Division of Pulmonary Medicine, Allergy, and Rheumatology, Dept of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Eur Respir J. 2009 Dec;34(6):1390-8. doi: 10.1183/09031936.00009709. Epub 2009 Jul 2.
A sustained elevation of oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) might help to explain their increased risk for cardiovascular diseases. We tested the hypothesis that the values of oxidative stress are increased in otherwise healthy subjects with OSAS when compared with closely matched control subjects. We performed a prospective study of 38 subjects who did not have OSAS and 37 patients with OSAS. Plasma indices of angiotensin (Ang) II, vascular endothelial growth factor (VEGF), oxidised low-density lipoprotein (oxLDL), and circulating endothelial precursor cells (CEPs) were measured in OSAS patients and in matched controls. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups and co-cultured with endothelial cells to examine the effects on tube formation. The OSAS group showed increased levels of Ang II, VEGF, oxLDL and CEPs, which were decreased after nasal continuous positive airway pressure (nCPAP) treatment. In vitro, PBMCs from the OSAS group induced tube formation. Ang II, oxLDL, and Ang II-stimulated PBMCs induced lectin-like oxLDL receptor (LOX-1) expression and VEGF receptor-2 activation on endothelial cells, respectively. These observations suggest an important role of Ang II and oxLDL-mediated LOX-1 upregulation in endothelial cell injury in patients with OSAS.
阻塞性睡眠呼吸暂停综合征(OSAS)患者氧化应激的持续升高可能有助于解释其心血管疾病风险增加。我们检验了这样一个假设,即与匹配的对照相比,OSAS 患者的氧化应激值在其他方面健康的患者中增加。我们对 38 名无 OSAS 的受试者和 37 名 OSAS 患者进行了前瞻性研究。在 OSAS 患者和匹配的对照中测量了血管紧张素(Ang)II、血管内皮生长因子(VEGF)、氧化低密度脂蛋白(oxLDL)和循环内皮祖细胞(CEPs)的血浆指数。从两组中获得外周血单核细胞(PBMC),并与内皮细胞共培养以检查对管形成的影响。OSAS 组表现出 Ang II、VEGF、oxLDL 和 CEPs 水平升高,经鼻持续气道正压通气(nCPAP)治疗后降低。在体外,OSAS 组的 PBMC 诱导管形成。Ang II、oxLDL 和 Ang II 刺激的 PBMC 分别诱导内皮细胞上的凝集素样 oxLDL 受体(LOX-1)表达和 VEGF 受体-2 激活。这些观察结果表明 Ang II 和 oxLDL 介导的 LOX-1 上调在 OSAS 患者的内皮细胞损伤中起重要作用。