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Vascular inflammation in obesity and sleep apnea.

ABSTRACT: Unrecognized obstructive sleep apnea (OSA) is highly prevalent in obesity. Both obesity and OSA are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. We investigated directly whether the endothelial alterations that are attributed commonly to obesity are in fact related to OSA.Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular inflammation and oxidative stress directly, we quantified the expression of nuclear factor-kappaB and nitrotyrosine by immunofluorescence in freshly harvested venous endothelial cells. To evaluate basal endothelial nitric oxide (NO) production and activity, we quantified the expression of endothelial NO synthase (eNOS) and phosphorylated eNOS. Vascular reactivity was measured by brachial artery flow-mediated dilation. Expression of eNOS and phosphorylated eNOS and flow-mediated dilation were significantly lower, whereas expression of nitrotyrosine was significantly greater in OSA patients (n=38) than in OSA-free subjects (n=33) regardless of central adiposity. Expression of nuclear factor-kappaB was greater in obese OSA patients than in obese OSA-free subjects (P=0.004). Protein expression and flow-mediated dilation were not significantly affected by increasing body mass index or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure therapy, flow-mediated dilation and expression of eNOS and phosphorylated eNOS significantly increased whereas expression of nitrotyrosine and nuclear factor-kappaB significantly decreased in OSA patients who adhered to continuous positive airway pressure >/=4 hours daily.Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients.

SUBMITTER: Jelic S

PROVIDER: S-EPMC2864627 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Vascular inflammation in obesity and sleep apnea.

Jelic Sanja S Lederer David J DJ Adams Tessa T Padeletti Margherita M Colombo Paolo C PC Factor Phillip H PH Le Jemtel Thierry H TH

Circulation 20100216 8

<h4>Background</h4>Unrecognized obstructive sleep apnea (OSA) is highly prevalent in obesity. Both obesity and OSA are associated with vascular endothelial inflammation and increased risk for cardiovascular diseases. We investigated directly whether the endothelial alterations that are attributed commonly to obesity are in fact related to OSA.<h4>Methods and results</h4>Seventy-one subjects with a body mass index ranging from normal to obese underwent attended polysomnography. To assess vascular ...[more]

PMID: 20159829

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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 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.

Dataset Information

Vascular inflammation in obesity and sleep apnea.

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Vascular inflammation in obesity and sleep apnea.

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