Objective: To study the expression of hypoxia-inducible factor (HIF)-1α in lung tissues and sera from chronic obstructive pulmonary disease (COPD) patients and smokers with normal lung function and explore its clinical significance.
Methods: Lung tissue samples were obtained from 32 patients undergoing surgery for peripheral lung tumors. Lung function test was performed before lung cancer surgery. Based on lung function and smoking status, 32 patients were devided into three groups: smokers with stable COPD (COPD group, n=10), smokers with normal lung function (S group, n=10) and nonsmokers with nomal lung function (NS group, n=10). The preoperative fasting sera and lung tissues as far as possible away from the tumor site from all patients were collected. HIF-1α levels in sera and lung tissue homogenates were evaluated by ELISA. The expression of HIF-1α in airway epithelium, alveolar wall and blood vessel wall were detected by immunohistochemistry. Furthermore, the correlation between HIF-1α expression levels and pulmonary function was analyzed.
Results: Serum HIF-1α levels were significantly elevated in COPD group [(73.25 ± 6.12) pg/mL] and S group [(60.30 ± 8.00) pg/mL] as compared with NS group [(47.03 ± 8.43) pg/mL, P<0.01], and COPD group was significantly higher than S group (P<0.01). The concentrations of HIF-1α in lung tissue homogenates significantly increased in COPD group [(2.04 ± 0.24) pg/μg] and S group [(1.67 ± 0.34) pg/μg] as compared with NS group [(1.12 ± 0.33) pg/μg, P<0.01], and COPD group was also significantly higher than S group (P<0.01). HIF-1α expression was located in inflammatory cells and macrophages of airway epithelium, alveolar wall and small pulmonary artery wall. HIF-1α levels in sera and lung tissue homogenates showed negative correlations with FEV1/FVC and FEV1% predicted.
Conclusion: HIF-1α levels are raised in sera and lung tissues of COPD patients and smokers with normal lung function, and they were positively correlated with the severity of airflow limitation.