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.
Htoo
Aung K
AK
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.
Greenberg
Harly
H
Tongia
Shraddha
S
Chen
Guoqian
G
Henderson
Todd
T
Wilson
David
D
Liu
Shu Fang
SF
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