Vascular inflammation in obesity and sleep apnea.

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 endothelial alterations that are commonly attributed to obesity are in fact related to OSA. Seventy-one subjects with body mass index (BMI) ranging from normal to obese underwent attended polysomnography. To assess directly vascular inflammation and oxidative stress, we quantified expression of nuclear factor kappa B (NFκB) and nitrotyrosine by immunofluorescence in freshly harvested venous endothelial cells. To evaluate basal endothelial nitric oxide (NO) production and activity, we quantified expression of endothelial NO synthase (eNOS) and phosphorylated eNOS (P-eNOS). Vascular reactivity was measured by brachial artery flow-mediated dilation (FMD). Expression of eNOS and P-eNOS and FMD 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 NFκB was greater in obese OSA patients than in obese OSA-free subjects (p=0.004). Protein expression and FMD were not significantly affected by increasing BMI or central obesity in OSA patients and in OSA-free subjects. After 4 weeks of continuous positive airway pressure (CPAP) therapy, FMD and expression of eNOS and P-eNOS significantly increased whereas expression of nitrotyrosine and NFκB significantly decreased in OSA patients who adhered with CPAP≥4 hours daily. Untreated OSA rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation and elevated oxidative stress in obese patients.

在肥胖症中，未被识别的阻塞性睡眠呼吸暂停（OSA）非常普遍。肥胖和OSA都与血管内皮炎症以及心血管疾病风险增加有关。我们直接研究了通常归因于肥胖的内皮改变实际上是否与OSA有关。 71名体重指数（BMI）从正常到肥胖的受试者接受了多导睡眠监测。为了直接评估血管炎症和氧化应激，我们通过免疫荧光法对新鲜采集的静脉内皮细胞中核因子κB（NFκB）和硝基酪氨酸的表达进行了定量。为了评估基础内皮一氧化氮（NO）的产生和活性，我们对内皮一氧化氮合酶（eNOS）和磷酸化内皮一氧化氮合酶（P - eNOS）的表达进行了定量。通过肱动脉血流介导的舒张（FMD）来测量血管反应性。无论中心性肥胖与否，OSA患者（n = 38）中eNOS和P - eNOS的表达以及FMD显著低于无OSA的受试者（n = 33），而硝基酪氨酸的表达则显著更高。肥胖的OSA患者中NFκB的表达高于肥胖的无OSA受试者（p = 0.004）。在OSA患者和无OSA的受试者中，蛋白质表达和FMD不受BMI增加或中心性肥胖的显著影响。经过4周的持续气道正压通气（CPAP）治疗后，每天坚持使用CPAP≥4小时的OSA患者中，FMD以及eNOS和P - eNOS的表达显著增加，而硝基酪氨酸和NFκB的表达显著降低。 在肥胖患者中，未经治疗的OSA而非肥胖是血管内皮功能障碍、炎症和氧化应激升高的主要决定因素。