Activation of nuclear factor κB in obstructive sleep apnea: a pathway leading to systemic inflammation
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- Htoo, A.K., Greenberg, H., Tongia, S. et al. Sleep Breath (2006) 10: 43. doi:10.1007/s11325-005-0046-6
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Apnea-induced hypoxia and reoxygenation, which generates reactive oxygen species, may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor κB (NF-κB), increasing systemic inflammation in obstructive sleep apnea. We measured NF-κB activity in circulating neutrophils and plasma levels of NF-κB-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-κB 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-κB binding activity compared with control subjects (p<0.0001). The degree of NF-κB activation was positively correlated with indices of apnea severity. In five severe OSA patients, 1 month of CPAP therapy decreased neutrophil NF-κB activation to control levels. sE-selectin and sVCAM concentrations were reduced by CPAP in four of these five subjects. OSA leads to NF-κB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease.