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Rôle de l'hypoxie intermittente dans la maladie ischémique cardiaque associée au Syndrome d'Apnées Obstructives du Sommeil

Abstract : Obstructive sleep apnea syndrome (OSA) is a common disease that affects 6-13% of the middle-aged population. Epidemiological and clinical data support the notion that OSA has a role in the initiation or progression of several cardiovascular (CV) diseases, including myocardial infarction (MI). Indeed, patients hospitalized with acute MI present high prevalence for OSA. Furthermore, OSA is known to major infarct size in patients that persists over time and aggravates long-term adverse events post-MI, as reinfarction, heart failure (HF) and death. OSA is characterized by intermittent hypoxia (IH) which results in desaturation-reoxygenation sequences and appears to be the major consequence of OSA in term of cardiovascular alterations associated with apneas. However, the mechanisms remain unclear. Therefore, the understanding of pathophysiologic mechanisms involved in cardiac disorders is a research priority for OSA in order to develop new therapeutic targets and improve the management of CV risk in apneic patients. There are growing evidences suggesting a major role of endoplasmic reticulum (ER) stress and HIF-1 activation in the vulnerability to acute ischemic events and in long-term adverse complications associated with prolonged MI. Furthermore, the progression of ischemic cardiomyopathy following MI is also associated with activation of the sympathetic nervous system which substantially contributes to cardiac alterations. Furthermore, these are three mechanisms known to be activated with IH. This project aimed 1) to assess the IH-induced acute and chronic cardiac alterations following MI, 2) to study the implication of cellular mechanisms involved in the adverse ischemic events related to OSA.We have shown that IH increases infarct size following acute MI and aggravates cardiac remodeling and contractile dysfunction in a rat model of chronic ischemic cardiomyopathy. In these contexts, IH is associated with a sympathetic over activity, a proapoptotic ER stress and the activation of HIF-1, which substantially contribute to increased heart vulnerability to infarction and worsening of long-term heart complications post-MI. These different factors may represent interesting biomarkers for predicting CV risk in severe apneic patients and may be considered as potential therapeutic targets to improve the management of OSA patients with high CV risks.
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Submitted on : Tuesday, December 18, 2018 - 10:34:06 AM
Last modification on : Tuesday, May 19, 2020 - 9:32:29 AM
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  • HAL Id : tel-01958618, version 1



Guillaume Bourdier. Rôle de l'hypoxie intermittente dans la maladie ischémique cardiaque associée au Syndrome d'Apnées Obstructives du Sommeil. Cardiologie et système cardiovasculaire. Université Grenoble Alpes, 2017. Français. ⟨NNT : 2017GREAS049⟩. ⟨tel-01958618⟩



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