Abstract
Chronic intermittent hypoxia (CIH) occurring during sleep apnea amplifies infarct
size owing to ischemia-reperfusion. CIH activates hypoxia-inducible factor 1 (HIF-1)
and activating transcription factor 4 (ATF4). However, whether HIF-1 and ATF4 interact
to promote cardiomyocyte death remains unexplored. For the first time, we observed
that in myocardium from apneic patients, CCAAT enhancer–binding protein homologous
protein (CHOP) expression is increased and HIF-1α expression is correlated with sleep
apnea severity. In mice, single-allele deletion of HIF-1α prevents CIH increase in
CHOP expression and infarct size. We uncovered a physical interaction between HIF-1α
and ATF4 in CIH that may represent a novel cardiomyocyte death complex.
Résumé
L'hypoxie intermittente chronique (HIC), qui se est une conséquence du syndrome d'apnées
du sommeil augmente la taille de l'infarctus. La HIC est connue pour activer l'hypoxia
inducible factor-1 (HIF-1) et l’activating transcription factor 4 (ATF4). Cependant, l'existence d'un lien entre HIF-1 et ATF4 dans l'induction pouvant
conduire à la mort des cardiomyocytes reste inexplorée. Pour la première fois, nous
avons observé que dans le myocarde de patients apnéiques, l'expression de CCAAT enhancer-binding protein homologous protein (CHOP) est augmentée et que l'expression de HIF-1 est corrélée avec la sévérité du
syndrome d'apnées du sommeil. Chez la souris, la délétion d'un allèle de HIF-1α empêche
l'augmentation de l'expression de CHOP et de la taille de l'infarctus. Dans le cadre
d’une HIC, nous avons découvert une interaction physique entre HIF-1α et ATF4 qui
pourrait représenter un nouveau complexe impliqué dans la mort cellulaire des cardiomyocytes.
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Article info
Publication history
Published online: April 13, 2020
Accepted:
April 1,
2020
Received:
December 17,
2019
Footnotes
See editorial by Linz et al., pages 809-812 of this issue.
See page 940 for disclosure information.
Identification
Copyright
© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Sleep Apnea, Intermittent Hypoxemia, and Effects on Ischemic Myocardial Damage: Friend or Foe?Canadian Journal of CardiologyVol. 36Issue 6
- PreviewSleep apnea is strongly associated with coronary artery disease, hypertension, heart failure, atrial fibrillation, and sudden death.1-4 In the setting of acute myocardial infarction, the presence of sleep apnea is associated with less myocardial salvage and a smaller reduction in infarct size during recovery.5 Several animal models mimicking chronic intermittent hypoxia as one of the key features of sleep apnea have demonstrated an increased infarct size on ischemia-reperfusion injury,6,7 making chronic intermittent hypoxia a prominent modifier of ischemic myocardial damage.
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