8-epi-prostaglandin-f2alpha and Sleep-Apnea-Syndromes

Oxidative stress plays a crucial role in impairing endothelial function in sleep disordered breathing (SDB) but the underlying mechanism is still undefined. The objective of this study was to evaluate the interplay between oxidative stress, assessed by serum isoprostanes (8-iso-PGF2α) and soluble NOX2-dp (sNOX2-dp), and endothelial function, assessed by flow-mediated dilation (FMD), in children with SDB and healthy controls (HC).. One-hundred forty-four children including 45 with primary snoring (PS), 22 with obstructive sleep apnea (OSA) and 67 HC were recruited in this study; in 15 out of 22 OSA children FMD, serum 8-iso-PGF2α and sNOX2-dp were assessed before and after one month post adeno-tonsillectomy (AT).. Compared with HC, OSA and PS children had significantly higher sNOX2-dp and serum 8-iso-PGF2α levels and lower FMD; compared with PS, FMD was significantly lower in OSA children. No significant difference for sNOX2-dp and serum 8-iso-PGF2α was observed between OSA and PS children. FMD was inversely correlated with sNOX2-dp levels (p<0.001) and with serum 8-iso-PGF2α (p<0.001). In multiple linear regression analysis, sNOX2-dp (p<0.001) and serum 8-iso-PGF2α (p<0.001) were the only independent predictive variables associated with FMD. AT significantly decreased sNOX2-dp and serum 8-iso-PGF2α levels (from 38.2±8.8 to 22.4±11.1 pg/ml, p<0.001, and from 281.4±69.7 to 226.0±66.4 pg/ml, p<0.001, respectively); conversely, FMD significantly increased after AT in OSA children (from 3.0±1.5 to 8.0±2.8%, p<0.001).. This study suggests that NOX2-derived oxidative stress is involved in artery dysfunction in SDB children. Such hypothesis is reinforced by FMD improvement after AT coincidentally with oxidative stress lowering.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167.

Topics: Adenoidectomy; Age Factors; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Dinoprost; Endothelium, Vascular; Female; Humans; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Rome; Signal Transduction; Sleep Apnea Syndromes; Time Factors; Tonsillectomy; Treatment Outcome

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F(2t)-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F(2t)-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima-media thickness (IMT). Urinary 15-F(2t)-isoprostanes were measured by liquid chromatography-tandem mass spectrometry. Urinary 15-F(2t)-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2+/-7.3 vs 12.3+/-2.8 ng/mmol creatinine; P=0.020). Mean carotid IMT was correlated with 15-F(2t)-isoprostane (r=0.532; P<0.001) and with the apnea-hypopnea index (r=0.345; P=0.029). 15-F(2t)-Isoprostane level was related to the night time spent at SaO(2)<90% (r=0.478; P=0.002), the apnea-hypopnea index (r=0.465; P=0.003), and the mean nocturnal SaO(2) (r=-0.424; P=0.007). These results showed a relationship between lipid peroxidation, carotid intima-media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process.

Topics: Adult; Atherosclerosis; Blood Pressure; Creatinine; Dinoprost; Female; Humans; Hypoxia; Isoprostanes; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Oxygen; Polysomnography; Sleep Apnea Syndromes; Tunica Intima; Tunica Media