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Endothelial Cell Apoptosis in Obstructive Sleep Apnea

A Link to Endothelial Dysfunction

¹ Western New York Respiratory Research Center, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine; and ² Department of Pathology, University at Buffalo School of Medicine and Biomedical Sciences and the Veterans Affairs Medical Center, Buffalo, New York

Correspondence and requests for reprints should be addressed to Ali A. El Solh, M.D., M.P.H., Division of Pulmonary, Critical Care, and Sleep Medicine, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215. E-mail: solh{at}buffalo.edu

Rationale: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases. Injury of endothelial cells has been advanced as an initial trigger to atherosclerosis.

Objectives: To study the association between circulating apoptotic endothelial cells and vasomotor dysfunction as a function of sleep apnea.

Methods: Brachial artery flow-mediated dilation was determined in 14 subjects with documented OSA and 10 healthy control subjects at baseline and 8 weeks after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146⁺ Annexin V⁺) was performed by flow cytometry.

Measurements and Main Results: Compared with healthy subjects, patients with OSA had higher numbers of circulating CD146⁺ Annexin V⁺ cells (39.2 ± 13.6 cells/mL and17.8 ± 9.4, respectively; p < 0.001). Increased apoptotic endothelial cells correlated moderately with abnormal vascular function (r = –0.61; p = 0.001). A significant correlation was observed between CD146 Annexin V⁺ cells and the apnea-hypopnea index (r = 0.56; p = 0.004). After 8 weeks of treatment with CPAP, the numbers of circulating apoptotic endothelial cells were reduced significantly from 39.2 ± 13.6 to 22.3 ± 12.9 apoptotic cells per milliliter (p < 0.001) and correlated with improvement in endothelium-dependent vasodilation (r = 0.49; p = 0.07).

Conclusions: In patients with OSA, impairment of endothelial-dependent vasodilation correlated with the degree of endothelial cell apoptosis. CPAP therapy led to significant decline in circulating apoptotic endothelial cells. These findings provide an additional mechanism for the predisposition of patients with OSA to premature vascular disease.

Key Words: sleep apnea • endothelium • apoptosis • vasodilation

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Obstructive sleep apnea has been linked to cardiovascular and cerebrovascular morbidity and mortality. Endothelial dysfunction, a precursor of cardiovascular disease, has been associated with sleep apnea. What This Study Adds to the Field Patients with obstructive sleep apnea have higher numbers of circulating apoptic endothelial cells, which correlate with abnormal vascular function. Treatment with CPAP reduces the number of circulating apoptic endothelial cells, which correlated with improvement in endothelium-derived vasodilation.

 

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