title: Regulatory effect of AMP-activated protein kinase on pulmonary hypertension induced by chronic hypoxia in rats: in vivo and in vitro studies.
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.
authors.affiliation: Division of Pulmonary Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China, zjwzhxy@126.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Huang
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Xu
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.forename: Panpan
authors.initials: P
authors.lastname: Liu
authors.forename: Shuangquan
authors.initials: S
authors.lastname: Yan
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.forename: Liangxing
authors.initials: L
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D066298:In Vitro Techniques; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012265:Ribonucleotides / Q000235:genetics / Q000494:pharmacology
chemical_list: D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat; C031143:AICA ribonucleotide