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

Abstract

IntroductionPlasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear.MethodsIn this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined.ResultsThe serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis.ConclusionThe data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations.

Association between serum adiponectin concentrations and chronic obstructive pulmonary disease: a meta-analysis

“…Our findings provide convincing evidence that serum concentrations of adiponectin were higher in COPD patients than in healthy controls. This result of the pooled analysis is in accordance with most findings of previous studies [15][16][17]19,20,[23][24][25]27]. Serum adiponectin levels correlated inversely with BMI in patients with COPD [20,22,23,27], which indicates that the adipose tissue may be an important influence factor to the serum adiponectin level in COPD.…”

“…Finally, 13 articles were included for this meta-analysis, containing 1131 COPD patients and 689 controls in total. The subjects of nine studies were stable COPD patients [15][16][17][18][19][20][21][22][23], three studies involved stable COPD patients and AECOPD patients [24][25][26], and one study involved mixed COPD patients [27]. In 12 studies [15][16][17][18][19][20][21][22][23][25][26][27], the control participants were matched for all the main confounders (BMI, age, gender) with the OSA patients.…”

Stroke risk among patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

“…In the current study, although the majority of stroke events among COPD patients were of the ischemic type, the association between COPD and the risk of hemorrhagic stroke was also robust. Levels of plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, were found to be higher in COPD patients and may contribute to thrombosis and ischemic stroke among these patients 37 . Plasminogen activators were found to be beneficial for patients with mild stroke 38 .…”

Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells

“…Collectively, these results reveal that Adp might play an important role in regulating the fibrinolytic system. In addition, elevated PAI-1 levels may be involved in obesity, metabolic syndrome, diabetes mellitus, thrombosis, endometriosis, atherosclerosis, cancer, and multiple organ fibrosis [21][22][23][24]; we predicated that Adp may be utilized as a novel agent in the treatment of these human diseases. However, to assess the effects of Adp on fibrinolytic balance, theexpressionlevels of t-PA, u-PA, and u-PA receptor (u-PAR) need to be examined because fibrinolysis is determined by a balance of inhibitors and activators.…”