Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea

Zakrzewski, Maciej; Zakrzewska, Ewelina; Kiciński, Paweł; Przybylska-Kuć, Sylwia; Dybała, Andrzej; Myśliński, Wojciech; Pastryk, Jolanta Elżbieta; Tomaszewski, Tomasz; Mosiewicz, Jerzy

doi:10.1371/journal.pone.0166725

Cited by 23 publications

(16 citation statements)

References 34 publications

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“…Obstructive sleep apnoea is associated with heightened systemic inflammation, theoretically contributing to higher uPAR expression [11,[13][14][15]. However, the cleavage of uPAR may be slower in OSA due to decreased levels of uPA [8] and plasmin [5,6,23]. The expression of uPA is induced by female sexual hormones [20] and the proto-oncogenic survivin [27], which presented decreased expressions in OSA [3,28].…”

Section: Discussionmentioning

confidence: 99%

“…The expression of uPA is induced by female sexual hormones [20] and the proto-oncogenic survivin [27], which presented decreased expressions in OSA [3,28]. Plasmin is formed by plasminogen, and this reaction is blocked by plasminogen activator-inhibitors (PAI), shown to be upregulated in OSA [5,6,23]. In addition, OSA is associated with decreased levels of transforming growth factor-β [8], an inducer of uPAR transcription [29,30].…”

Section: Discussionmentioning

confidence: 99%

“…Chronic intermittent hypoxia and increased sympathetic tone induce production of pro-inflammatory molecules, such as interleukin (IL)-6, IL-1β, tumour necrosis factor-α [1] or complement elements [2] and suppresses the release of anti-inflammatory [3,4] molecules. Linked to inflammation and sympathetic activity, OSA is characterised by a hypercoagulation state [5][6][7][8][9]. Accelerated systemic inflammation and increased coagulation may contribute to the development of cardiovascular disease and acute cardiovascular events [10].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…In OSA children, PAI-1 levels were significantly higher along with other inflammatory markers such as IL-6 and monocyte chemoattractant protein-1 (MCP-1) [ 169 ]. A recent study has shown that OSA patients had a higher median plasma PAI-1 level than controls and PAI-1 levels increased with OSA severity, suggesting that OSA could enhance prothrombotic activity [ 170 ]. OSA significantly correlated with PAI-1 concentration due to prothrombotic effects.…”

Section: Complex Connections Among Osa Dpn and T2dmentioning

confidence: 99%

Interactions between and Shared Molecular Mechanisms of Diabetic Peripheral Neuropathy and Obstructive Sleep Apnea in Type 2 Diabetes Patients

Shen

Zhao

Liu

et al. 2018

Journal of Diabetes Research

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Type 2 diabetes (T2D) accounts for about 90% of all diabetes patients and incurs a heavy global public health burden. Up to 50% of T2D patients will eventually develop neuropathy as T2D progresses. Diabetic peripheral neuropathy (DPN) is a common diabetic complication and one of the main causes of increased morbidity and mortality of T2D patients. Obstructive sleep apnea (OSA) affects over 15% of the general population and is associated with a higher prevalence of T2D. Growing evidence also indicates that OSA is highly prevalent in T2D patients probably due to diabetic peripheral neuropathy. However, the interrelations among diabetic peripheral neuropathy, OSA, and T2D hitherto have not been clearly elucidated. Numerous molecular mechanisms have been documented that underlie diabetic peripheral neuropathy and OSA, including oxidative stress, inflammation, endothelin-1, vascular endothelial growth factor (VEGF), accumulation of advanced glycation end products, protein kinase C (PKC) signaling, poly ADP ribose polymerase (PARP), nitrosative stress, plasminogen activator inhibitor-1, and vitamin D deficiency. In this review, we seek to illuminate the relationships among T2D, diabetic peripheral neuropathy, and OSA and how they interact with one another. In addition, we summarize and explain the shared molecular mechanisms involved in diabetic peripheral neuropathy and OSA for further mechanistic investigations and novel therapeutic strategies for attenuating and preventing the development and progression of diabetic peripheral neuropathy and OSA in T2D.

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“…Clearly, these studies signify the physiological role of α2AP in vascular remodeling. Lately, subjects suffering from obstructive sleep apnea have also been shown with increased α2AP in plasma 16 . All these studies intrigued us to assess the effects of hypobaric hypoxia environment on alpha-2-antiplasmin expression and to evaluate its correlation to pulmonary hemodynamics.…”

Section: Introductionmentioning

confidence: 99%

Alpha-2-Antiplasmin : A Fibrinolytic Peptide, could be a Potential Biomarker for Diagnosis of High Altitude Induced Pulmonary Hypertension

Reddy

Malik

2017

Def. Sc. Jl.

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Prolonged exposure to high altitude is known to cause pulmonary vascular remodeling and pulmonary hypertension. Despite the advancements in diagnostics of pulmonary hypertension (PH), a potential biomarker for early diagnosis of PH progression is still lacking. High altitude induced pulmonary hypertension (HAPH) is great concern in mountain regions across the world. Early diagnosis and monitoring the disease progression are critical for therapeutic decisions. A fibrinolytic peptide, alpha-2-antiplasmin (α2AP) is known to cause tissue and vascular remodeling. Recently, elevated levels of α2AP were reported in different forms of PH; however its role in high altitude induced pulmonary hypertension is not yet known. To assess whether α-2AP can be used as diagnostic marker for HAPH, a cross sectional study was carried out on 100 healthy male Indian army soldiers who were posted to high altitude (14,800 ft to 18,700 ft) for a prolonged period of 6 to 8 months. We used 2D Echocardiography to screen the pulmonary arterial systolic pressure (PASP) and semi-quantitatively ELISA method for estimation of α-2AP in plasma. We found 34 out of 100 subjects have elevated PASP upon immediate screening after de-induction to moderate altitude of 10,000 ft. Age matched 17 subjects with elevated PASP were assessed for plasma levels of α-2AP in comparison to subjects with normal PASP, but posted to same altitude for same duration of time. Here for the first time we demonstrated an increase in plasma level of α-2AP was positively correlated with hypoxia induced elevated pulmonary arterial pressure. However, additional comprehensive investigations are warranted with large sample size to confirm our findings and explore the use of α2AP as potential diagnostic marker for monitoring progression of HAPH.

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Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea

Cited by 23 publications

References 34 publications

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

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

Interactions between and Shared Molecular Mechanisms of Diabetic Peripheral Neuropathy and Obstructive Sleep Apnea in Type 2 Diabetes Patients

Alpha-2-Antiplasmin : A Fibrinolytic Peptide, could be a Potential Biomarker for Diagnosis of High Altitude Induced Pulmonary Hypertension

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