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(Circulation. 2008;117:2270-2278.)
© 2008 American Heart Association, Inc.

Vascular Medicine

Inflammation, Oxidative Stress, and Repair Capacity of the Vascular Endothelium in Obstructive Sleep Apnea

Sanja Jelic, MD; Margherita Padeletti, MD; Steven M. Kawut, MD, MS; Christopher Higgins, MD; Stephen M. Canfield, MD; Duygu Onat, PhD; Paolo C. Colombo, MD; Robert C. Basner, MD; Phillip Factor, DO; Thierry H. LeJemtel, MD

From the Division of Pulmonary, Allergy, and Critical Care Medicine (S.J., M.P., S.M.K., C.H., S.M.C., R.C.B., P.F.), Department of Epidemiology (S.M.K.), and Division of Cardiology (D.O., P.C.C.), Columbia University College of Physicians and Surgeons, New York, NY; and Division of Cardiology (T.H.L.), Tulane University School of Medicine, New Orleans, La.

Correspondence to Sanja Jelic, MD, Columbia University College of Physicians and Surgeons, Division of Pulmonary, Allergy, and Critical Care Medicine, PH8 Center, Room 840, 630 W 168th St, New York, NY 10032. E-mail sj366{at}columbia.edu

Received September 20, 2007; accepted February 29, 2008.

Background— Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed.

Methods and Results— Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP 4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP 4 hours daily.

Conclusions— OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.

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