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. METHODS AND 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.
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. METHODS AND 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 obesepatients.
Authors: Mary C Corretti; Todd J Anderson; Emelia J Benjamin; David Celermajer; Francois Charbonneau; Mark A Creager; John Deanfield; Helmut Drexler; Marie Gerhard-Herman; David Herrington; Patrick Vallance; Joseph Vita; Robert Vogel Journal: J Am Coll Cardiol Date: 2002-01-16 Impact factor: 24.094
Authors: T Hori; Y Sugita; E Koga; S Shirakawa; K Inoue; S Uchida; H Kuwahara; M Kousaka; T Kobayashi; Y Tsuji; M Terashima; K Fukuda; N Fukuda Journal: Psychiatry Clin Neurosci Date: 2001-06 Impact factor: 5.188
Authors: Paolo C Colombo; Anthony W Ashton; Sulejman Celaj; Ashok Talreja; Javier E Banchs; Nicholas B Dubois; Massimo Marinaccio; Shailesh Malla; Justine Lachmann; J Anthony Ware; Thierry H Le Jemtel Journal: J Appl Physiol (1985) Date: 2002-03
Authors: Christian Weyer; John S Yudkin; Coen D A Stehouwer; Casper G Schalkwijk; Richard E Pratley; P Antonio Tataranni Journal: Atherosclerosis Date: 2002-03 Impact factor: 5.162
Authors: Nisha I Parikh; Michelle J Keyes; Martin G Larson; Karla M Pou; Naomi M Hamburg; Joseph A Vita; Christopher J O'Donnell; Ramachandran S Vasan; Gary F Mitchell; Udo Hoffmann; Caroline S Fox; Emelia J Benjamin Journal: Obesity (Silver Spring) Date: 2009-03-12 Impact factor: 5.002
Authors: Abd A Tahrani; Asad Ali; Neil T Raymond; Safia Begum; Kiran Dubb; Shanaz Mughal; Biju Jose; Milan K Piya; Anthony H Barnett; Martin J Stevens Journal: Am J Respir Crit Care Med Date: 2012-06-21 Impact factor: 21.405
Authors: Abdelnaby Khalyfa; Chunling Zhang; Ahamed A Khalyfa; Glen E Foster; Andrew E Beaudin; Jorge Andrade; Patrick J Hanly; Marc J Poulin; David Gozal Journal: Sleep Date: 2016-12-01 Impact factor: 5.849