title: Activation of PPAR-γ ameliorates pulmonary arterial hypertension via inducing heme oxygenase-1 and p21(WAF1): an in vivo study in rats.
abstract: OBJECTIVE
  Our previous study has indicated that activation of PPAR-γ inhibits the proliferation of rat pulmonary artery smooth muscle cells (PASMCs) in vitro through inducing the expression of heme oxygenase-1 (HO-1), which in turn up-regulates the p21(WAF1) expression. In the present study, we intended to determine whether similar mechanisms have been involved in activation of PPAR-γ inhibition of development of rat PAH model.
  
  
  METHODS
  Rat pulmonary arterial hypertension (PAH) model was established by subcutaneous injection of monocrotaline (MCT). Rosiglitazone was administered to activate PPAR-γ. Zinc protoporphyria IX (ZnPP-IX), was used to confirm the role of HO-1 in mediating PPAR-γ function. Parameters including the right ventricle systolic pressure (RVSP), the right ventricular hypertrophy (RVH) and the percentage of medial wall thickness were used to evaluate the development of PAH. Immunoblotting was used to determine the expression of HO-1 and p21(WAF1).
  
  
  RESULTS
  Rosiglitazone significantly decreased the RVSP and inhibited the RVH in MCT-induced rat PAH model, and partially inhibited the pulmonary vascular remodeling. These effects were coupled with the sequential increase of HO-1 and p21(WAF1) expressions by rosiglitazone.
  
  
  CONCLUSIONS
  Activation of PPAR-γ benefits PAH by inhibiting proliferation of PASMCs and reducing pulmonary vascular remodeling. The present study suggests that enhancing PPAR-γ activity might have potential value in clinical treatment of PAH.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Guizuo
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, China. Electronic address: manxiangli@hotmail.com.
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D005786:Gene Expression Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051547:Heme Oxygenase-1
keywords: Heme oxygenase-1; Peroxisome proliferator-activated receptor-γ; Pulmonary arterial hypertension; Pulmonary vascular remodeling; p21(WAF1)