School of Basic Medical Sciences, and The Second Affiliated Hospital of Shandong First Medical University & Shandong Academy of Medical Science, Jinan, China (X.L., Y.C., X.X., C.W., X.L., C.Y., Z.Z., G.S.).
Hydrogen medicine center, Tai 'an City Central Hospital, China (Q.N.).
Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):995-1014. doi: 10.1161/ATVBAHA.123.319026. Epub 2023 Apr 6.
Insufficient or disrupted sleep increases the risk of cardiovascular disease, including atherosclerosis. However, we know little about the molecular mechanisms by which sleep modulates atherogenesis. This study aimed to explore the potential role of circulating exosomes in endothelial inflammation and atherogenesis under sleep deprivation status and the molecular mechanisms involved.
Circulating exosomes were isolated from the plasma of volunteers with or without sleep deprivation and mice subjected to 12-week sleep deprivation or control littermates. miRNA array was performed to determine changes in miRNA expression in circulating exosomes.
Although the total circulating exosome levels did not change significantly, the isolated plasma exosomes from sleep-deprived mice or human were a potent inducer of endothelial inflammation and atherogenesis. Through profiling and functional analysis of the global microRNA in the exosomes, we found miR-182-5p is a key exosomal cargo that mediates the proinflammatory effects of exosomes by upregulation of MYD88 (myeloid differentiation factor 88) and activation of NF-ĸB (nuclear factor kappa-B)/NLRP3 pathway in endothelial cells. Moreover, sleep deprivation or the reduction of melatonin directly decreased the synthesis of miR-182-5p and led to the accumulation of reactive oxygen species in small intestinal epithelium.
The findings illustrate an important role for circulating exosomes in distant communications, suggesting a new mechanism underlying the link between sleep disorder and cardiovascular disease.
睡眠不足或睡眠质量差会增加心血管疾病（包括动脉粥样硬化）的风险。然而，我们对睡眠调节动脉粥样硬化形成的分子机制知之甚少。本研究旨在探讨在睡眠剥夺状态下循环外泌体在血管内皮炎症和动脉粥样硬化形成中的潜在作用及其相关的分子机制。
从睡眠剥夺志愿者或无睡眠剥夺志愿者以及接受 12 周睡眠剥夺或对照同窝仔鼠的血浆中分离循环外泌体。通过 miRNA 芯片检测循环外泌体中 miRNA 表达的变化。
尽管总循环外泌体水平没有显著变化，但来自睡眠剥夺小鼠或人类的分离血浆外泌体是内皮炎症和动脉粥样硬化形成的有力诱导物。通过对 exosomes 中全局 microRNA 的分析和功能分析，我们发现 miR-182-5p 是一种关键的外泌体货物，通过上调 MYD88（髓样分化因子 88）和激活 NF-κB（核因子 kappa-B）/NLRP3 通路，在血管内皮细胞中介导外泌体的促炎作用。此外，睡眠剥夺或褪黑素的减少直接降低了 miR-182-5p 的合成，并导致小肠上皮细胞中活性氧的积累。
这些发现说明了循环外泌体在远程通讯中的重要作用，提示了睡眠障碍与心血管疾病之间联系的新机制。
