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

Abstract

BackgroundPlasminogen 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.MethodsDemographic 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.ResultsFirst, 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 (FEV1/FVC), FEV1/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV3/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 FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1.ConclusionOur 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.

Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

“…Interestingly, this study found the highest PAI-1 levels in patients with GOLD Stages II and III. This observation is in good agreement with the finding of the previous study showing a significant association between higher levels of PAI-1 and airflow limitation in patients with predominantly mild-to-moderate COPD 15. Moreover, it was also found that triglycerides and hs-CRP are the best predictors for elevated PAI-1 levels in COPD patients.…”

“…There are two very recent studies showing an association between elevated PAI-1 levels and COPD, but considered neither comorbidities of COPD nor the whole spectrum of airflow limitation, from mild to very severe stage 14,15. The present study is the first to demonstrate that higher serum PAI-1 levels in COPD are independent of a broad spectrum of possible confounders, in particular established variables indicating metabolic and cardiovascular dysfunction.…”

“…Indeed, a recent case–control study demonstrated that PAI-1 polymorphisms related to a higher PAI-1 expression are associated with COPD 14. Furthermore, a study conducted on patients with predominantly mild-to-moderate COPD found that higher serum PAI-1 levels are related to airflow limitation 15. Whether the observed elevation in PAI-1 levels in COPD is independent of metabolic and cardiovascular functions is unknown.…”

Soluble Urokinase-Type Plasminogen Activator Receptor and Arterial Stiffness in Patients with COPD

“…In stable disease, Can et al reported higher serum suPAR levels compared to controls [ 14 ]. This contradicts a study by Wang et al who did not find significant difference between COPD and those in a healthy condition [ 15 ]. The discrepancy may be due to the relatively mild disease severity of the latter study [ 15 ], as the former study assessed patients with a wider range of lung function [ 14 ].…”

“…This contradicts a study by Wang et al who did not find significant difference between COPD and those in a healthy condition [ 15 ]. The discrepancy may be due to the relatively mild disease severity of the latter study [ 15 ], as the former study assessed patients with a wider range of lung function [ 14 ]. In addition, a number of factors which characterize disease burden apart from lung function, including symptom burden, exacerbation history and arterial stiffness, has not been assessed.…”