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Molecular biomarkers of vascular dysfunction in obstructive sleep apnea.

ABSTRACT: 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.

SUBMITTER: Kaczmarek E

PROVIDER: S-EPMC3726633 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Molecular biomarkers of vascular dysfunction in obstructive sleep apnea.

Kaczmarek Elzbieta E Bakker Jessie P JP Clarke Douglas N DN Csizmadia Eva E Kocher Olivier O Veves Aristidis A Tecilazich Francesco F O'Donnell Christopher P CP Ferran Christiane C Malhotra Atul A

PloS one 20130729 7

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 dis ...[more]

PMID: 23923005

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Project description:BackgroundObstructive sleep apnea (OSA) is an independent risk factor for the development of cardiovascular diseases. Aim of this present study was to evaluate and extend recent research on the influence of obstructive sleep apnea on vascular strain.MethodsA total number of 98 patients were integrated in the study. Patients were grouped according to the Apnea-Hypopnea-Index (AHI) in patients with mild-to-moderate OSA (5/h ≤ AHI < 30/h), severe OSA (AHI ≥ 30/h) and controls (AHI < 5/h). Groups were matched in age, body-mass-index and cardiovascular risks. Vascular strain of common carotid arteries was assessed by ultrasound speckle-tracking. A minor group of 30 patients and controls further underwent assessment of vascular strain of brachial and femoral arteries. Additionally, all patients underwent blood testing to reveal potential influences of inflammatory markers on arterial stiffness. In additional analysis we examined the effect of statin therapy on vascular strain.ResultsPatients with OSA showed significantly reduced values of vascular strain of common carotid arteries. Radial and circumferential strains were significantly lower in both patients with mild-to-moderate (p = .05) and patients with severe OSA (p = .001) compared to control. Vascular strain parameters of brachial and femoral arteries showed no consistent results. There were no significant correlations of inflammatory markers with vascular strain parameters. No significant differences in vascular strain were detected between statin and non-statin groups.ConclusionPatients with OSA show significantly reduced vascular strain assessed by ultrasound-based speckle-tracking. Vascular stiffness increases with the severity of the disease. Target vessels to assess vascular strain in patients with OSA are common carotid arteries, whereas other sites of the arterial tree are not reliable. No significant impact of current statin therapy on vascular strain was found. Further studies are needed to evaluate potential benefit of statins in secondary prevention of atherosclerosis in OSA.

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.

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Molecular biomarkers of vascular dysfunction in obstructive sleep apnea.

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Molecular biomarkers of vascular dysfunction in obstructive sleep apnea.

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