Increased Circulating Endothelial Microparticles and Carotid Atherosclerosis in Obstructive Sleep Apnea

Abstract

Background and PurposeEndothelial 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.MethodsSubjects 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.ResultsThe 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.ConclusionsOSA 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.

Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

“…In patients with obstructive sleep apnea, circulating endothelial MP concentrations negatively correlate with flow-mediated vasodilation and carotid-intima thickness (26 ). An increase in plasma endothelial MPs has also been observed in patients who were briefly exposed to second-hand smoke (27 ).…”

Systematic and Endothelial Inflammation and Endothelial Progenitor Cell Levels in Emphysematous Rats Exposed to Intermittent Hypoxia

“…33 Several previous studies have investigated the association between OSA and EPC. Findings have been controversial, with negative, 35 neutral, 36 and positive results. 33 A possible reason for this discrepancy may be that these studies were performed on only a small number of participants and/or different markers were used to characterize these cells.…”

“…It should also be pointed out that investigators in different studies assessed circulating EPCs through different methods. Whereas some studies assessed circulating EPCs using flow cytometry alone, 35,40 another study assessed circulating EPCs by the assay of endothelial colony-forming units. 35 In addition, the EPCs studied by one group are not necessarily the same cell type as those of another.…”

“…Whereas some studies assessed circulating EPCs using flow cytometry alone, 35,40 another study assessed circulating EPCs by the assay of endothelial colony-forming units. 35 In addition, the EPCs studied by one group are not necessarily the same cell type as those of another. One of the major limitations in studying EPCs is the lack of unifying phenotypic markers that are employed by different investigators.…”

Microparticles and vascular dysfunction in obstructive sleep apnoea

“…Some studies proposed additional venepunctures at 04:00 h [49] and 17:00 h [56] to access the night to morning or the evening to morning changes. Two studies used EDTA tubes [52,55] and four studies used citrate tubes [49,50,51,53]. The speed of centrifugation ranged from 10006g [50] (MPs remain in the supernatant) to 20 0006g [54] (MPs are pelleted) and the duration of the centrifugation ranged from 6 to 90 min.…”