The Expression And Clinical Significance Of VEGF And ET-1 In Pulmonary Arteries Of Patients With Pulmonary Arterial Hypertension Secondary To Chronic Obstructive Pulmonary Disease

Objective: To investigate the expression of VEGF and ET-1 in pulmonary artery smooth muscle cells(PASMCs) in pulmonary arteries of patients with pulmonary arterial hypertension(PAH) secondary to chronic obstructive pulmonary disease(COPD), and therefore to explore the possible roles of VEGF and ET-1 in the development of PAH secondary to COPD.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. Haematoxylin-eosin(HE)staining was performed and pathological image analysis software was used to determine pulmonary arterial wall area/total vascular area(WA%), lumina area/total vascular area(LA%), smooth muscle cell density(SMC) in the media of pulmonary arteriole and pulmonary artery media thickness(PAMT), which were used as remodeling indexes of pulmonary arteriole. The immunohistochemistry was used to observe the expression of VEGF and ET-1 in pulmonary artery smooth muscle cells.Result: In non-COPD group, the walls of the pulmonary arterioles were thin and the lumens were regular. In COPD non-PAH group, the pulmonary arteriole wall was thickened, lumens became narrowed and the number of smooth muscle cells in the intima-media of pulmonary arteriole was increased. In COPD and PAH group, the walls were the thickest and the lumens were the narrowest of the three groups and obvious smooth muscle hyperplasy was found. Morphometry analysis showed that the ratio of small pulmonary arteriole lumina area to total vascular area(LA%) decreased respectively(64.7±3. 6, 55.1±2. 8, 42. 4±3. 9)% and the ratio of the wall area to total vascular area(WA%) increased respectively(29.1±4. 6, 39.2±3.9, 55.2±5. 8)% in non-COPD group, COPD non-PAH group and COPD and PAH group, when compared each other there were significant differences in three group(P<0.01, respectively). SMC and PAMT both showed a sequence of non-COPD group < COPD non-PAH group < COPD and PAH group, when compared each other there were significant differences in three group (P<0.01, respectively). The expression of VEGF and ET-1 in pulmonary artery smooth muscle cells of the COPD non-PAH group and the COPD and PAH group were higher than those of the non-COPD group (all P<0.01). The expression of VEGF and ET-1 in pulmonary artery smooth muscle cells of the COPD and PAH group were higher than those of the COPD non-PAH group (both P<0.01).In three group the increment of expression of VEGF and ET-1 were negatively correlated with LA% (r= - 0.652, - 0.588, both P <0.001) and positive correlated with WA%,SMC and PAMT (r=0.593～0.691, all P<0.001). In three group the PASP were negatively correlated with LA% (r= - 0.491, P <0.001) and positive correlated with WA%,SMC and PAMT (r=0.539, 0.484, 0.510, all P<0.001), and the increment of expression of VEGF and ET-1 were positive correlated (r=0.891, P <0.001).Conclusion: There were higher expression of VEGF and ET-1 in pulmonary artery smooth muscle cells in pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease. The VEGF and ET-1 may play an important role in the pathogenesis progress of hypoxic pulmonary vascular remodeling and pulmonary hypertension.