title: Potential therapeutic targets for hypoxia-induced pulmonary artery hypertension.
abstract: BACKGROUND
  Hypoxic pulmonary artery hypertension (PAH) as a severe pulmonary disease is characterized by changes of pulmonary vascular reconstruction. Mitochondrial ATP-sensitive potassium channel (mitoKATP) was considered as one of factors responsible for the proliferation of hypoxic pulmonary arterial smooth muscle cells (PASMCs), although the exact mechanisms remain unclear.
  
  
  METHODS
  Pulmonary artery hypertension was induced in rats with or without 5-hydroxydecanoate (5-HD). The mean pulmonary artery pressure, morphologic changes, mRNA and protein expressions of voltage-gated potassium channels (Kv1.5 channel), were measured. The concentrations of monocyte chemo-attractant protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-β1) were detected. Furthermore, pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured with or without hypoxia pretreated with or without 5-HD or/and Kv1.5 inhibitor 4-aminopyridine (4-AP). Mitochondrial membrane potential (Δψm) and the proliferation of PASMCs were detected.
  
  
  RESULTS
  5-HD significantly prevented the development of PAH by blocking the mitochondrial membrane depolarization, increased the expression of voltage-gated potassium channels, and reduced pulmonary hypertension mediated by TGF-β1 or MCP-1 signaling pathway.
  
  
  CONCLUSIONS
  The MitoKATP plays an important role in the development of PAH and may be therapeutic target for the treatment of disease.
authors: Li
authors: L
authors: Dong
authors: Yuping
authors: Y
authors: Li
authors: HongLing
authors: H
authors: Hu
authors: Lin
authors: L
authors: Shi
authors: Junjie
authors: J
authors: Chen
authors: Beibei
authors: B
authors: Wang
authors: Chaolei
authors: C
authors: Chen
authors: Haiping
authors: H
authors: Zhu
authors: Yunlei
authors: Y
authors: Li
authors: Qiu
authors: Q
authors: Li
authors: Liping
authors: L
authors: Zhang
authors: Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, China. chenchengshui@126.com.
authors: Chengshui
authors: C
authors: Chen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006880:Hydroxy Acids / Q000494:pharmacology / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D003652:Decanoic Acids; D006880:Hydroxy Acids; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid