Cooperation Between Hypoxia-Inducible Factor 1α and Activating Transcription Factor 4 in Sleep Apnea-Mediated...

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Sleep Medicine

Background:

• Chronic intermittent hypoxia (CIH) exacerbates myocardial infarct size through ischemia-reperfusion injury.
• CIH is known to activate hypoxia-inducible factor 1 (HIF-1) and activating transcription factor 4 (ATF4).
• The potential interaction between HIF-1 and ATF4 in promoting cardiomyocyte death remains uninvestigated.

Purpose of the Study:

• To investigate the interaction between HIF-1 and ATF4 in the context of CIH-induced cardiomyocyte death.
• To explore the role of this interaction in amplifying infarct size during sleep apnea.

Main Methods:

• Analysis of myocardial tissue from patients with sleep apnea.
• Assessment of CCAAT enhancer-binding protein homologous protein (CHOP) and HIF-1α expression levels.
• Utilizing a mouse model with single-allele deletion of HIF-1α to study CIH effects.
• Investigating the physical interaction between HIF-1α and ATF4 under CIH conditions.

Main Results:

• Increased expression of CHOP and HIF-1α in myocardium from apneic patients.
• HIF-1α expression correlated with sleep apnea severity.
• Single-allele deletion of HIF-1α in mice abrogated CIH-induced increases in CHOP expression and infarct size.
• A physical interaction between HIF-1α and ATF4 was identified in CIH.

Conclusions:

• HIF-1α and ATF4 form a novel complex that contributes to cardiomyocyte death during CIH.
• This interaction represents a potential therapeutic target for mitigating heart damage in sleep apnea.