Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction.
BACKGROUND
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 after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146(+) Annexin V(+)) was performed by flow cytometry.


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 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.
El Solh
Ali A
AA
Division of Pulmonary, Critical Care, and Sleep Medicine, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215, USA. solh@buffalo.edu
Akinnusi
Morohunfolu E
ME
Baddoura
Fadi H
FH
Mankowski
Corey R
CR
D000328:Adult; D017304:Annexin A5 / Q000276:immunology; D017209:Apoptosis; D001916:Brachial Artery / Q000503:physiopathology; D051929:CD146 Antigen / Q000276:immunology; D045422:Continuous Positive Airway Pressure; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D011379:Prognosis; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D014664:Vasodilation / Q000502:physiology*
D017304:Annexin A5; D051929:CD146 Antigen