Pulmonary vascular remodeling is prior to the increase in pulmonary hypertension of chronic obstructive pulmonary disease

Abstract

Objective: To explore the remodeling of pulmonary arterioles in chronic obstructive pulmonary disease (COPD), and its effect on hemorheology of proximal pulmonary arteries, right ventricular structure and function , and the potential mechanisms. Method: A total of 34 patients undergoing surgical treatment for lung tumors admitted to the General Hospital of Ningxia Medical University were included in the study. According to the preoperative lung function, there were 15 patients with COPD complicated with lung tumor (COPD group) and 19 patients with normal pulmonary function with lung tumor (control group). All patients underwent cardiac nuclear magnetic resonance (CMR) before surgery, and the hemorheology of the proximal pulmonary arteries, right ventricular structure and function were obtained by CMR. The normal lung tissues distal to the tumor lesion were taken during the operation, and the morphological changes of the pulmonary arterioles were observed by hematoxylin-eosin staining and Weigert-van Gieson. Immunohistochemistry was used to detect the location and expression of α-smooth muscle actin(SMA) and proliferating cell nuclear antigen(PCNA) in pulmonary arterioles, and the expression of protein and mRNA of α-SMA in lung tissue was detected by Western-blotting and real-time quantitative PCR. Results: The results of CMR showed that mPAP was not statistically different between COPD group and control group (24.0±3.7 vs 22.8±1.6, P>0.05). The main pulmonary artery distensibility (mPAD%), right ventricular myocardial mass end-diastolic (RVMED), right ventricular myocardial mass end-systolic (RVMES), average negative flow(ANF) and regurgitant fraction(RF%) were statistically different between COPD group and control group (P<0.05). The wall thickness (WT), WT% and WA% were significantly higher in COPD group [(37±18) μm, (65±19)% and (55±23)%, respectively] than in control group [(19±3 )μm, (29±5)% and (40±7)%, respectively]. The number of pulmonary arterial smooth muscle cells per unit area and smooth muscle cell proliferation rate were significantly higher in COPD group than in the control group(P<0.01). The expression of α-SMA protein and mRNA in COPD group was higher than that in control group(P<0.05). WA% and WT% were correlated inversely with mPAD%, but positively with RVMES, RVMED and RF%. Conclusions: Pulmonary vascular remodeling and rheological changes, even right heart myocardial structural changes, were observed in COPD patients without pulmonary arterial hypertension. Pulmonary arteriolar remodeling can affect the main pulmonary arterial hemorheology in COPD patients and further affect the myocardial structure of right heart. Pulmonary arterial remodeling may be a new direction for the clinical treatment of COPD.