Proliferation Versus Apoptosis Activities Of Pulmonary Artery Smooth Muscle Cells In Pulmonary Arterial Hypertension Secondary To Chronic Obstructive Pulmonary Disease

Objective : To investigate the proliferation versus apoptosis activities of pulmonary artery smooth muscle cells(PASMCs) in pulmonary arterial hypertension(PAH) secondary to chronic obstructive pulmonary disease(COPD) and pulmonary vascular structural remodeling.Methods : Lung specimens from patients without COPD or PAH(non-COPD group, n=15), COPD patients without PAH(COPD non-PAH group, n=15)and patients with PAH secondary to COPD(COPD and PAH group, n=15) were investigated. The remodeling of pulmonary arteries were observed under microscope and the changes of morphology were analysed by computer-based image analysis system. The proliferation of PASMCs was detected by proliferating cell nuclear antigen (PCNA) with immunohistochemical technique, and TUNEL (Terminal deoxynucleotidyl transferase (TdT)- mediated deoxyuridine triphosphate (dUTP)- digoxigenin nick end labeling) technique was used for the detection of the apoptosis of PASMCs.Results : In non-COPD group, the walls of the pulmonary arterioles were thin and the lumens were large. In COPD non-PAH group, the walls were thicker and the lumens were narrower than that of the non-COPD group . In COPD and PAH group, the walls were the thickest and the lumens were the nanowest of the three groups. Both 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 calculated by the computer-based image analysis system. In the COPD non-PAH group and the COPD and PAH group, the WT% and WA% [ (20.45±4.12, 35.35±5.32) %, (28.47±4.67, 50.33±6.47) %] were higher than those of the non-COPD group (15.72±3.02, 24.73±3.32) % (P<0.01), and the WT% and WA% of the COPD and PAH group were higher than those of the COPD non-PAH group (P<0.01) . Both proliferative and apoptotic PASMCs were found in the patients of the three groups. The proliferation indexes (PI) of the COPD non-PAH group and the COPD and PAH group were (18.65 ±4. 82) %and (38.37 ±6.61) % respectively ,both were significantly higher than that of non-COPD group (8.37±2.09) % ( P<0.01). while the apoptosis indexes(AI) [ (4.49±1.25) %, (3.05 ±1.34) %] were lower than that of non-COPD group (6.90±1.89) % ( P<0.01). The proliferation index (PI) of the COPD non-PAH group was lower than that of the COPD and PAH group while the apoptosis index (AI)was higher than that of the COPD and PAH group ( P<0.05). The oxygen tension in arterial blood(PaO₂) of the COPD non-PAH group and the COPD and PAH group were (78.60±5.63) mmHg and (67.93±4.85) mmHg respectively ,both were significantly lower than that of non-COPD group(85.93±4.76)mmHg (P<0.01) , the PaO₂ of COPD and PAH group was lower than that of the COPD non-PAH group (P<0.01) .The PaO₂ of COPDnon-PAH group and the COPD and PAH group was negatively related with the PI(r=-0.519, P=0.003) while positively related to the AI of the PASMCs (r=0.441, P=0.015) .Conclusion : The imbalance of the increased proliferation and decreased apoptosis of PASMCs 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 PASMCs.