Jinkwan Kim1, Rakesh Bhattacharjee1, Leila Kheirandish-Gozal1, Karen Spruyt1, David Gozal2. 1. Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, University of Chicago, Chicago, IL; Division of Pediatric Sleep Medicine, University of Louisville School of Medicine, Louisville, KY. 2. Section of Pediatric Sleep Medicine, Department of Pediatrics, Comer Children's Hospital, University of Chicago, Chicago, IL; Division of Pediatric Sleep Medicine, University of Louisville School of Medicine, Louisville, KY. Electronic address: dgozal@uchicago.edu.
Abstract
BACKGROUND: Endothelial dysfunction is a common complication of pediatric obstructive sleep apnea (OSA). Circulating cell-derived microparticles (MPs) have emerged as reliable biomarkers of endothelial dysfunction and atherosclerosis. METHODS: Children underwent blood drawing the morning after a sleep study. Endothelial function was assessed using a modified hyperemic test after cuff-induced occlusion of the brachial artery. Circulating MP levels in plasma, including levels of endothelial MPs, endothelial progenitor MPs, leukocyte MPs, and platelet MPs, were measured using flow cytometry after staining with cell-specific antibodies. RESULTS: The levels of endothelial MPs, endothelial progenitor MPs, leukocyte MPs, and platelet MPs were significantly different according to the severity of OSA in children. Leukocyte CD11b+ MPs and platelet CD41a+ MPs correlated with the apnea-hypopnea index (AHI) (r = 0.334, P < .001; and r = 0.301, P < .001, respectively), and associations emerged between leukocyte CD11b+ MPs and apolipoprotein B (r = 0.206, P < .05) and between endothelial MPs and low-density lipoprotein cholesterol (r = 0.240, P < .01). In a multivariate regression model, the BMI z score (β ± SE, 0.045 ± 0.020; P = .020) and the CD41a MPs to leukocyte CD45 MPs ratio (β ± SE, 0.074 ± 0.032; P = .021) were independently associated with peak hyperemic responses. After controlling for age, gender, race, BMI z score, and apolipoprotein B levels, endothelial MPs, endothelial progenitor MPs, and leukocyte MPs showed independent associations with the AHI. Complex significant associations emerged between endothelial function, the AHI, and CD41a MPs. CONCLUSIONS: Childhood OSA is associated with higher circulating MP levels that can promote cardiovascular risk. Platelet-derived MPs emerge as being significantly associated with the vascular dysfunction associated with OSA in children and could potentially account for increased risk for altered endothelial function. However, the clinical use of MPs as reliable biomarker indicators of vascular risk will have to await further studies.
BACKGROUND:Endothelial dysfunction is a common complication of pediatric obstructive sleep apnea (OSA). Circulating cell-derived microparticles (MPs) have emerged as reliable biomarkers of endothelial dysfunction and atherosclerosis. METHODS:Children underwent blood drawing the morning after a sleep study. Endothelial function was assessed using a modified hyperemic test after cuff-induced occlusion of the brachial artery. Circulating MP levels in plasma, including levels of endothelial MPs, endothelial progenitor MPs, leukocyte MPs, and platelet MPs, were measured using flow cytometry after staining with cell-specific antibodies. RESULTS: The levels of endothelial MPs, endothelial progenitor MPs, leukocyte MPs, and platelet MPs were significantly different according to the severity of OSA in children. Leukocyte CD11b+ MPs and platelet CD41a+ MPs correlated with the apnea-hypopnea index (AHI) (r = 0.334, P < .001; and r = 0.301, P < .001, respectively), and associations emerged between leukocyte CD11b+ MPs and apolipoprotein B (r = 0.206, P < .05) and between endothelial MPs and low-density lipoprotein cholesterol (r = 0.240, P < .01). In a multivariate regression model, the BMI z score (β ± SE, 0.045 ± 0.020; P = .020) and the CD41a MPs to leukocyte CD45 MPs ratio (β ± SE, 0.074 ± 0.032; P = .021) were independently associated with peak hyperemic responses. After controlling for age, gender, race, BMI z score, and apolipoprotein B levels, endothelial MPs, endothelial progenitor MPs, and leukocyte MPs showed independent associations with the AHI. Complex significant associations emerged between endothelial function, the AHI, and CD41a MPs. CONCLUSIONS: Childhood OSA is associated with higher circulating MP levels that can promote cardiovascular risk. Platelet-derived MPs emerge as being significantly associated with the vascular dysfunction associated with OSA in children and could potentially account for increased risk for altered endothelial function. However, the clinical use of MPs as reliable biomarker indicators of vascular risk will have to await further studies.