Document Type
Article
Publication Date
5-16-2022
Abstract
Rationale: Extracellular vesicles (EVs) play a significant role in cell-cell communication. However, whether and how extracellular vesicles are involved in chronic intermittent hypoxia-induced endothelial dysfunction is unknown. Methods: Comparative transcriptomics analysis and miRNA screening were used to identify the possible pathways or target molecules mediating chronic intermittent hypoxia-induced endothelial function. Serum- or erythrocyte-derived EVs were isolated through ultracentrifugation plus filtration. After in vitro or in vivo treatment with EVs, aortic rings were treated with dihydroethidium staining for superoxidative anion measurement or mounted with wire myography to measure isometric forces. Immunoblotting and qPCR were used for evaluating the molecular mechanism mediating EV miR-144-induced endothelial function under intermittent hypoxia. Results: We revealed a previously undefined importance of circulating extracellular vesicles in regulating endothelial function via delivery of miR-144 to endothelial cells, reducing nuclear factor erythroid 2-related factor 2 expression. Additionally, we identified that erythrocytes were the primary cellular source of miR-144-enriched serum-derived extracellular vesicles and that erythrocyte-derived extracellular vesicles were largely responsible for chronic intermittent hypoxia-impaired endothelial function. Furthermore, silencing of miR-144 by anti-miR-144 confirmed its essential role in endothelial dysfunction elicited by erythrocyte-derived extracellular vesicles from chronic intermittent hypoxia-exposed C57BL/6 mice. Conclusion: The results expand the scope of blood-borne substances involved in vascular homeostasis and suggest that anti-miR-144-loaded extracellular vesicles may represent a promising therapeutic approach against obstructive sleep apnea or chronic intermittent hypoxia-associated endothelial dysfunction.
Recommended Citation
Zhang, Huina; Peng, Lu; Wang, Yifan; Zhao, Wen; Lau, Wayne Bond; Wang, Yajing; Li, Yu; Du, Yunhui; Li, Linyi; Huang, Yu; Nie, Shaoping; Qin, Yanwen; Ma, Xinliang; and Wei, Yongxiang, "Extracellular Vesicle-Derived miR-144 as a Novel Mechanism for Chronic Intermittent Hypoxia-induced Endothelial Dysfunction" (2022). Department of Emergency Medicine Faculty Papers. Paper 201.
https://jdc.jefferson.edu/emfp/201
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
35673562
Language
English
Comments
This article is the author's final published version in Ivyspring International Publisher, Volume 12, Issue 9, May 2022, Pages 4237 - 4249.
The published version is available at https://doi.org/10.7150/THNO.69035.
Copyright © The author(s)
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.