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

Yanqiu Wu,1,2 Jiangyue Qin,1,2 Junyun He,3 Yongchun Shen,1,2 Hao Wang,1,2 Yanping Li,4 Qianglin Zeng,5 Jiajia Dong,1,2 Yunfei An,6 Shuguang Xiong,7 Mei Feng,2 Fuqiang Wen1,2 1Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region, Chengdu, Sichuan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Third People’s Hospital of Chengdu, Sichuan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, People’s Republic of China; 6Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, 416 Hospital of Nuclear Industry, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Fuqiang WenDivision of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, People’s Republic of ChinaTel +86-28-8542 2350Email wenfuqiang@scu.edu.cnBackgrounds 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: chronic obstructive pulmonary disease, endostatin, lung function, angiogenesis, inflammation