Journal Article

Elucidating the Interplay of Hypoxia-Inducible Factor and Circadian Clock Signaling in Obstructive Sleep Apnea Patients

Strzelecki, Dominik, Ditmer, Marta, Gajewski, Adrian, Sochal, Marcin, Turkiewicz, Szymon, Białasiewicz, Piotr, Gabryelska, Agata, Chałubiński, Maciej

2025

Overview

Background: Hypoxia-inducible factor 1 (HIF-1) affects the circadian clock in obstructive sleep apnea (OSA) and may have a bidirectional relationship with circadian mechanisms. This study examined the link between circadian clock and HIF-1 in OSA patients versus controls. Methods: 70 participants underwent polysomnography (PSG), and were assigned into OSA (apnea–hypopnea index (AHI) ≥ 5, n = 54) or control (AHI < 5, n = 16) groups. BMAL1 (brain and muscle ARNT like 1), CLOCK (circadian locomotor output cycles kaput), PER1 (period 1), CRY1 (cryptochrome 1), HIF-1α, and HIF-1β gene expressions and protein levels were measured in evening and morning samples, collected before and after PSG. Results: The OSA group was characterized by increased CLOCK, CRY1, PER1 and HIF-1a protein levels, both in the morning and evening (all p < 0.05), and decreased morning expression of BMAL1 (p = 0.02). Associations between almost all circadian clock gene expressions and both HIF-1 subunits were observed in the OSA group at both time points (all p < 0.05), apart from association between PER1 and HIF-1α in the morning (R = 0.050, p = 0.73). In controls, only a correlation between HIF-1α levels and CRY1 expression in the morning (R = 0.588, p = 0.02) was found. Conclusions: OSA affects the circadian clock and HIF-1 pathway, with increased CLOCK, CRY1, PER1, and HIF-1α protein levels observed in OSA patients. The interplay between these systems may involve complex posttranscriptional and posttranslational mechanisms.

• Publisher: MDPI AG,MDPI
• Subject: Adult / ARNTL Transcription Factors - genetics / ARNTL Transcription Factors - metabolism / Circadian Clocks - genetics / Circadian rhythm / Circadian rhythms / CLOCK Proteins - genetics / CLOCK Proteins - metabolism / Cryptochromes - genetics / Cryptochromes - metabolism / Development and progression / Enzymes / Female / Gene expression / Gene Expression Regulation / Genetic aspects / Health aspects / Humans / Hypoxia / Hypoxia-Inducible Factor 1 - genetics / Hypoxia-Inducible Factor 1 - metabolism / Hypoxia-Inducible Factor 1, alpha Subunit - genetics / Hypoxia-Inducible Factor 1, alpha Subunit - metabolism / Male / Middle Aged / Physiological aspects / Polysomnography / Proteins / Signal Transduction / Sleep apnea / Sleep apnea syndromes / Sleep Apnea, Obstructive - genetics / Sleep Apnea, Obstructive - metabolism / Transcription factors