Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation.
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.
Division of Pulmonary, Critical Care and Sleep Medicine, Long Island Jewish Medical Center and North Shore University Hospital, New Hyde Park, New York, NY, USA.
Aung K
AK
Htoo
Harly
H
Greenberg
Shraddha
S
Tongia
Guoqian
G
Chen
Todd
T
Henderson
David
D
Wilson
Shu Fang
SF
Liu
D000328:Adult; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood; D045422:Continuous Positive Airway Pressure / Q000379:methods; D018450:Disease Progression; D019040:E-Selectin / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D016328:NF-kappa B / Q000097:blood* / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D017286:Polysomnography; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D019040:E-Selectin; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1