Abstract

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and associated with the disruption of circadian rhythm. The study aimed to assess the relationship between hypoxia-inducible factor (HIF) subunits, circadian clock proteins, and polysomnography (PSG) variables, in healthy individuals and severe OSA patients. The study included 20 individuals, who underwent PSG and were divided into severe OSA group (n = 10; AHI ≥ 30) and healthy control (n = 10; AHI < 5) based on apnea-hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. HIF-1α, HIF-1β, BMAL1, CLOCK, CRY1, and PER1 protein concertation measurements were performed using ELISA. In a multivariate general linear model with the concentration of all circadian clock proteins as dependent variables, evening HIF-1α protein level was the only significant covariant (p = 0.025). Corrected models were significant for morning and evening PER1 (p = 0.008 and p = 0.006, respectively), evening (p = 0.043), and evening BMAL protein level (p = 0.046). In corrected models, evening HIF-1α protein level had an influence only on the evening PER1 protein level. Results suggest that OSA patients are at risk for developing circadian clock disruption. This process might be mediated by subunit α of HIF-1, as its increased protein level is associated with overexpression of circadian clock proteins.

Highlights

  • Obstructive sleep apnea syndrome (OSA) is a chronic condition characterized by recurrent pauses in breathing during sleep, which leads to intermittent hypoxia (IH), hypercapnia, arousals, and sleep fragmentation

  • We demonstrate that levels of circadian clock proteins in peripheral blood are increased in OSA compared to healthy individuals, which might suggest that they are likely to suffer

  • We demonstrate that levels of circadian clock proteins in peripheral blood are increased in OSA compared to healthy individuals, which might suggest that they are likely to suffer from dysregulation of the circadian rhythm

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Summary

Introduction

Obstructive sleep apnea syndrome (OSA) is a chronic condition characterized by recurrent pauses in breathing during sleep, which leads to intermittent hypoxia (IH), hypercapnia, arousals, and sleep fragmentation. Recent studies suggest that the prevalence of sleep disordered breathing drastically increased and in moderate or severe form might affect up to 50% men and 24% women [1]. One of the typical complications of sleep disordered breathing is recurrent hypoxia, which subsequently causes modifications of gene expression. The main factor responsible for oxygen metabolism homeostasis is hypoxia-inducible factor 1 (HIF-1). It is a heterodimeric complex, which consists of two subunits: α (HIF-1α) and β (HIF-1β). Recent studies have shown that HIF-1α serum protein level is chronically increased in OSA patients and is not reverted by one-night continuous positive air pressure therapy [3,4]

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