Elevated circulating PAI-1 levels are related to lung function decline, systemic inflammation, and small airway obstruction in chronic obstructive pulmonary disease

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. METHODS: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers. Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay. Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test. Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD. RESULTS: First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007). Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV(1)/FVC), FEV(1)/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV(3)/FVC, MMEF25–75/Pre (justified r=−0.289, P=0.001; justified r=−0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively). Besides, multivariable linear analysis showed that FEV(1)/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1. CONCLUSION: Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD.