Activation of nuclear factor κB in obstructive sleep apnea: a pathway leading to systemic inflammation
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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.
KeywordsObstructive sleep apnea Nuclear factor κB Cardiovascular disease Inflammation
Funding for this paper was provided by departmental funds.
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