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.
Nitric oxide production by monocytes in children with OSA and endothelial dysfunction
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Leila Kheirandish-Gozal, Yang Wang, Ryan C. Duggan, Sindhuja Harshan Vardhan, Hui-Leng Tan, Helena Molero Ramirez, Abdelnaby Khalyfa, Rakesh Bhattacharjee, Hari P.R. Bandla, David Gozal; Nitric oxide production by monocytes in children with OSA and endothelial dysfunction. Clin Sci (Lond) 1 September 2014; 127 (5): 323–330. doi: https://doi.org/10.1042/CS20130679
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