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Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea.

ABSTRACT: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. We hypothesized that patients with OSA and no cardiovascular disease have oxidant-related microcirculatory endothelial dysfunction.To evaluate the microcirculation in OSA.This study included seven patients with OSA and seven age- and weight-matched control subjects (mean age, 38 yr; mean body mass index, 32.5 kg/m²). All participants were free of cardiovascular risk factors. Participants received measurement of brachial artery flow-mediated dilation and forearm subcutaneous biopsy. Patients underwent repeated tests 12 weeks after treatment. Microcirculatory endothelial cells were isolated, and immunohistochemistry staining for peroxynitrite in the microcirculation was performed.Flow-mediated dilation was lower in patients than in control subjects at baseline (mean ± SEM: 5.7 ± 0.5 vs. 9.5 ± 0.6; P = 0.02) and increased after treatment (5.7-7.3; change, 1.7 ± 0.6; P = 0.04). Microcirculatory peroxynitrite deposit was higher in patients compared with control subjects (44.0 ± 1.6 vs. 21.8 ± 1.9 stain density units; P < 0.001) and decreased after treatment from 44.0 to 30.5 stain density units (change, -13.5 ± 2.9; P = 0.009). In patients, transcription of endothelial nitric oxide synthase decreased from 5.2 to -1.3 after treatment (change, 6.5 ± 2.5; P = 0.05), and transcription of superoxide dismutase1 decreased from -4.0 to -12.3 after treatment (change, -8.3 ± 2.1; P = 0.01). These changes persisted after adjustment for weight and underlying severity of OSA.This is the first direct evaluation of the microcirculation in OSA. Patients with OSA with low cardiovascular risk status had increased oxidant production in the microcirculation and endothelial dysfunction, both of which improved with treatment. Endothelial nitric oxide synthase transcription decreased with treatment.

SUBMITTER: Patt BT

PROVIDER: S-EPMC3029939 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea.

Patt Brian T BT Jarjoura David D Haddad Diane N DN Sen Chandan K CK Roy Sashwati S Flavahan Nicholas A NA Khayat Rami N RN

American journal of respiratory and critical care medicine 20100723 12

<h4>Rationale</h4>Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. We hypothesized that patients with OSA and no cardiovascular disease have oxidant-related microcirculatory endothelial dysfunction.<h4>Objectives</h4>To evaluate the microcirculation in OSA.<h4>Methods</h4>This study included seven patients with OSA and seven age- and weight-matched control subjects (mean age, 38 yr; mean body mass index, 32.5 kg/m²). All participants were free of cardiovascular risk fac ...[more]

PMID: 20656942

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Project description:BackgroundObstructive sleep apnea (OSA) is a common and severe social problem. Erectile dysfunction (ED) is an important health concern. The prevalence of OSA with ED is increasing, which significantly affects the quality of life and work efficiency of patients. However, the mechanism underlying the comorbidity of these two diseases remains unclear.Objectives(1) Investigate the prevalence of OSA with ED; (2) analyze the correlation between OSA and ED; and (3) explore the treatment response to and possible mechanism of uvulapalatopharyngoplasty (UPPP) in patients with OSA and ED. This study aims to provide a theoretical basis for the clinical diagnosis and comprehensive treatment of OSA with ED and improve prevention and treatment strategies.Materials and methodsIn total, 135 subjects were enrolled in the study. Clinical data, polysomnography, the ESS score, Beck anxiety score, Beck depression score, IIEF-5 score and ASEX score were recorded before UPPP and 6 months after UPPP. Sex hormones were measured for all subjects using a Roche electrochemiluminescence analyzer.ResultThe prevalence of OSA with ED was 64.52%, and the prevalence of severe OSA with ED was 73.02%. The prevalence of OSA with ED increased with age, BMI and apnea-hypopnea index (AHI) value. Among polysomnography indicators, minimum oxygen saturation and average oxygen saturation may predict the occurrence of OSA with ED. Improving the patient's anxiety and depression is very important for treating OSA with ED. Sex hormone levels were not significantly correlated with the occurrence of OSA with ED.ConclusionED is a common symptom of OSA patients. This study showed that sex hormone levels in OSA patients with ED were not significantly correlated with the condition, but further investigation of this relationship is worthwhile. It is recommended that the free and combined types of sex hormones be further distinguished during testing because the free type is the active form. UPPP surgical treatment is effective for OSA with ED, and its possible mechanism is protection of the peripheral nerves of the sex organs by improving nighttime hypoxia and arousal.

Project description:Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, and atherosclerosis. We observed a correlation between microcirculatory reactivity and endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that OSA affects (micro)vasculature and we aimed to identify vascular gene targets of OSA that could possibly serve as reliable biomarkers of severity of the disease and possibly of vascular risk. Using quantitative RT-PCR, we evaluated gene expression in skin biopsies of OSA patients, mouse aortas from animals exposed to 4-week intermittent hypoxia (IH; rapid oscillations in oxygen desaturation and reoxygenation), and human dermal microvascular (HMVEC) and coronary artery endothelial cells (HCAEC) cultured under IH. We demonstrate a significant upregulation of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha-induced protein 3 (TNFAIP3; A20), hypoxia-inducible factor 1 alpha (HIF-1??? and vascular endothelial growth factor (VEGF) expression in skin biopsies obtained from OSA patients with severe nocturnal hypoxemia (nadir saturated oxygen levels [SaO2]<75%) compared to mildly hypoxemic OSA patients (SaO2 75%-90%) and a significant upregulation of vascular cell adhesion molecule 1 (VCAM-1) expression compared to control subjects. Gene expression profile in aortas of mice exposed to IH demonstrated a significant upregulation of eNOS and VEGF. In an in vitro model of OSA, IH increased expression of A20 and decreased eNOS and HIF-1? expression in HMVEC, while increased A20, VCAM-1 and HIF-1?expression in HCAEC, indicating that EC in culture originating from distinct vascular beds respond differently to IH stress. We conclude that gene expression profiles in skin of OSA patients may correlate with disease severity and, if validated by further studies, could possibly predict vascular risk in OSA patients.

Project description:BackgroundObstructive sleep apnea (OSA) is a highly prevalent disorder that has been associated with an increased risk for cardiovascular morbidity, even in children. However, not all children with OSA manifest alterations in endothelial postocclusive hyperemia, an endothelial nitric oxide synthase (eNOS)-dependent response. Since expression of the eNOS gene is regulated by epigenetic mechanisms and OSA may cause epigenetic modifications such as DNA hypermethylation, we hypothesized that epigenetic modifications in the eNOS gene may underlie the differential vascular phenotypes in pediatric OSA.MethodsAge-, sex-, ethnicity-, and BMI-matched prepubertal children with polysomnographically confirmed OSA and either normal (OSAn) or abnormal (OSAab) postocclusive hyperemic responses, assessed as the time to attain peak reperfusion flow (Tmax) by laser Doppler flowmetry, were recruited. Blood genomic DNA was assessed for epigenetic modifications in the eNOS gene using pyrosequencing. Children with no evidence of OSA or endothelial dysfunction served as a control group.ResultsThe study comprised 36 children with OSA (11 with OSAab and 25 with OSAn) and 35 children in the control group. Overall, the mean age was 7.5 ± 2.4 years, 65% were boys, and 30% were obese; mean apnea-hypopnea index was 18 ± 8.6/h of sleep for the children with OSA. Tmax was 66.7 ± 8.8 s in the OSAab group and 30.1 ± 8.3 s in the OSAn group (P < .001). Pyrosequencing of the proximal promoter region of the eNOS gene revealed no significant differences in six of the seven CpG sites. However, a CpG site located at position -171 (relative to transcription start site), approximating important transcriptional elements, displayed significantly higher methylation levels in the OSAab group as compared with the OSAn or control groups (81.5% ± 3.5%, 74.8% ± 1.4%, and 74.5% ± 1.7%, respectively; P < .001). eNOS mRNA expression levels were assessed in a separate group of children and were significantly reduced in the OSAab group in comparison with the OSAn group.ConclusionsThe presence of abnormal eNOS-dependent vascular responses in children with OSA is associated with epigenetic modifications in the eNOS gene.

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Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea.

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Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea.

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