Seminars in Immunopathology

, Volume 31, Issue 1, pp 113–125

Obstructive sleep apnea, immuno-inflammation, and atherosclerosis

Authors

  • Claire Arnaud
    • INSERM ERI17
    • Faculté de MédecineUniversité Joseph Fourier
  • Maurice Dematteis
    • INSERM ERI17
    • Faculté de MédecineUniversité Joseph Fourier
    • Laboratoires du Sommeil et EFCR, Pole Rééducation et PhysiologieCHU
  • Jean-Louis Pepin
    • INSERM ERI17
    • Faculté de MédecineUniversité Joseph Fourier
    • Laboratoires du Sommeil et EFCR, Pole Rééducation et PhysiologieCHU
  • Jean-Philippe Baguet
    • Faculté de MédecineUniversité Joseph Fourier
    • Département de Cardiologie et Hypertension, Hôpital A. MichallonCHU
    • INSERM U877
    • INSERM ERI17
    • Faculté de MédecineUniversité Joseph Fourier
    • Laboratoires du Sommeil et EFCR, Pole Rééducation et PhysiologieCHU
    • Laboratoire HP2, EFCRCHU Grenoble
Review

DOI: 10.1007/s00281-009-0148-5

Cite this article as:
Arnaud, C., Dematteis, M., Pepin, J. et al. Semin Immunopathol (2009) 31: 113. doi:10.1007/s00281-009-0148-5

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

AtherosclerosisObstructive sleep apneaIntermittent hypoxiaInflammationChemokinesAdipose 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

Copyright information

© Springer-Verlag 2009