J Clin Neurol.  2010 Jun;6(2):89-98. 10.3988/jcn.2010.6.2.89.

Increased Circulating Endothelial Microparticles and Carotid Atherosclerosis in Obstructive Sleep Apnea

Affiliations
  • 1Department of Neurology, Inha University College of Medicine, Incheon, Korea.
  • 2Department of Neurology, Seoul National University College of Medicine, Seoul, Korea. rohjk777@gmail.com
  • 3Department of Occupational and Environmental Medicine, Inha University College of Medicine, Incheon, Korea.

Abstract

BACKGROUND AND PURPOSE
Endothelial impairment is a linking mechanism between obstructive sleep apnea (OSA) and cardiovascular diseases. Profiles of endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. The aims of this study were to measure the levels of EMPs and progenitor cells in OSA, determine the correlations between these factors and OSA severity and the degree of atherosclerosis, and document any changes in these factors after therapy.
METHODS
Subjects with (n=82) and without (n=22) OSA were recruited prospectively. We measured the number of colony-forming units (CFU) in cell culture as the endothelial progenitor cell index, and the number of EMPs using flow cytometry with CD31 [platelet endothelial cell adhesion molecule (PECAM)], CD42 (platelet glycoprotein), annexin V, and CD62E (E-selectin) antibodies at baseline and after 4-6 weeks of continuous positive airway pressure (CPAP) therapy. Carotid intima-media thickness (IMT) was regarded as a marker of atherosclerosis.
RESULTS
The levels of PECAM+CD42- (p<0.001), PECAM+annexin V+ (p<0.001), and E-selectin+ microparticles (p=0.001) were higher in OSA subjects than in non-OSA subjects. The number of CFU did not differ between the two groups. OSA severity independently predicted the levels of PECAM+CD42- (p=0.02) and PECAM+annexin V+ (p=0.004). Carotid IMT was correlated with OSA severity (p<0.001), PECAM+CD42- (p=0.03), and PECAM+annexin V+ (p=0.01). Neither OSA severity nor carotid IMT was correlated with either the number of CFU or E-selectin+. CPAP therapy decreased the occurrence of E-selectin+ (p<0.001) in 21 of the OSA subjects, but had no effect on the other microparticles of the number of CFU.
CONCLUSIONS
OSA led to the overproduction of EMPs, which moderately correlated with OSA severity and the degree of atherosclerosis, and partly responded to therapy. The endothelial impairment might contribute to future cardiovascular events.

Keyword

atherosclerosis; endothelium; progenitor cells; continuous positive airway pressure; colony-forming units assay

MeSH Terms

Annexin A5
Antibodies
Atherosclerosis
Cardiovascular Diseases
Carotid Artery Diseases
Carotid Intima-Media Thickness
Cell Culture Techniques
Colony-Forming Units Assay
Continuous Positive Airway Pressure
Endothelial Cells
Endothelium
Flow Cytometry
Prospective Studies
Sleep Apnea, Obstructive
Stem Cells
Annexin A5
Antibodies

Figure

  • Fig. 1 Correlation between apnea hypopnea index (AHI) and levels of endothelial microparticles (EMPs). AHI was correlated with platelet endothelial cell adhesion molecule (PECAM)+CD42- EMPs (r=0.28, p=0.01) and PECAM+ annexin V+ EMPs (r=0.36, p=0.001).

  • Fig. 2 Correlations of carotid intima-media thickness (IMT) with obstructive sleep apnea severity and EMP levels. Apnea-hypopnea index (AHI) (r=0.71, p<0.001) and levels of PECAM+CD42- (r=0.27, p=0.01) and PECAM+annexin V+ EMPs (r=0.33, p=0.001) were correlated with IMT.

  • Fig. 3 Blood E-selectin+ EMPs in 21 patients with obstructive sleep apnea before and after continuous positive airway pressure therapy. Changes in the log-transformed value of E-selectin+ EMPs are shown (p<0.001).


Cited by  1 articles

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Bomi Kim, Eun Mi Lee, Yoo-Sam Chung, Woo-Sung Kim, Sang-Ahm Lee
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