultured; Coculture Techniques; Complications and side effects; Constrictions; Culture media; Development and progression; Disease Models, Animal; Endothelium; Epithelial cells; Epithelium; Glucose; Health aspects; Hemodynamics; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hypertension; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Hypoxia; Hypoxia - complications; Hypoxic pulmonary hypertension; Inhibitors; Laboratory animals; Male; Medical research; Microenvironments; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Paracrine Communication; Paracrine signalling; Physical characteristics; Pressure effects; Pulmonary arteries; Pulmonary artery; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Pulmonary hypertension; Pulmonary vascular remodeling and constriction; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Signal Transduction; Smooth muscle; Superoxide dismutase; Superoxide Dismutase - metabolism; Vascular Remodeling; Vascular resistance; Vasoconstriction; Veins & arteries; China; United States > US; Colorado; Pulmonary vascular remodeling and constriction; Reactive oxygen species; Hypoxic pulmonary hypertension; Alveolar epithelial cells
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-021-01708-w

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.
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 (H
O
), 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.
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 (H
O
) 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.
The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H
O
into the pulmonary vascular microenvironment.