title: Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery.
abstract: BACKGROUND
  The current study was performed to investigate the effect of adenosine monophosphate (AMP) - activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms.
  
  
  METHODS
  PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK. Immunoblotting was used to determine the phosphorylation and expression of AMPK and expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Gelatin zymography was performed to determine the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9.
  
  
  RESULTS
  Activation of AMPK by MET significantly reduced the right ventricle systolic pressure and the right ventricular hypertrophy in MCT-induced rat PAH model, and partially inhibited the ECM remodeling of pulmonary arteries. These effects were coupled with the decrease of MMP-2/9 activity and TIMP-1 expression.
  
  
  CONCLUSIONS
  This study suggests that activation of AMPK benefits PAH by inhibiting ECM remodeling of pulmonary arteries. Enhancing AMPK activity might have potential value in clinical treatment of PAH.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Shaojun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Xinming
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Rui
authors.initials: R
authors.lastname: Ke
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Yanting
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D016686:Monocrotaline / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D016686:Monocrotaline; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2