title: [Hypoxia induced the remodeling of pulmonary vein smooth muscle and reduced peroxisome proliferator activated receptor γ expression].
abstract: OBJECTIVE
  To investigate the effect of chronic hypoxia on pulmonary vein remodeling in rats and its underlying molecular mechanism.
  
  
  METHODS
  Totally 20 adult SD rats (200-250 g), in accordance with a random number table, were divided into normoxia control group (NC) and chronic hypoxia group (CH). CH group rats were put into automatic hypoxia box for 21 days. After that, RVSP, mRVP and RV/( LV+S) were measured; Lung histopathological sections were prepared. The lumen area, ratio of wall thickness to radius of pulmonary veins were gauged by using the Image Pro Plus 6.0 software. Primary PVSMCs were cultured in hypoxia (4% O₂) or normoxia (21% O₂) for 60 hours respectively before extracted total protein for Western blotting analysis. PPARγ protein expression in rat pulmonary vein smooth muscle and pulmonary vein smooth muscle cells was detected by Western blot.
  
  
  RESULTS
  Compared with NC group [(27.06 ± 2.10), (12.58 ± 0.82) mmHg (1 mmHg=0.133 kPa)], the RVSP and mRVP in CH group [(50.46 ± 9.51), (21.66 ± 1.85)mmHg] were significantly increased (P<0.05). The RV/(LV+S) of CH group was (0.56 ± 0.05), markedly higher than that of NC group (0.36 ± 0.04, P<0.05). The luminal area/total area of vein in CH group decreased to (48.62 ± 13.61)% compared with that in NC group (66.16 ± 8.72)% (P<0.05). The wall thickness/venous radius (WT%) of CH group increased from (7.23 ± 0.71)% (NC) to (16.43 ± 5.08)% (P<0.05). The level of PPARγ protein in pulmonary vein smooth muscle of CH group was (52.95 ± 3.83)%, lower than that of NC (100 ± 0)% (P<0.05). PPARγ protein in pulmonary vein smooth muscle cells cultured in vitro in hypoxia was (59.38 ± 17.12)%, lower than that cultured in normoxia (100 ± 0)% (P<0.05).
  
  
  CONCLUSIONS
  Hypoxia induced increase of RVSP, mRVP, RV/(LV+S), and accompanied with pulmonary venous remodeling. The underlying mechanism of the vein change may related to down-regulated expression of PPARγ.
authors.affiliation: Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Lu
authors.affiliation: Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Diseases, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China; Email: jianwang1986@yahoo.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D006976:Hypertension, Pulmonary; D000860:Hypoxia; D008168:Lung; D032389:Myocytes, Smooth Muscle; D047495:PPAR gamma; D011667:Pulmonary Veins; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047495:PPAR gamma