Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

Abstract

Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.Medicina 2020, 56, 77 2 of 10 Soluble urokinase-type plasminogen activator receptor (suPAR) is a molecule which plays a role in both inflammation and coagulation. It is produced upon cleavage of the membrane-bound urokinase-type plasminogen activator receptor (uPAR). The cleavage is facilitated by urokinase-type plasminogen activator (uPA), plasmin, matrix metalloproteases, neutrophil elastase and cathepsin G [11]. The urokinase receptor (also known as uPAR) is expressed by endothelial cells, macrophages, monocytes, neutrophils, lymphocytes, smooth muscle cells and fibroblasts [12,13]. It is upregulated under infections and as an effect of pro-inflammatory cytokines [11,[13][14][15], while suPAR contributes to plasminogen activation, cell adhesion, chemotaxis and immune cell activation [16]. However, uPAR also acts as a scavenger receptor for uPA, inhibiting its actions [17]. In large studies, plasma suPAR was elevated in coronary artery disease and cerebrovascular disease and correlated with their severity and cardiovascular mortality [18][19][20]. Higher suPAR levels were also observed in obesity [21], which is the main etiological factor for OSA in the Western population [22].Only one study has investigated suPAR in probable OSA so far [23]. Patients were categorised to high and low-risk OSA based on the Berlin questionnaire and neck circumferences; however, no objective sleep tests were performed. In this study, there was a tendency for higher suPAR levels in the high-risk group, but...

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