title: [Pulmonary vascular remodeling and protein kinase C-alpha expression in chronic smoke exposure and/or hypoxia rats].
abstract: OBJECTIVE
  To investigate pulmonary vascular remodeling and protein kinase C-alpha (PKC-alpha) expression in chronic smoke exposure and/or hypoxia rats.
  
  
  METHODS
  Fifty-six male Wistar rats were randomly divided into seven groups: control group (C group), smoke exposure groups (S(4W), S(8W) group), hypoxia groups (H(4W), H(8W) group), smoke exposure plus hypoxia groups (SH(4W), SH(8W) group). Wistar rats were exposed to cigarette smoke and/or hypoxia air [O2 (10.0 +/- 0.5)%] for 4 to 8 weeks. A method by right cardiac catheterization was used for measuring mean pulmonary artery pressure (mPAP). Right ventricle (RV), left ventricle (LV) plus interventricular septum (S) were split and weighed and right ventricular hypertrophy index (RVHI) was calculated. To evaluate vascular remodeling, alpha-smooth muscle actin (alpha-SM-actin) staining and count of the percentage of muscularized small pulmonary arteries which was determined by morphometric analysis of histological sections were used. Pulmonary artery smooth muscle cell (PASMC) apoptosis was detected by in situ end labeling technique (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot analysis were used for the detection of PKC-alpha mRNA and protein expression in pulmonary arteries.
  
  
  RESULTS
  mPAP in H(4W), H(8W), SH(4W), SH(8W) group [(31 +/- 7), (32 +/- 8), (32 +/- 9), (31 +/- 10) mm Hg, 1 mm Hg = 0.133 kPa] were higher than that in C group [(14 +/- 4) mm Hg, all P < 0.01], but mPAP in S(4W) and S(8W) group [(15 +/- 5), (16 +/- 6) mm Hg] were not increased (all P > 0.05). In S(4W), S(8W), H(4W), H(8W), SH(4W) and SH(8W) group, RVHI (0.258 +/- 0.024, 0.394 +/- 0.021, 0.374 +/- 0.020, 0.414 +/- 0.019, 0.434 +/- 0.023, 0.442 +/- 0.020, respectively), the percentage of muscularized arteries [(33.5 +/- 6.8)%, (41.1 +/- 9.8)%, (35.9 +/- 6.6)%, (46.0 +/- 6.3)%, (42.9 +/- 6.5)%, (50.2 +/- 9.9)%, respectively] and alpha-SM-actin expression (53 +/- 15, 75 +/- 14, 56 +/- 11, 82 +/- 17, 83 +/- 17, 98 +/- 16, respectively) were increased significantly (all P < 0.01). PASMC apoptosis was increased and proliferation was markedly increased. Apoptotic indices (AI, 2.5 +/- 1.0, 3.8 +/- 1.4, 2.3 +/- 1.1, 3.3 +/- 1.1, 3.5 +/- 1.4, 4.8 +/- 1.4, respectively) and proliferation indices (PI, 33.1 +/- 11.8, 43.8 +/- 11.0, 36.5 +/- 10.6, 46.3 +/- 12.1, 45.3 +/- 12.4, 53.3 +/- 13.4, respectively) were higher than those in C group (all P < 0.01). The expressions of PKC-alpha mRNA and protein were higher than those of C group (all P < 0.01). The differences were more significant between SH(4W) and H(4W) group, SH(8W) and H(8W) group (all P < 0.01).
  
  
  CONCLUSIONS
  It is suggested that smoke is synergistic with hypoxia in aggravating pulmonary vascular remodeling. The possible mechanism is through PKC signaling transduction pathway activation.
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhao-xia
authors.initials: ZX
authors.lastname: Zhu
authors.forename: Yong-jian
authors.initials: YJ
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.forename: Zhen-xiang
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Wang
authors.initials: W
authors.lastname: Ni
authors.forename: Shi-Xin
authors.initials: SX
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004781:Environmental Exposure; D000860:Hypoxia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects
chemical_list: D012906:Smoke; D051571:Protein Kinase C-alpha