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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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Abstract

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.

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Acknowledgement

This study was supported by Zhejiang Provincial Natural Science Foundation of China (No. LY13H010003), http://www.zjnsf.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Liangxing Wang was sponsored by Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.

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Authors and Affiliations

  1. Division of Pulmonary Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Xiaoying Huang, Yuanyuan Lu, Xiaomei Xu, Xie Zhang, Panpan Liu, Shuangquan Yan & Liangxing Wang

  2. Division of Pulmonary Medicine, Jiangdu People’s Hospital, Yangzhou, China

    Rong Fan

  3. Division of Radiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Chang Yu

  4. Division of Pulmonary Medicine, Zhejiang People’s Hospital, Hangzhou, China

    Chun Chen

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  1. Xiaoying Huang
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  2. Rong Fan
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  4. Chang Yu
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  10. Liangxing Wang
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Correspondence to Xiaoying Huang or Liangxing Wang.

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Huang, X., Fan, R., Lu, Y. et al. Regulatory effect of AMP-activated protein kinase on pulmonary hypertension induced by chronic hypoxia in rats: in vivo and in vitro studies. Mol Biol Rep 41, 4031–4041 (2014). https://doi.org/10.1007/s11033-014-3272-9

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  • DOI: https://doi.org/10.1007/s11033-014-3272-9

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