One night of sleep deprivation induces release of small extracellular vesicles into circulation and promotes platelet activation by small EVs

Abstract

Extracellular vesicles (EVs) are emerging as key players in intercellular communication. Few studies have focused on EV levels in subjects with sleep disorders. Here, we aimed to explore the role of acute sleep deprivation on the quantity and functionality of circulating EVs, and their tissue distribution. EVs were isolated by ultracentrifugation from the plasma of volunteers and animals undergoing one night of sleep deprivation. Arterio‐venous shunt, FeCl3 thrombus test and thrombin‐induced platelet aggregation assay were conducted to evaluate the in vivo and in vitro bioactivity of small EVs. Western blotting was performed to measure the expression of EV proteins. The fate and distribution of circulating small EVs were determined by intravital imaging. We found that one night of sleep deprivation triggers release of small EVs into the circulation in both healthy individuals and animals. Injection of sleep deprivation‐liberated small EVs into animals increased thrombus formation and weight in thrombosis models. Also, sleep deprivation‐liberated small EVs promoted platelet aggregation induced by thrombin. Mechanistically, sleep deprivation increased the levels of HMGB1 protein in small EVs, which play important roles in platelet activation. Furthermore, we found sleep deprivation‐liberated small EVs are more readily localize in the liver. These data suggested that one night of sleep deprivation is a stress for small EV release, and small EVs released here may increase the risk of thrombosis. Further, small EVs may be implicated in long distance signalling during sleep deprivation‐mediated adaptation processes.

Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes

“…This view originates mainly from studies in which the synthetic HMGB1 protein was directly applied to the culture medium of various cells [ 1 , 74 , 75 ]. However, if HMGB1 is released within EVs in vivo as previously predicted [ 2 , 76 ] and shown in the present study, binding to intracellular counterparts of these receptors is more likely after uptake. The width of the interstitium around cell bodies ranges from 38 to 64 nm in the rat brain, smaller than most sEVs, creating an optimal environment for sEVs released to directly contact the large astrocyte membrane surface, ensheathing neuron soma [ 77 ] at the moment they are released, which may also be facilitated with more specific uptake mechanisms [ 71 ].…”

Circadian Regulation of the Lactate Metabolic Kinetics in Mice Using the [1H-13C]-NMR Technique

“…Our research found that after acute 12-hour sleep deprivation, liver metabolism was strongly activated, with heightened catabolic activity and a signi cant increase in various metabolites. Previous studies suggest that a single 6-hour episode or a full night of acute sleep deprivation induces abnormal glucose tolerance, liver insulin resistance [30] and increased risk of thrombosis [31]. Consequently, our results raise a cautionary note for individuals who habitually stay up late, as such behavior not only induces signi cant uctuations in various liver metabolic indicators but also harbors potential detrimental impacts on physical well-being and brain functionality.…”

Assessment of circulating extracellular vesicles from calorie‐restricted mice and humans in ischaemic injury models

“…However, this short duration is a limitation of our study. Changes in EV properties can be initiated quickly, such as after acute injury or with one night of sleep deprivation (Luo et al., 2023 ; Wang et al., 2022 ). However, we speculate that a longer fasting period (under appropriate clinical supervision) would allow more time for the circulating EV pool to be turned over.…”

“…EVs derived from mouse hearts after MI induction promoted pro‐inflammatory behaviour, influenced macrophage polarisation, and aggravated heart injury in recipient mice (Ge et al., 2021 ). In another study, one night of sleep deprivation (in mice) altered circulating EVs to have more pro‐thrombotic effects (Wang et al., 2022 ). Exercise has been shown (in mice) promote mobilisation of EVs from brown adipose tissue which contained cardioprotective miRNAs (Zhao et al., 2022 ).…”