title: Nitric oxide production by monocytes in children with OSA and endothelial dysfunction.
abstract: OSA (obstructive sleep apnoea) is associated with a higher risk for alterations in post-occlusive hyperaemia, an eNOS (endothelial NO synthase)-dependent endothelial response. However, since not all children manifest endothelial dysfunction, we hypothesized that differences in circulating monocyte subsets and NO production may underlie the vascular phenotype in paediatric OSA. Matched pre-pubertal children with OSA with abnormal endothelial function (OSAab) and with normal endothelial function (OSAn), and controls (CO) were recruited. Peripheral blood mononuclear cells were subtyped into CD14+ and CD16+ cells, and NO production was assessed using flow cytometry. Endothelial dysfunction was defined as Tmax (time to reach maximal reperfusion)>45 s by laser Doppler flowmetry. A total of 11 OSAab, 12 OSAn and 12 CO-matched children completed the study. The OSAab group had increased CD16+ and decreased CD14+ cell numbers. They also had increased CX3CR1 (CX3C chemokine receptor 1) expression in CD16+ monocytes (P<0.01). Furthermore, monocytes from the OSAab group exhibited overall reduced NO production (787±71 compared with 1226±229 and 1089±116 median fluorescence intensity in the OSAn group and CO children respectively; P<0.01). Significant bivariate associations emerged between NO production, monocyte subsets, CX3CR1 in CD16+ monocytes, the CD14+/CD16+ ratio and Tmax. Thus OSA in children is associated with increased numbers of pro-inflammatory monocytes and reduced NO production in circulating monocytes that are closely associated with endothelial function.
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: †Flow Cytometry Core Facility, Pritzker School of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Duggan
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Sindhuja
authors.initials: S
authors.lastname: Harshan Vardhan
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Hui-Leng
authors.initials: HL
authors.lastname: Tan
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Helena
authors.initials: H
authors.lastname: Molero Ramirez
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhattacharjee
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: Hari P R
authors.initials: HP
authors.lastname: Bandla
authors.affiliation: *Section of Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, IL 60637, U.S.A.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*
chemical_list: D009569:Nitric Oxide