Columbia University College of Physicians and Surgeons, Division of Pulmonary, Allergy, and Critical Care Medicine, PH8 Center, Room 101, 630 W 168th St, New York, NY 10032, USA.
Circulation. 2010 Mar 2;121(8):1014-21. doi: 10.1161/CIRCULATIONAHA.109.900357. Epub 2010 Feb 16.
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.
未被识别的阻塞性睡眠呼吸暂停（OSA）在肥胖人群中非常普遍。肥胖和 OSA 均与血管内皮炎症以及心血管疾病风险增加相关。我们直接研究了这些通常归因于肥胖的内皮改变是否与 OSA 有关。
71 名受试者的 BMI 从正常到肥胖，均接受了多导睡眠图监测。为了直接评估血管炎症和氧化应激，我们通过免疫荧光法检测了新采集的静脉内皮细胞中核因子-κB 和硝基酪氨酸的表达。为了评估内皮一氧化氮（NO）的基础产生和活性，我们检测了内皮型一氧化氮合酶（eNOS）和磷酸化 eNOS 的表达。通过肱动脉血流介导的扩张来测量血管反应性。eNOS 和磷酸化 eNOS 的表达以及血流介导的扩张在 OSA 患者（n=38）中明显低于 OSA 无患者（n=33），而硝基酪氨酸的表达在 OSA 患者中明显高于 OSA 无患者，无论中心性肥胖如何。肥胖的 OSA 患者中核因子-κB 的表达高于肥胖的 OSA 无患者（P=0.004）。在 OSA 患者和 OSA 无患者中，BMI 或中心性肥胖的增加并没有显著影响蛋白表达和血流介导的扩张。在接受持续气道正压通气治疗 4 周后，坚持每天持续气道正压通气>4 小时的 OSA 患者的血流介导的扩张以及 eNOS 和磷酸化 eNOS 的表达明显增加，而硝基酪氨酸和核因子-κB 的表达明显降低。
未经治疗的 OSA 而不是肥胖，是肥胖患者血管内皮功能障碍、炎症和氧化应激增加的主要决定因素。
