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Am. J. Respir. Crit. Care Med., Volume 165, Number 7, April 2002, 934-939

Increased Adhesion Molecules Expression and Production of Reactive Oxygen Species in Leukocytes of Sleep Apnea Patients

LARISSA DYUGOVSKAYA, PERETZ LAVIE, and LENA LAVIE

Unit of Anatomy and Cell Biology and Sleep Laboratory, Technion-Israel Institute of Technology, The Bruce Rappaport Faculty of Medicine, Haifa, Israel

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Free radicals and adhesion molecules were implicated in the pathogenesis of atherosclerosis leading to cardiovascular disorders. Therefore, we investigated the link between CD15, CD11c, CD11b, and CD64 expression on leukocytes and their ability to generate reactive oxygen species (ROS) in patients with OSA and control volunteers. We also studied the effects of hypoxia in vitro on monocytes from control subjects and the ability of monocytes from both groups to adhere to human endothelial cells in culture. The effect of nasal continuous positive airway pressure (nCPAP) treatment was studied as well. We found that OSA was associated with increased expression of adhesion molecules CD15 and CD11c on monocytes, increased adherence of monocytes in culture to human endothelial cells, increased intracellular ROS production in some monocyte and granulocyte subpopulations, and upregulation of CD15 expression due to hypoxia in vitro in monocytes of control subjects. Furthermore, nCPAP treatment was associated with downregulation of CD15 and CD11c monocyte expression and decreased basal ROS production in CD11c+ monocytes. Monocyte adherence to endothelial cells decreased as well. Our findings provide one of the possible mechanisms for explaining the high rate of cardiovascular morbidity in patients with sleep apnea.




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S. M. Caples, A. S. Gami, and V. K. Somers
Obstructive Sleep Apnea
Ann Intern Med, February 1, 2005; 142(3): 187 - 197.
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 Am. J. Respir. Crit. Care Med.Home page
A. G. Kaditis, E. I. Alexopoulos, E. Kalampouka, E. Kostadima, A. Germenis, E. Zintzaras, and K. Gourgoulianis
Morning Levels of C-Reactive Protein in Children with Obstructive Sleep-disordered Breathing
Am. J. Respir. Crit. Care Med., February 1, 2005; 171(3): 282 - 286.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
R. Schulz, W. Seeger, C. Fegbeutel, H. Husken, R. H. Bodeker, H. Tillmanns, and M. Grebe
Changes in extracranial arteries in obstructive sleep apnoea
Eur. Respir. J., January 1, 2005; 25(1): 69 - 74.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
T. Tazaki, K. Minoguchi, T. Yokoe, K. T. R. Samson, H. Minoguchi, A. Tanaka, Y. Watanabe, and M. Adachi
Increased Levels and Activity of Matrix Metalloproteinase-9 in Obstructive Sleep Apnea Syndrome
Am. J. Respir. Crit. Care Med., December 15, 2004; 170(12): 1354 - 1359.
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 Eur Respir JHome page
A.G. Kaditis, E.I. Alexopoulos, E. Kalampouka, E. Kostadima, N. Angelopoulos, A. Germenis, E. Zintzaras, and K. Gourgoulianis
Morning levels of fibrinogen in children with sleep-disordered breathing
Eur. Respir. J., November 1, 2004; 24(5): 790 - 797.
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 ChestHome page
K. Minoguchi, T. Tazaki, T. Yokoe, H. Minoguchi, Y. Watanabe, M. Yamamoto, and M. Adachi
Elevated Production of Tumor Necrosis Factor-{alpha} by Monocytes in Patients With Obstructive Sleep Apnea Syndrome
Chest, November 1, 2004; 126(5): 1473 - 1479.
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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Svatikova, R. Wolk, H. H. Wang, M. E. Otto, K. A. Bybee, R. J. Singh, and V. K. Somers
Circulating free nitrotyrosine in obstructive sleep apnea
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R284 - R287.
[Abstract] [Full Text] [PDF]

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 Mayo Clin Proc.Home page
J. M. Parish and V. K. Somers
Obstructive Sleep Apnea and Cardiovascular Disease
Mayo Clin. Proc., August 1, 2004; 79(8): 1036 - 1046.
[Abstract] [PDF]

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 ChestHome page
U. Hatipoglu and I. Rubinstein
Inflammation and Obstructive Sleep Apnea Syndrome: How Many Ways Do I Look at Thee?
Chest, July 1, 2004; 126(1): 1 - 2.
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 ChestHome page
C. W. Atwood Jr, D. McCrory, J. G. N. Garcia, S. H. Abman, and G. S. Ahearn
Pulmonary Artery Hypertension and Sleep-Disordered Breathing: ACCP Evidence-Based Clinical Practice Guidelines
Chest, July 1, 2004; 126(1_suppl): 72S - 77S.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
O. Milleron, R. Pilliere, A. Foucher, F. de Roquefeuil, P. Aegerter, G. Jondeau, B. G Raffestin, and O. Dubourg
Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study
Eur. Heart J., May 1, 2004; 25(9): 728 - 734.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
G J Gibson
Sleep disordered breathing and the outcome of stroke
Thorax, May 1, 2004; 59(5): 361 - 363.
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 J. Appl. Physiol.Home page
J. B. Dean, D. K. Mulkey, R. A. Henderson III, S. J. Potter, and R. W. Putnam
Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons
J Appl Physiol, February 1, 2004; 96(2): 784 - 791.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
F. J. Nieto, D. M. Herrington, S. Redline, E. J. Benjamin, and J. A. Robbins
Sleep Apnea and Markers of Vascular Endothelial Function in a Large Community Sample of Older Adults
Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 354 - 360.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. S. M. Ip, H.-F. Tse, B. Lam, K. W. T. Tsang, and W.-K. Lam
Endothelial Function in Obstructive Sleep Apnea and Response to Treatment
Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 348 - 353.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. Lavie
Pro: Sleep Apnea Causes Cardiovascular Disease
Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 147 - 148.
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 Am. J. Respir. Crit. Care Med.Home page
G. Sampol, O. Romero, A. Salas, J. L. Tovar, P. Lloberes, T. Sagales, and A. Evangelista
Obstructive Sleep Apnea and Thoracic Aorta Dissection
Am. J. Respir. Crit. Care Med., December 15, 2003; 168(12): 1528 - 1531.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
R. Wolk, A. S.M. Shamsuzzaman, and V. K. Somers
Obesity, Sleep Apnea, and Hypertension
Hypertension, December 1, 2003; 42(6): 1067 - 1074.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
J. B. Dean, D. K. Mulkey, A. J. Garcia III, R. W. Putnam, and R. A. Henderson III
Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures
J Appl Physiol, September 1, 2003; 95(3): 883 - 909.
[Abstract] [Full Text] [PDF]

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 ChestHome page
M. Hayashi, K. Fujimoto, K. Urushibata, S.-i. Uchikawa, H. Imamura, and K. Kubo
Nocturnal Oxygen Desaturation Correlates With the Severity of Coronary Atherosclerosis in Coronary Artery Disease
Chest, September 1, 2003; 124(3): 936 - 941.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
L. Dyugovskaya, P. Lavie, and L. Lavie
Phenotypic and Functional Characterization of Blood {gamma}{delta} T Cells in Sleep Apnea
Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 242 - 249.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
Y.-J. Peng and N. R. Prabhakar
Reactive oxygen species in the plasticity of respiratory behavior elicited by chronic intermittent hypoxia
J Appl Physiol, June 1, 2003; 94(6): 2342 - 2349.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
T. D. Bradley and J. S. Floras
Sleep Apnea and Heart Failure: Part I: Obstructive Sleep Apnea
Circulation, April 1, 2003; 107(12): 1671 - 1678.
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 JAMAHome page
B. Phillips
Definitions of the Metabolic Syndrome
JAMA, March 12, 2003; 289(10): 1241 - 1241.
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 CirculationHome page
T. Yokoe, K. Minoguchi, H. Matsuo, N. Oda, H. Minoguchi, G. Yoshino, T. Hirano, and M. Adachi
Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients With Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure
Circulation, March 4, 2003; 107(8): 1129 - 1134.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, and Pulmonary Function Testing in AJRCCM 2002
Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 306 - 318.
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