[Apoptosis versus proliferation activities of pulmonary artery smooth muscle cells in pulmonary arterial hypertension associated with chronic obstructive pulmonary disease].
OBJECTIVE
To investigate the apoptosis versus proliferation activities of pulmonary artery smooth muscle cells (PASMC) in pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD) and pulmonary vascular structural remodeling.


METHODS
Forty-five patients were divided into three groups: patients without COPD and PH (non-COPD group, n = 15), COPD patients without PH (COPD with non-PH group, n = 15) and patients with PH associated with COPD (COPD with PH group, n = 15). Lung tissue samples were obtained from surgically resected specimens. The remodeling of pulmonary arteries were observed under microscope, and the changes of morphology-the ratio of the thickness of the wall to the external diameter of the pulmonary arterioles (WT%) and the ratio of the area of the wall to that of the pulmonary arterioles (WA%) were analyzed by computer-based image analysis system. The proliferation of PASMC was detected by proliferating cell nuclear antigen (PCNA) with immunohistochemical technique, and TUNEL (terminal deoxynu-cleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling) was used for the detection of the apoptosis of PASMC.


RESULTS
In the COPD with non-PH group, the arterial walls were thicker and the lumens narrower than that of the non-COPD group. In the COPD with PH group, the walls were thicker and the lumens narrower than that of the COPD with non-PH group. In the COPD with non-PH group and the COPD with PH group, the WT% and WA% [(20 +/- 4)% and (35 +/- 5)%; (28 +/- 5)% and (50 +/- 6)%, respectively] were higher than those of the non-COPD group (16 +/- 3)% and (25 +/- 3)% (P < 0.01), and the WT% and WA% of the COPD with PH group were higher than those of the COPD with non-PH group (P < 0.01). Both proliferative and apoptotic PASMC were found in the patients of the three groups. The proliferation indexes (PI) of the COPD with non-PH group and the COPD with PH group [(19 +/- 5)% and (38 +/- 7)%] were significantly higher than that of the non-COPD group [(8 +/- 2)%, P < 0.01], while the apoptosis indexes (AI) [(4.5 +/- 1.3)% and (3.1 +/- 1.3)%] were lower than that of the non-COPD group [(6.9 +/- 1.9)%, P < 0. 01]. The PI of the COPD with non-PH group was lower than that of the COPD with PH group; the AI was higher than that of the COPD with PH group (P < 0.05). The PaO(2) of the COPD with non-PH group and the COPD with PH group was negatively related with the PI (r = -0.519, P = 0.003), but positively related to the AI of the PASMC (r = 0.441, P = 0.015).


CONCLUSIONS
The imbalance of the increased proliferation and decreased apoptosis of PASMC may contribute to the pulmonary vascular structural remodeling and pulmonary arterial hypertension in patients of COPD. Hypoxia is one of the main causes of increased proliferation and decreased apoptosis of the PASMC.
Yu
Wen-Cheng
WC
Department of Respiratory, Medical School Hospital of Qingdao University, Qingdao 266003, China.
Guo
Cai-Hong
CH
D000368:Aged; D017209:Apoptosis; D049109:Cell Proliferation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology / Q000503:physiopathology*