Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice

作者：Ming-Cheng Liu, Qiwang Liu, Yandong Pei, Miaomiao Gong, Xiaolin Cui, Jinjin Pan, Yunlong Zhang, Yang Liu, Ying Liu, Xiaocheng Yuan, Haoran Zhou, Yi‐Ying Chen, Jian Sun, Lin Wang, Xiya Zhang, Rui Wang, Shao Li, Jizhong Cheng, Yanchun Ding, Tonghui Ma, Yuhui Yuan · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2018 · DOI：10.1161/atvbaha.118.311714 · 被引用次数：51 · 研究领域：Pulmonary Hypertension Research and Treatments、ATP Synthase and ATPases Research、Mitochondrial Function and Pathology

Objective- Hypoxic pulmonary hypertension (HPH) is characterized by proliferative vascular remodeling. Abnormal pulmonary artery smooth muscle cells proliferation and endothelial dysfunction are the primary cellular bases of vascular remodeling. AQP1 (aquaporin-1) is regulated by oxygen level and has been observed to play a role in the proliferation and migration of pulmonary artery smooth muscle cells. The role of AQP1 in HPH pathogenesis has not been directly determined to date. To determine the possible roles of AQP1 in the pathogenesis of HPH and explore its possible mechanisms. Approach and Results- Aqp1 knockout mice were used, and HPH model was established in this study. Primary pulmonary artery smooth muscle cells, primary mouse lung endothelial cells, and lung tissue sections from HPH model were used. Immunohistochemistry, immunofluorescence and Western blot, cell cycle, apoptosis, and migration analysis were performed in this study. AQP1 expression was upregulated by chronic hypoxia exposure, both in pulmonary artery endothelia and medial smooth muscle layer of mice. Aqp1 deficiency attenuated the elevation of right ventricular systolic pressures and mitigated pulmonary vascular structure remodeling. AQP1 deletion reduced abnormal cell proliferation in pulmonary artery and accompanied with accumulation of HIF (hypoxia-inducible factor). In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration ability of primary cultured pulm...