INSERM U771, Centre National de la Recherche Scientifique UMR 6214, Université d'Angers, Angers, France.
Am J Pathol. 2010 Aug;177(2):974-83. doi: 10.2353/ajpath.2010.091252. Epub 2010 Jun 21.
Endothelial dysfunction is involved in vascular complications of obstructive sleep apnea (OSA). In this study, circulating microparticles (MPs) from patients with OSA-induced nocturnal desaturations were characterized and their effects on endothelial function were evaluated. Two age-matched groups of patients undergoing polysomnography for OSA were compared: 35 desaturators with a 3% oxyhemoglobin desaturation index (ODI) > or = 10 events per hour of sleep and 27 nondesaturators with ODI <10 events per hour. MPs were characterized by flow cytometry and then either used to treat in vitro human endothelial cells or to study endothelial function in mice. Circulating MPs did not differ between groups, but MPs from granulocytes and activated leukocytes (CD62L(+)) were found at higher levels in desaturators. In vitro, MPs from desaturators reduced endothelial nitric oxide (NO) production by enhancing phosphorylation of endothelial NO synthase at the site of inhibition and expression of caveolin-1. CD62L(+) MPs positively correlated with ODI. Endothelial NO production negatively correlated with both CD62L(+) MPs and ODI. MPs from desaturators increased expression of endothelial adhesion molecules including E-selectin, ICAM-1 and ITGA5, and cyclooxygenase 2. Moreover, injection of MPs from desaturators into mice impaired endothelium-dependent relaxation in aorta and flow-induced dilation in small mesenteric arteries. This study demonstrates an association between endothelial dysfunction and increased circulating levels of CD62L(+) MPs. This may initiate atherogenic processes in patients with OSA and severe nighttime hypoxia.
内皮功能障碍与阻塞性睡眠呼吸暂停（OSA）的血管并发症有关。在这项研究中，我们对 OSA 引起的夜间低氧血症患者的循环微颗粒（MPs）进行了特征描述，并评估了它们对内皮功能的影响。我们比较了两组接受多导睡眠图检查的 OSA 患者：35 名低氧血症患者，其 3%氧合血红蛋白低氧饱和度指数（ODI）>或=每小时睡眠 10 次事件；27 名非低氧血症患者，ODI<每小时睡眠 10 次事件。通过流式细胞术对 MPs 进行了特征描述，然后将其用于体外人内皮细胞治疗或研究小鼠的内皮功能。两组之间循环 MPs 无差异，但在低氧血症患者中发现来自粒细胞和活化白细胞（CD62L(+）的 MPs 水平较高。在体外，低氧血症患者的 MPs 通过增强内皮型一氧化氮合酶（eNOS）抑制部位的磷酸化和小窝蛋白-1 的表达，减少内皮一氧化氮（NO）的产生。CD62L(+) MPs 与 ODI 呈正相关。内皮 NO 产生与 CD62L(+) MPs 和 ODI 均呈负相关。低氧血症患者的 MPs 增加了内皮黏附分子的表达，包括 E-选择素、ICAM-1 和 ITGA5，以及环氧化酶 2。此外，向低氧血症患者的 MPs 注射到小鼠体内，会损害主动脉内皮依赖性松弛和小肠系膜动脉血流诱导扩张。本研究表明，内皮功能障碍与循环中 CD62L(+) MPs 水平升高有关。这可能会引发 OSA 患者和严重夜间低氧血症患者的动脉粥样硬化过程。
