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01-06-2022 | Arterial Occlusive Disease

Exosomes Derived from Mesenchymal Stem Cells Ameliorate the Progression of Atherosclerosis in ApoE^−/− Mice via FENDRR

Authors: Nan Zhang, Yuxin Luo, Huaping Zhang, Feng Zhang, Xiang Gao, Jiawei Shao

Published in: Cardiovascular Toxicology | Issue 6/2022

Abstract

Exosomes (EXO) are extracellular vesicles with lipid bilayer membrane structure containing noncoding RNA, DNA, and other molecules which mediate biological functions. The importance of EXO derived from mesenchymal stem cells (MSCs) has been underlined in cardiovascular diseases. However, the functional role of long non-coding RNA (lncRNA) released by MSCs-EXO on atherosclerosis (AS) was unknown. We aimed to investigate the effects of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) released from MSC-derived EXO on AS. The accumulation of oxidized low-density lipoprotein (oxLDL) caused AS in mice and damage to human vascular endothelial cells (HUV-EC-C). MSC-EXO restored HUV-EC-C activity and alleviated arterial injury. LncRNA microarrays revealed that FENDRR was delivered to cells and tissues by MSC-EXO. FENDRR bound to microRNA (miR)-28 to regulate TEA domain transcription factor 1 (TEAD1) expression. Moreover, FENDRR knockdown exacerbated cell injury and arterial injury in mice. miR-28 inhibitor reversed the effects of FENDRR silencing and reduced atherosclerotic plaque formation. While loss of TEAD1 mitigated the effect of miR-28 inhibitor and accentuated HUV-EC-C injury in vitro and AS symptoms in vivo. Our results demonstrated that MSC-EXO secreted FENDRR to treat AS. FENDRR competed with TEAD1 to bind to miR-28, thereby reducing HUV-EC-C injury and atherosclerotic plaque formation.

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Title: Exosomes Derived from Mesenchymal Stem Cells Ameliorate the Progression of Atherosclerosis in ApoE−/− Mice via FENDRR
Authors: Nan Zhang
Yuxin Luo
Huaping Zhang
Feng Zhang
Xiang Gao
Jiawei Shao
Publication date: 01-06-2022
Publisher: Springer US
Keyword: Arterial Occlusive Disease
Published in: Cardiovascular Toxicology / Issue 6/2022
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-022-09736-8

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Exosomes Derived from Mesenchymal Stem Cells Ameliorate the Progression of Atherosclerosis in ApoE^−/− Mice via FENDRR

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