Regulatory effect of AMP-activated protein kinase on pulmonary hypertension induced by chronic hypoxia in rats: in vivo and in vitro studies

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• 作者：Xiaoying Huang (1)
  Rong Fan (2)
  Yuanyuan Lu (1)
  Chang Yu (3)
  Xiaomei Xu (1)
  Xie Zhang (1)
  Panpan Liu (1)
  Shuangquan Yan (1)
  Chun Chen (4)
  Liangxing Wang (1)
  
• 关键词：AMP ; activated protein kinase (AMPK) ; Hypoxia ; Pulmonary hypertension ; Vessel remodelling ; Pulmonary artery smooth muscle cells (PASMCs) ; 5 ; Aminoimidazole ; 4 ; carboxamide riboside (AICAR)
• 刊名：Molecular Biology Reports
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：41
• 期：6
• 页码：4031-4041
• 全文大小：
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• 作者单位：Xiaoying Huang (1)
  Rong Fan (2)
  Yuanyuan Lu (1)
  Chang Yu (3)
  Xiaomei Xu (1)
  Xie Zhang (1)
  Panpan Liu (1)
  Shuangquan Yan (1)
  Chun Chen (4)
  Liangxing Wang (1)
  
  1. Division of Pulmonary Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  2. Division of Pulmonary Medicine, Jiangdu People’s Hospital, Yangzhou, China
  3. Division of Radiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  4. Division of Pulmonary Medicine, Zhejiang People’s Hospital, Hangzhou, China
  
• ISSN：1573-4978

文摘

Activation of AMP-activated protein kinase (AMPK) plays an important role in cardiovascular protection. It can inhibit arterial smooth muscle cell proliferation and cardiac fibroblast collagen synthesis induced by anoxia. However, the role of AMPK-dependent signalling cascades in the pulmonary vascular system is currently unknown. This study aims to determine the effects of AMPK on pulmonary hypertension and pulmonary vessel remodelling induced by hypoxia in rats using in vivo and in vitro studies. In vivo study: pulmonary hypertension, right ventricular hypertrophy and pulmonary vascular remodelling were found in hypoxic rats. Meanwhile, AMPKα1 and phosphorylated AMPKα1 were increased markedly in pulmonary arterioles and lung tissues. Mean pulmonary arterial pressure, index of right ventricular hypertrophy and parameters of pulmonary vascular remodelling, including vessel wall area/total area, density of nuclei in medial smooth muscle cells, and thickness of the medial smooth muscle cell layer were markedly suppressed by AICAR, an AMPK agonist. In vitro study: the expression of AMPKα1 and phosphorylated AMPKα1 was increased in pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions. The effects of PASMC proliferation stimulated by hypoxia were reinforced by treatment with Compound C, an AMPK inhibitor. AICAR inhibited the proliferation of PASMCs stimulated by hypoxia. These findings suggest that AMPK is involved in the formation of hypoxia-induced pulmonary hypertension and pulmonary vessel remodelling. Up-regulating AMPK can contribute to decreasing pulmonary vessel remodelling and pulmonary hypertension induced by hypoxia.