Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation

Sleep Breath. 2006 Mar;10(1):43-50. doi: 10.1007/s11325-005-0046-6.

Abstract

Apnea-induced hypoxia and reoxygenation, which generates reactive oxygen species, may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor kappaB (NF-kappaB), increasing systemic inflammation in obstructive sleep apnea. We measured NF-kappaB activity in circulating neutrophils and plasma levels of NF-kappaB-controlled gene products, soluble E (sE)-selectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) in control subjects and in obstructive sleep apnea (OSA) patients. To confirm a causal link with OSA, we reassessed these parameters after nasal continuous positive airway pressure (CPAP) therapy. Twenty-two subjects undergoing evaluation for symptoms of sleep-disordered breathing were grouped by apnea hypopnea index: control, less than 5/h; mild to moderate OSA, 11-40/h; severe OSA, more than 40/h. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kappaB activity was determined by electrophoretic mobility shift assay. Plasma sE-selectin and sVCAM-1 were assayed by enzyme-linked immunosorbent assay. Neutrophils in mild to moderate and severe OSA patients showed 4.8- and 7.9-fold greater NF-kappaB binding activity compared with control subjects (p<0.0001). The degree of NF-kappaB activation was positively correlated with indices of apnea severity. In five severe OSA patients, 1 month of CPAP therapy decreased neutrophil NF-kappaB activation to control levels. sE-selectin and sVCAM concentrations were reduced by CPAP in four of these five subjects. OSA leads to NF-kappaB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease.

MeSH terms

  • Adult
  • Body Mass Index
  • Cardiovascular Diseases / blood
  • Continuous Positive Airway Pressure / methods
  • Disease Progression
  • E-Selectin / blood
  • Female
  • Humans
  • Inflammation / blood*
  • Male
  • NF-kappa B / blood*
  • NF-kappa B / physiology
  • Neutrophils / metabolism
  • Polysomnography
  • Severity of Illness Index
  • Sleep Apnea, Obstructive / blood*
  • Sleep Apnea, Obstructive / physiopathology*
  • Sleep Apnea, Obstructive / therapy
  • Vascular Cell Adhesion Molecule-1 / blood

Substances

  • E-Selectin
  • NF-kappa B
  • Vascular Cell Adhesion Molecule-1