Diurnal variation of circulating microvesicles is associated with the severity of obstructive sleep apnoea

Bikov, András; Kunos, László; Pállinger, Éva; Lázár, Zsófia; Kis, Adrián; Horváth, Gábor; Losonczy, György; Komlósi, Zsolt István

doi:10.1007/s11325-017-1464-y

Cited by 20 publications

(23 citation statements)

References 31 publications

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“…Disrupted sleep is a major component in the pathophysiology of OSA. Still, the number of studies investigating inflammatory biomarkers before and after night is low (Bikov et al., ; Jordan et al., ; Kunos et al., ; Mills, Natarajan, Von Kanel, Ancoli‐Israel, & Dimsdale, ; Nobili et al., ). In contrast to the findings on CRP (Mills et al., ), we did not find an overnight change in C3a or SC5b‐9 in the OSA or control groups.…”

Section: Discussionmentioning

confidence: 99%

“…Polysomnography was performed as it was described previously (Bikov et al., ; Kunos et al., , ) using Somnoscreen Plus Tele PSG (Somnomedics GmbH Germany). Electroencephalogram, electrooculogram and electromyogram, thoracic and abdominal respiratory excursions, breath sounds, nasal airflow, electrocardiogram and oxygen saturation were recorded according to guidelines (Kushida et al., ).…”

Section: Methodsmentioning

confidence: 99%

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Complement system activation in obstructive sleep apnea

Horváth

Tárnoki

et al. 2018

Journal of Sleep Research

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The complement system may play a role in the systemic inflammation characterising obstructive sleep apnea; however, this has not been investigated before. We aimed to study the involvement of effector complement elements in obstructive sleep apnea, namely C3a, C5a and SC5b-9. Venous blood was collected in 50 patients with obstructive sleep apnea and 26 control subjects in the evening and the following morning. Plasma complement proteins were analysed with ELISA. Complement factor levels were compared between the two groups and correlated with clinical variables. Plasma C3a concentration was elevated in obstructive sleep apnea both in the evening (84.1 [0-338.5] ng ml ) and in the morning (85.5 [0-247.8] ng ml ) compared with controls (30.3 [0-176.8] ng ml and 36.3 [0-167.1] ng ml , evening and morning, respectively, both p < 0.05). On the contrary, C5a and SC5b-9 levels were comparable between patients and controls at each time point (p > 0.05). There was no change in complement factors from evening to morning in either group (p > 0.05), except for C5a that decreased from evening to morning in obstructive sleep apnea (from 11.6 [1.6-47.4] ng ml to 9.3 [0-46.4] ng ml , p = 0.01). Elevated C3a levels were directly related to obstructive sleep apnea severity, and were significantly associated with male gender, weight, body mass index, hypertension, high C-reactive protein and low high-density lipoprotein cholesterol (p < 0.05). The complement system is activated in obstructive sleep apnea, which is correlated with disease severity. Our findings highlight the potential role of complement system in the pathophysiology of obstructive sleep apnea, thus facilitating further research.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Complement system activation in obstructive sleep apnea

Horváth

Tárnoki

et al. 2018

Journal of Sleep Research

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“…These, together with hypoxia itself induce the expression of adhesion molecules, such as P-selectin. P-selectin is expressed upon stimulation by thrombin [3], hypoxia [4] or cytokines [5] by platelets and endothelial cells, however platelet P-selectin expression may be less important in OSA compared to endothelial P-selectin [6,7]. P-selectin enhances the adhesion between leukocytes and endothelial cells thus slowing down the rolling of leukocytes and facilitating their extravasation.…”

Section: Introductionmentioning

confidence: 99%

“…P-selectin enhances the adhesion between leukocytes and endothelial cells thus slowing down the rolling of leukocytes and facilitating their extravasation. P-selectin has extensively been investigated in OSA [6][7][8][9][10][11][12] with some studies reporting elevated blood P-selectin levels [8,11,12], but not all [6,7,10]. A potential explanation for the contradictory findings could be the presence of comorbid obesity, as one study reported no difference in circulating P-selectin levels between OSA and body mass index (BMI)-matched controls [6].…”

Section: Introductionmentioning

confidence: 99%

Circulating P-Selectin Glycoprotein Ligand 1 and P-Selectin Levels in Obstructive Sleep Apnea Patients

Horváth

Lázár

Gálffy

et al. 2020

Lung

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Purpose Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia which induces inflammation in blood vessels leading to the development of cardiovascular comorbidities. Several studies implicated the role of P-selectin in vascular inflammation of OSA. P-selectin glycoprotein ligand 1 (PSGL-1) is the main activator for P-selectin and is involved in immune cell trafficking. However, PSGL-1 has not been analyzed in OSA. The aim of the study was to investigate plasma PSGL-1 and P-selectin levels to have a deeper understanding on their interaction in obstructive sleep apnea. Methods Fifty-one untreated patients with OSA and 42 non-OSA controls were recruited. Plasma PSGL-1 levels were determined in evening and morning samples, P-selectin levels were analyzed in morning samples using commercially available ELISA kits. Polysomnography was performed in all participants. OSA was defined by an apnea-hypopnea index ≥ 5/h. Results PSGL-1 levels did not differ between controls and OSA patients either in the evening or in the morning. Although, there was no difference between controls (16.9/6.8-40.8 ng/ml) and patients with OSA (19.6/8.4-56.8, p = 0.24), patients with severe OSA had increased plasma P-selectin levels (25.6/8.4-56.8 ng/ml) compared to mild OSA patients (14.1/8.5-35.3 ng/ ml, p = 0.006) and controls (p = 0.03). Conclusions P-selectin expression relates to disease severity suggesting a pathophysiological role in endothelial cell activation. PSGL-1 levels are unaltered in OSA, suggesting an alternative activation pathway for P-selectin in OSA.

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“…Annexin V has been associated with endothelial dysfunction and is a predictor of cardiac events [76]. Endothelial dysfunction and increased serum levels of annexin V have been observed in OSA patients, and is exacerbated during sleep [77][78][79]. Annexin V is associated with increased prevalence of atrial natriuretic peptide granules and has been shown to concentrate around the Z-line in rat atria [80,81].…”

Section: Resultsmentioning

confidence: 99%

Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using twodimensional polyacrylamide gel electrophoresis and mass spectrometry

Lux

Channaveerappa

Aslebagh

et al. 2018

Preprint

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Obstructive sleep apnea (OSA) affects an estimated 20% of adults worldwide with up to 80% of patients remaining undiagnosed. OSA has been associated with electrical and structural abnormalities of the atria, although the molecular mechanisms are not well understood. We have implemented a rat model of OSA involving the surgical implantation of a tracheal obstructive device. Rats were divided into severe and moderate apnea groups, receiving 23 seconds (severe) or 13 seconds (moderate) apneas per minute, 60 apneas per minute for 8 hours a day over 2 weeks. We recently performed a pilot study using onedimensional polyacrylamide gel electrophoresis (1D PAGE) and nanoliquid chromatography-tandem mass spectrometry (NanoLC-MS/MS) to investigate the protein dysregulations in rat atria which was induced with OSA using the rat model we developed. We found, among others, that some aerobic and anaerobic glycolytic enzymes and Krebs cycle enzymes were downregulated, suggesting that apnea may be a result of paucity of oxygen and production of ATP and reducing equivalents. Here, we used twodimensional polyacrylamide gel electrophoresis (2D PAGE) coupled with nanoLC-MS/MS as a complementary approach to investigate the proteins that are dysregulated in the atria from severe and moderate apnea when compared to control. We not only found that the entire glycolytic pathway and Krebs cycle are downregulated, but also found evidence that additional enzymes involved in the betaoxidation, electron transport chain and Krebs cycle anaplerotic reactions were also downregulated. Other protein dysregulations identified are involved in metabolic, structural, or inflammatory pathways, suggesting that these proteins may play a role in atrial pathology developing via chronic obstructive apnea and hypoxia.

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Diurnal variation of circulating microvesicles is associated with the severity of obstructive sleep apnoea

Cited by 20 publications

References 31 publications

Complement system activation in obstructive sleep apnea

Complement system activation in obstructive sleep apnea

Circulating P-Selectin Glycoprotein Ligand 1 and P-Selectin Levels in Obstructive Sleep Apnea Patients

Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using twodimensional polyacrylamide gel electrophoresis and mass spectrometry

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