Chronic intermittent hypoxia activates nuclear factor-kappaB in cardiovascular tissues in vivo.
Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-kappaB pathway. We demonstrated that exposure of mice to CIH activated NF-kappaB in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-kappaB activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-kappaB activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-kappaB-dependent gene product. Thus, CIH-mediated NF-kappaB activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients.
Division of Pulmonary, Critical Care and Sleep Medicine, Long Island Jewish Medical Center, The Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, NY, USA.
Harly
H
Greenberg
Xiaobing
X
Ye
David
D
Wilson
Aung K
AK
Htoo
Todd
T
Hendersen
Shu Fang
SF
Liu
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020181:Sleep Apnea, Obstructive / Q000378:metabolism*; D014018:Tissue Distribution
D016328:NF-kappa B