Seminars in Immunopathology

, Volume 31, Issue 1, pp 113–125 | Cite as

Obstructive sleep apnea, immuno-inflammation, and atherosclerosis

  • Claire Arnaud
  • Maurice Dematteis
  • Jean-Louis Pepin
  • Jean-Philippe Baguet
  • Patrick Lévy
Review

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia–reoxygenation. This IH induces several consequences such as hemodynamic, hormonometabolic, oxidative, and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors and is related to the severity of nocturnal hypoxia. Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. Impaired vasoreactivity with endothelial dysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin, and renin–angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. Oxidative stress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease.

Keywords

Atherosclerosis Obstructive sleep apnea Intermittent hypoxia Inflammation Chemokines Adipose tissue 

Abbreviations

AHI

Apnea–hypopnea index

BP

Blood pressure

CPAP

Continuous positive airway pressure

CRP

C-reactive protein

EDS

Excessive daytime sleepiness

ET-1

Endothelin-1

HIF-1

Hypoxia inducible factor-1

ICAM-1

Intercellular adhesion molecule-1

IH

Intermittent hypoxia

IL

Interleukin

IMT

Intima–media thickness

LTB4

Leukotriene B4

MCP-1/CCL2

Monocyte chemoattractant protein-1/C–C chemokine ligand 2

OSA

Obstructive sleep apnea

NFkB

Nuclear factor kappa B

PECAM-1

Platelet endothelial cell adhesion molecule-1

RANTES/CCL5

Regulated upon activation, normal T cell expressed and secreted/C–C chemokine ligand 5

TNF-α

Tumor necrosis factor-alpha

VCAM-1

Vascular cell adhesion molecule-1

Notes

Acknowledgments

This work was supported by a grant from AGIR@dom to CA and MD. CA is recipient of fellowship from the Fondation pour la Recherche Médicale (France).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Claire Arnaud
    • 1
    • 2
  • Maurice Dematteis
    • 1
    • 2
    • 3
  • Jean-Louis Pepin
    • 1
    • 2
    • 3
  • Jean-Philippe Baguet
    • 2
    • 4
    • 5
  • Patrick Lévy
    • 1
    • 2
    • 3
    • 6
  1. 1.INSERM ERI17GrenobleFrance
  2. 2.Faculté de MédecineUniversité Joseph FourierGrenobleFrance
  3. 3.Laboratoires du Sommeil et EFCR, Pole Rééducation et PhysiologieCHUGrenobleFrance
  4. 4.Département de Cardiologie et Hypertension, Hôpital A. MichallonCHUGrenobleFrance
  5. 5.INSERM U877GrenobleFrance
  6. 6.Laboratoire HP2, EFCRCHU GrenobleGrenoble CedexFrance

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