Uptake of oxidative stress-mediated extracellular vesicles by vascular endothelial cells under low magnitude shear stress

Xian, Qiming; Zhang, Kun; Qiu, Juhui; Wang, Nan; Qu, Kai; Cui, Yuliang; Huang, Junli; Luo, Li; Zhong, Yuan; Tian, Tian; Wu, Wei; Wang, Yi; Wang, Guixue

doi:10.1016/j.bioactmat.2021.10.038

Cited by 25 publications

(28 citation statements)

References 56 publications

(59 reference statements)

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“…The copyright holder for this preprint this version posted January 2, 2023. ; https://doi.org/10.1101/2022.12.31.522373 doi: bioRxiv preprint derived EVs, as well as polystyrene or gold nanoparticles (Charwat et al, 2018;Qin et al, 2021). This suggests that the uptake of various types of particles is enhanced by low magnitude shear stress, and implies that atheroprone regions of the arterial tree may be targetable by therapeutic nanovesicles.…”

Section: Discussionmentioning

confidence: 99%

Atheroprone shear stress stimulates noxious endothelial extracellular vesicle uptake by MCAM and PECAM-1 cell adhesion molecules

Coly

Mezine

et al. 2023

Preprint

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Atherosclerotic lesions mainly form in arterial areas exposed to low shear stress (LSS), where endothelial cells express a senescent and inflammatory phenotype. Conversely, high shear stress (HSS) has atheroprotective effects on the endothelium. Endothelial cell-derived extracellular vesicles have been shown to regulate inflammation, senescence and angiogenesis and therefore play a crucial role in vascular homeostasis and disease. While previous studies have shown links between hemodynamic forces and extracellular vesicle release, the exact consequences of shear stress on the release and uptake of endothelial EVs remains elusive. Our aim is therefore to decipher the interplay between these processes in endothelial cells exposed to atheroprone or atheroprotective shear stress. Confluent human umbilical vein endothelial cells (HUVEC) were exposed to either LSS or HSS for 24 hours. Large and small EVs were isolated from conditioned medium by sequential centrifugation and size exclusion chromatography. They were characterized by TEM, Western blot analysis of EV markers, tunable resistive pulse sensing, flow cytometry and proteomics. Uptake experiments were performed using fluorescently-labeled EVs and differences between groups were assessed by flow cytometry and confocal microscopy. We found that levels of large and small EVs in HUVEC conditioned media were fifty and five times higher in HSS than in LSS conditions, respectively. In vivo and in vitro uptake experiments revealed greater EV incorporation by cells exposed to LSS conditions compared to HSS. Additionally, endothelial LSS-EVs appeared to have a greater affinity for HUVECs than HSS-EVs or EVs derived from platelets, red blood cells, granulocytes and peripheral blood mononuclear cells. Proteomic analysis revealed that LSS-EVs were enriched in adhesion proteins such as PECAM1, MCAM, which were involved in EV uptake by endothelial cells. LSS-EVs also carried mitochondrial material, which may be involved in elevating reactive oxygen species levels in recipient cells. These findings suggest that endothelial shear stress has a significant impact during EV biogenesis and uptake. Given the major role of EVs and shear stress in vascular health, deciphering the relation between these processes may yield innovative strategies for the early detection and treatment of endothelial dysfunction.

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Section: Discussionmentioning

confidence: 99%

Atheroprone shear stress stimulates noxious endothelial extracellular vesicle uptake by MCAM and PECAM-1 cell adhesion molecules

Coly

Mezine

et al. 2023

Preprint

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“…Recent research has created newly mimic exosomes, which combine synthetic liposome and macrophage-derived EVs to enhance drug delivery efficiency [ 156 ]. Furthermore, our recent researches find that synthetic RBC-derived sEVs can prolong circulating time, significantly attenuate the progression of atherosclerosis [ 71 ] and specifically be enriched in low shear stress area [ 157 ]. Moreover, synthetic EVs can also be modified to construct targeting structures on the membrane surface via genetic engineering and chemical conjunction [ 158 , 159 ].…”

Section: Discussionmentioning

confidence: 99%

Recent advances of natural and bioengineered extracellular vesicles and their application in vascular regeneration

Wang

Chen

et al. 2022

Regenerative Biomaterials

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The progression of cardiovascular diseases such as atherosclerosis and myocardial infarction leads to serious vascular injury, highlighting the urgent need for targeted regenerative therapy. Extracellular vesicles (EVs) composed of a lipid bilayer containing nuclear and cytosolic materials are relevant to the progression of cardiovascular diseases. Moreover, EVs from multiple cells will deliver bioactive cargo in pathological cardiovascular and regulate the biological function of recipient cells, such as inflammation, proliferation, angiogenesis, and polarization. However, because the targeting and bioactivity of natural EVs are subject to several limitations, bioengineered EVs have achieved wide advancements in biomedicine. Bioengineered EVs involve three main ways to acquire including 1) Modification of the EVs after isolation; 2) Modification of producer cells before EVs’ isolation; 3) Synthesize EVs using natural or modified cell membranes, and encapsulating drugs or bioactive molecules into EVs. In this review, we firstly summarize the cardiovascular injury-related disease and describe the role of different cells and EVs in vascular regeneration. We also discuss the application of bioengineered EVs from different producer cells to cardiovascular diseases. Finally, we summarize the molecular that can be modified in EVs to specifically target abnormal cells in injured vascular.

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“…211 In monocytes, flow-induced activation was shown to be regulated by ROS signaling, 212 and upon activation by low fluid shear stress, these cells differentiated into inflammatory macrophages when investigated in a renal fluid shear model. 146 Interestingly, Qin et al 213 recently demonstrated that low fluid shear stress facilitated the phagocytosis of EVs by vascular endothelial cells in vitro and in vivo and suggested that areas of low magnitude shear stress may provide a theoretical basis for the development of EV-based nanodrug delivery systems in vivo. Similarly, new approaches in clinical treatment are advancing, including the development of numerous novel mechanosensing carriers such as liposomes or microaggregates able to sense changes in shear force and respond by releasing biomolecules during mechanics-targeted drug delivery.…”

Section: The Role Of Reactive Oxygen Species In the Mechanoresponsive...mentioning

confidence: 99%

Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity

et al. 2022

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In recent years, our scientific interest in spaceflight has grown exponentially and resulted in a thriving area of research, with hundreds of astronauts spending months of their time in space. A recent shift toward pursuing territories farther afield, aiming at near-Earth asteroids, the Moon, and Mars combined with the anticipated availability of commercial flights to space in the near future, warrants continued understanding of the human physiological processes and response mechanisms when in this extreme environment. Acute skeletal loss, more severe than any bone loss seen on Earth, has significant implications for deep space exploration, and it remains elusive as to why there is such a magnitude of difference between bone loss on Earth and loss in microgravity. The removal of gravity eliminates a critical primary mechano-stimulus, and when combined with exposure to both galactic and solar cosmic radiation, healthy human tissue function can be negatively affected. An additional effect found in microgravity, and one with limited insight, involves changes in dynamic fluid flow. Fluids provide the most fundamental way to transport chemical and biochemical elements within our bodies and apply an essential mechano-stimulus to cells. Furthermore, the cell cytoplasm is not a simple liquid, and fluid transport phenomena together with viscoelastic deformation of the cytoskeleton play key roles in cell function. In microgravity, flow behavior changes drastically, and the impact on cells within the porous system of bone and the influence of an expanding level of adiposity are not well understood. This review explores the role of interstitial fluid motion and solute transport in porous bone under two different conditions: normogravity and microgravity.

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Uptake of oxidative stress-mediated extracellular vesicles by vascular endothelial cells under low magnitude shear stress

Cited by 25 publications

References 56 publications

Atheroprone shear stress stimulates noxious endothelial extracellular vesicle uptake by MCAM and PECAM-1 cell adhesion molecules

Atheroprone shear stress stimulates noxious endothelial extracellular vesicle uptake by MCAM and PECAM-1 cell adhesion molecules

Recent advances of natural and bioengineered extracellular vesicles and their application in vascular regeneration

Changes in interstitial fluid flow, mass transport and the bone cell response in microgravity and normogravity

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