Published ahead of print on February 1, 2007, doi:10.1164/rccm.200611-1598OC
Am. J. Respir. Crit. Care Med., Volume 175, Number 11, June 2007, 1186-1191
A more recent version of this article appeared on June 1, 2007
Submitted on November 6, 2006
Accepted on February 1, 2007
Endothelial Cell Apoptosis in Obstructive Sleep Apnea: A Link to Endothelial Dysfunction
Ali A El Solh1*, Morohunfolu E Akinnusi1, Fadi H Baddoura2, and Corey R Mankowski1
1 Western New York Respiratory Research Center, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University at Buffalo School of Medicine and Biomedical Sciences and the Veterans Affairs Medical Center, Buffalo, NY, USA,
2 Department of Pathology, University at Buffalo School of Medicine and Biomedical Sciences and the Veterans Affairs Medical Center, Buffalo, NY, USA
* To whom correspondence should be addressed. 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. Objective: 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 post continuous positive airway pressure therapy (CPAP) . 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 and 17.8±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 also observed between CD146 Annexin V+ cells and the apnea hypopnea index (r= 0.56; p=0.004). Following 8 weeks 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 ml (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 OSA patients to premature vascular disease.
Key words: sleep apnea, endothelium, apoptosis, vasodilation
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