Objective: To study the relation between connective tissue growth factor (CTGF) expression of pulmonary arteries and pulmonary arteries remodeling in smokers and in chronic obstructive pulmonary disease (COPD) patients.
Methods: Pulmonary tissues removed for lung cancer from 24 patients were assigned into non-smoker control group (N), smoker group (S), smoker and COPD group (S + C), 8 subjects each group. The specimen were obtained far from the cancer focus (>5 cm). Pulmonary arterial remodeling was observed by hematoxylin-eosin staining, and collagen contents of pulmonary artery wall were measured by sirius red staining and picro-polarization method. Immunohistochemistry was used to determine the proliferating cell nuclear antigen (PCNA) and CTGF protein expression of pulmonary artery smooth muscles. The CTGF mRNA expressions of pulmonary arteries were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). The difference between the groups was analyzed.
Results: (1) The percent of pulmonary artery wall area to total area (WA%) of the three groups were (28.4 +/- 4.7)%, (46.3 +/- 3.5)% and (55.5 +/- 3.9)%, respectively. Compared to the control group, there was a significant increase in the S and the S + C groups (P < 0.01). (2) The collagen thickness of pulmonary arteries was (6.4 +/- 1.6) microm, (15.9 +/- 2.4) microm and (16.4 +/- 2.3) microm, respectively. Collagen was abnormally increased and deposited in pulmonary artery walls of the S and the S + C groups (P < 0.01). (3) CTGF mRNA expressions of pulmonary artery walls were 0.095 +/- 0.015, 0.396 +/- 0.167 and 0.501 +/- 0.177, respectively. Compared to the control group, there was a significant increase in the S and the S + C groups (P < 0.01). (4) PCNA expressions of pulmonary artery walls were 0.084 +/- 0.006, 0.178 +/- 0.018 and 0.226 +/- 0.134, respectively; the expressions of the S and the S + C groups were significant increased as compared to the control group (P < 0.01). (5)CTGF protein expressions of pulmonary artery walls were 0.085 +/- 0.011, 0.245 +/- 0.095 and 0.303 +/- 0.191, respectively; compared to the control group, there was a significant increase in the S and the S + C groups (P < 0.01). (6) Both CTGF mRNA and protein expression of pulmonary arteries were positively correlated with WA% (r = 0.915, P < 0.01; r = 0.919, P < 0.01). Similarly, both CTGF mRNA and protein expression of pulmonary arteries were positively correlated with PCNA expression (r = 0.938, P < 0.01; r = 0.928, P < 0.01).
Conclusion: Pulmonary artery remodeling is evident in smokers without COPD, but the remodeling became more severe in patients with COPD. Increased expression of CTGF may play an important role in pulmonary artery remodeling.