title: Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.
abstract: Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and atherosclerosis evolves from activation of the inflammatory cascade. We propose that activation of the nuclear factor kappaB (NF-kappaB), a key transcription factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking, and non-hypertensive men with OSA symptoms and seven similar healthy subjects were recruited for standard polysomnography followed by the collection of blood samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF-alpha) were measured at the same time and after the next night of continuous positive airway pressure (CPAP). p65 Concentrations in the OSA group were significantly higher than in the control group [median, 0.037 ng/microl (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range, 0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r = 0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to 0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26 (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to 12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing. Such activation of NF-kappaB may contribute to the pathogenesis of atherosclerosis in OSA patients.
authors.affiliation: Second Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. mountain@pastel.ocn.ne.jp
authors.forename: Motoo
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Tamaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Tomoda
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Fukuoka
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Makinodan
authors.forename: Noriko
authors.initials: N
authors.lastname: Koyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000276:immunology; D002478:Cells, Cultured; D045422:Continuous Positive Airway Pressure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D017286:Polysomnography; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha