Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1α protein

Abstract

Study Objectives: Obstructive sleep apnea (OSA) is a chronic condition that is characterized by recurrent pauses in breathing during sleep causing intermittent hypoxia. The main factor responsible for oxygen metabolism homeostasis is hypoxia-inducible factor 1 (HIF-1), comprised of 2 subunits: α (oxygen sensitive) and β. The aim of the study was to investigate the HIF-1α serum protein level and mRNA HIF-1α expression in patients with OSA and a healthy control group and determine their evening-morning variation and association with polysomnography parameters. Methods: Eighty-four individuals were enrolled in the study. All patients underwent polysomnography examination and based on the results were divided into 2 groups: OSA group (n = 60) and control group (n = 24). Peripheral blood was collected in the evening before and in the morning after the polysomnography. HIF-1α expression was evaluated on protein in blood serum and mRNA level in peripheral blood leukocytes. Results: HIF-1α serum protein concentration was higher in patients with OSA compared with control patients in both the evening (1,490.1 vs. 727.0 pg/mL; P <.001) and the morning (1,368.9 vs. 702.1 pg/mL; P <.001) samples. There was no difference between evening and morning HIF-1α serum protein level in either group. No differences were observed in HIF-1α mRNA expression between the OSA and control group. Additionally, evening and morning HIF-1α serum protein level correlated with number of desaturations during sleep (r = .384, P < .001 and r = .433, P < .001, respectively). Conclusions: Observed differences in HIF-1α serum protein level between the OSA and the control groups without difference between evening and morning measurements suggest chronic increase in this protein concentration by intermittent nocturnal hypoxia in OSA.

Triglyceride-Glucose Index in Non-Diabetic, Non-Obese Patients with Obstructive Sleep Apnoea

“…In line with the literature [ 8 ], chronic intermittent hypoxaemia was the predominant mechanism leading to augmented insulin resistance in patients with OSA in our study. Chronic intermittent hypoxaemia induces the expression of hypoxia-inducible factor 1 (HIF-1) [ 30 , 31 ] which is a key factor in the regulation of metabolism [ 32 ]. However, sleep fragmentation, sleep restriction or sleep deprivation could also contribute to insulin resistance [ 33 ].…”

HIF-1α as a Mediator of Insulin Resistance, T2DM, and Its Complications: Potential Links With Obstructive Sleep Apnea

“…Increased level of HIF-1α level in serum was observed in OSA patients compared to controls, regardless of measurement method (ELISA/western blot) ( Lu et al, 2016 ; Gabryelska et al, 2019 ). Lack of difference between evening and morning concentrations suggests its chronic increasement caused by intermittent nocturnal hypoxia among OSA patients ( Gabryelska et al, 2020c ). Furthermore, one-night of CPAP therapy seems to be not sufficient to affect the increased level of the protein ( Gabryelska et al, 2020b ).…”

The Role of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 in Obstructive Sleep Apnoea

“…In addition, LRP-1 expression is induced by vitamin D [26] as well as by the klotho protein [27] which are both decreased in OSA [18,28]. Hypoxia inducible factor-1 alpha (HIF-1α) activated by IH is highly expressed in OSA [29][30][31][32]. Recently HIF-1α have been suggested to mediate OSA-associated metabolic abnormalities [33] and contribute to increased LRP-1 levels [34,35].…”