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

• DOI: 10.1016/j.bioactmat.2021.10.038
• Publication Date: 2021-11-06T11:43:01Z
• Authors: Xian Qin; Kun Zhang; Juhui Qiu; Nan Wang; Kai Qu; Yuliang Cui; Junli Huang; Li Luo; Yuan Zhong; Tian Tian; Wei Wu; Yi Wang; Guixue Wang
• Keywords: 0301 basic medicine; Blood flow shear stress; QH301-705.5; Article; 3. Good health; 03 medical and health sciences; Oxidative stress; TA401-492; Nanoparticles; Extracellular vesicles (EVs); Endothelial cell uptake; Biology (General); Materials of engineering and construction. Mechanics of materials

Extracellular vesicles (EVs) are increasingly used as delivery vehicles for drugs and bioactive molecules, which usually require intravascular administration. The endothelial cells covering the inner surface of blood vessels are susceptible to the shear stress of blood flow. Few studies demonstrate the interplay of red blood cell-derived EVs (RBCEVs) and endothelial cells. Thus, the phagocytosis of EVs by vascular endothelial cells during blood flow needs to be elucidated. In this study, red blood cell-derived extracellular vesicles (RBCEVs) were constructed to investigate endothelial cell phagocytosis in vitro and animal models. Results showed that low magnitude shear stress including low shear stress (LSS) and oscillatory shear stress (OSS) could promote the uptake of RBCEVs by endothelial cells in vitro. In addition, in zebrafish and mouse models, RBCEVs tend to be internalized by endothelial cells under LSS or OSS. Moreover, RBCEVs are easily engulfed by endothelial cells in atherosclerotic plaques exposed to LSS or OSS. In terms of mechanism, oxidative stress induced by LSS is part of the reason for the increased uptake of endothelial cells. Overall, this study shows that vascular endothelial cells can easily engulf EVs in areas of low magnitude shear stress, which will provide a theoretical basis for the development and utilization of EVs-based nano-drug delivery systems in vivo.