Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
J Appl Physiol (1985). 2017 Nov 1;123(5):1047-1054. doi: 10.1152/japplphysiol.00077.2017. Epub 2017 Jun 22.
Intermittent hypoxia (IH) has been implicated in the cardiovascular consequences of obstructive sleep apnea (OSA). However, the lack of suitable experimental systems has precluded assessment as to whether IH is detrimental, protective, or both for the endothelium. The aim of the work was to determine the effects of frequency and amplitude of IH oxygenation swings on aortic endothelial wound healing. Monolayers of human primary endothelial cells were wounded and subjected to constant oxygenation (1%, 4%, 13%, or 20% O) or IH at different frequencies (0.6, 6, or 60 cycles/h) and magnitude ranges (13-4% O or 20-1% O), using a novel well-controlled system, with wound healing being measured after 24 h. Cell monolayer repair was similar at 20% O and 13% O, but was considerably increased (approximately twofold) in constant hypoxia at 4% O The magnitude and frequency of IH considerably modulated wound healing. Cycles ranging 13-4% O at the lowest frequency (0.6 cycles/h) accelerated endothelial wound healing by 102%. However, for IH exposures consisting of 20% to 1% O oscillations, wound closure was reduced compared with oscillation in the 13-4% range (by 74% and 44% at 6 cycles/h and 0.6 cycles/h, respectively). High-frequency IH patterns simulating severe OSA (60 cycles/h) did not significantly modify endothelial wound closure, regardless of the oxygenation cycle amplitude. In conclusion, the frequency and magnitude of hypoxia cycling in IH markedly alter wound healing responses and emerge as key factors determining how cells will respond in OSA. Intermittent hypoxia (IH) induces cardiovascular consequences in obstructive sleep apnea (OSA) patients. However, the vast array of frequencies and severities of IH previously employed in OSA-related experimental studies has led to controversial results on the effects of IH. By employing an optimized IH experimental system here, we provide evidence that the frequency and magnitude of IH markedly alter human aortic endothelial wound healing, emerging as key factors determining how cells respond in OSA.
间歇性低氧 (IH) 与阻塞性睡眠呼吸暂停 (OSA) 的心血管后果有关。然而，缺乏合适的实验系统使得评估 IH 是否对内皮有害、有益或两者兼有变得不可能。本研究的目的是确定 IH 氧合波动的频率和幅度对主动脉内皮伤口愈合的影响。使用一种新的、可精确控制的系统，将单层人原代内皮细胞制成伤口，并在不同频率（0.6、6 或 60 个周期/小时）和幅度范围（13-4% O 或 20-1% O）下进行常氧（1%、4%、13%或 20% O）或 IH，24 小时后测量伤口愈合情况。在 20% O 和 13% O 时，细胞单层修复相似，但在 4% O 的常低氧条件下，修复显著增加（约两倍）。IH 的幅度和频率显著调节伤口愈合。在最低频率（0.6 个周期/小时）下，范围为 13-4% O 的循环加速了内皮伤口愈合 102%。然而，对于由 20%到 1% O 振荡组成的 IH 暴露，与在 13-4%范围内的振荡相比，伤口闭合减少（在 6 个周期/小时和 0.6 个周期/小时时分别减少 74%和 44%）。模拟严重 OSA（60 个周期/小时）的高频 IH 模式不会显著改变内皮伤口闭合，而与氧合循环幅度无关。总之，IH 中低氧循环的频率和幅度显著改变了伤口愈合反应，并成为决定细胞在 OSA 中反应方式的关键因素。间歇性低氧 (IH) 会引起阻塞性睡眠呼吸暂停 (OSA) 患者的心血管后果。然而，以前在 OSA 相关的实验研究中采用的 IH 的频率和严重程度范围广泛，导致 IH 影响的结果存在争议。通过在这里使用优化的 IH 实验系统，我们提供了证据表明 IH 的频率和幅度显著改变了人主动脉内皮的伤口愈合，成为决定细胞在 OSA 中反应方式的关键因素。
