Vascular inflammation in obesity and sleep apnea.
BACKGROUND
Unrecognized obstructive sleep apnea (OSA) is highly prevalent in obesity. Both obesity and OSA are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. We investigated directly whether the endothelial alterations that are attributed commonly to obesity are in fact related to OSA.


RESULTS
Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, we quantified the expression of nuclear factor-kappaB and nitrotyrosine by immunofluorescence in freshly harvested venous endothelial cells. To evaluate basal endothelial nitric oxide (NO) production and activity, we quantified the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation. Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (n=38) than in OSA-free subjects (n=33) regardless of central adiposity. Expression of nuclear factor-kappaB was greater in obese OSA patients than in obese OSA-free subjects (P=0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased whereas expression of nitrotyrosine and nuclear factor-kappaB significantly decreased in OSA patients who adhered to continuous positive airway pressure >/=4 hours daily.


CONCLUSIONS
Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients.
Columbia University College of Physicians and Surgeons, Division of Pulmonary, Allergy, and Critical Care Medicine, PH8 Center, Room 101, 630 W 168th St, New York, NY 10032, USA. sj366@columbia.edu
Sanja
S
Jelic
David J
DJ
Lederer
Tessa
T
Adams
Margherita
M
Padeletti
Paolo C
PC
Colombo
Phillip H
PH
Factor
Thierry H
TH
Le Jemtel
D000328:Adult; D016022:Case-Control Studies; D045422:Continuous Positive Airway Pressure; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology; D017286:Polysomnography; D011446:Prospective Studies; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D014657:Vasculitis / Q000209:etiology / Q000503:physiopathology*
D016328:NF-kappa B; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III