Serum Endostatin Is a Novel Marker for COPD Associated with Lower Lung Function, Exacerbation and Systemic Inflammation

Abstract

Backgrounds and aims: It is well known that angiogenesis contributes to the progression of chronic obstructive pulmonary disease (COPD) by initiating the remodeling of bronchial vasculature. However, the specific molecular mechanisms are incompletely understood. This research aimed to explore whether endostatin, a member of endogenous antiangiogenic proteins, is a biomarker in COPD and plays a role in the angiogenesis of COPD.

Methods: 100 stable COPD patients, 130 patients with acute exacerbation (AECOPD) and 68 healthy volunteers were recruited in this research. Lung function test was conducted in the healthy people and stable COPD patients. Serum endostatin, C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) of all the subjects were measured by Human Magnetic Luminex Screening Assay.

Results: Serum endostatin level was significantly higher in stable COPD compared with healthy control and even more in AECOPD patients (P<0.001). Besides, stable COPD patients with frequent exacerbation (≥2 exacerbations per year) in the last 1 year had a higher concentration of endostatin in the circulation compared to the patients with less exacerbation (P=0.037). Furthermore, circulatory endostatin was negatively associated with forced expiratory volume in 1 s % predicted (FEV₁%pre), an index of lung function in the stable COPD group (P=0.009). Finally, endostatin was positively correlated to serum CRP in COPD group (including stable and AECOPD) (P=0.005) and all the subjects (P<0.001), but only associated with VEGF in the total participants (P=0.002), not in the COPD group.

Conclusion: These results suggested that endostatin is a biomarker for COPD and associated with lower lung function, exacerbation, and systemic inflammation. Endostatin potentially contributes to the pathogenesis of COPD.

Keywords: angiogenesis; chronic obstructive pulmonary disease; endostatin; inflammation; lung function.

Figure 1

Comparison of serum endostatin levels among different groups. Serum endostatin levels showed an upward trend in COPD patients (A, B); differences of endostatin levels between ever-smoking and never smoking were observed in stable COPD group but not in the healthy control group (C). Abbreviations: HC, healthy control; COPD, chronic obstructive pulmonary disease; AECOPD, COPD with acute exacerbation; GOLD, Global Initiative for Chronic Obstructive Lung Disease.

Figure 2

Comparison of serum endostatin and CRP between different stable COPD patients. Circulating endostatin (A) and CRP (B) were significantly higher in the FE group compared to the non-FE group. Abbreviations: FE, frequently exacerbation; CRP, C-reactive protein.

Figure 3

Serum endostatin was correlated with pulmonary function. Serum endostatin was inversely correlated with (A) FEV₁/FVC and (B) FEV₁%pre. After adjusting age, BMI, sex and smoking status, endostatin level was still inversely associated with FEV₁%pre in the stable COPD group (C) and in the total of healthy control and stable COPD (D). The red solid line denotes the line of best fit in stable COPD, the black line represents the line of best fit in a total of healthy control and stable COPD. Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity.

Figure 4

Correlation analyses between serum endostatin levels and other COPD biomarkers. Serum endostatin was positively correlated to serum CRP (A) and VEGF (B). After adjusting age, BMI, sex and smoking status, endostatin was positively associated with CRP (C) and VEGF (D) in all the participants. The blue solid line denotes the line of best fit in COPD, the black line represents the line of best fit in all the participants. Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; VEGF, vascular endothelial growth factor.

Figure 5

Diagnostic value of endostatin for COPD.