The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis

Abstract People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long‐term survivors. Extracellular vesicles (EVs) are involved in radiation‐induced endothelial dysfunction, but their role in the early stage of vascular inflammation aft...

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Main Authors: You Yeon Choi, Areumnuri Kim, Younghyun Lee, Yang Hee Lee, Mineon Park, Eunguk Shin, Sunhoo Park, BuHyun Youn, Ki Moon Seong
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:https://doi.org/10.1002/jev2.12325
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author You Yeon Choi
Areumnuri Kim
Younghyun Lee
Yang Hee Lee
Mineon Park
Eunguk Shin
Sunhoo Park
BuHyun Youn
Ki Moon Seong
author_facet You Yeon Choi
Areumnuri Kim
Younghyun Lee
Yang Hee Lee
Mineon Park
Eunguk Shin
Sunhoo Park
BuHyun Youn
Ki Moon Seong
author_sort You Yeon Choi
collection DOAJ
description Abstract People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long‐term survivors. Extracellular vesicles (EVs) are involved in radiation‐induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell‐derived EVs containing miRNAs initiate monocyte activation in radiation‐induced vascular inflammation. In vitro co‐culture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose‐dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell‐cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR‐126‐5p and miR‐212‐3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR‐126‐5p could be detected in the circulating endothelial EVs of radiation‐induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR‐126‐5p and miR‐212‐3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation‐induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.
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spelling doaj.art-162352d62ec3493eac0b6927c57444472023-05-23T05:54:28ZengWileyJournal of Extracellular Vesicles2001-30782023-05-01125n/an/a10.1002/jev2.12325The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosisYou Yeon Choi0Areumnuri Kim1Younghyun Lee2Yang Hee Lee3Mineon Park4Eunguk Shin5Sunhoo Park6BuHyun Youn7Ki Moon Seong8Laboratory of Biological Dosimetry National Radiation Emergency Medical Center, KIRAMS Seoul Republic of KoreaLaboratory of Radiation Exposure and Therapeutics National Radiation Emergency Medical Center KIRAMS Seoul Republic of KoreaLaboratory of Biological Dosimetry National Radiation Emergency Medical Center, KIRAMS Seoul Republic of KoreaLaboratory of Biological Dosimetry National Radiation Emergency Medical Center, KIRAMS Seoul Republic of KoreaLaboratory of Biological Dosimetry National Radiation Emergency Medical Center, KIRAMS Seoul Republic of KoreaDepartment of Biological Sciences Pusan National University Busan Republic of KoreaLaboratory of Biological Dosimetry National Radiation Emergency Medical Center, KIRAMS Seoul Republic of KoreaDepartment of Biological Sciences Pusan National University Busan Republic of KoreaLaboratory of Biological Dosimetry National Radiation Emergency Medical Center, KIRAMS Seoul Republic of KoreaAbstract People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long‐term survivors. Extracellular vesicles (EVs) are involved in radiation‐induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell‐derived EVs containing miRNAs initiate monocyte activation in radiation‐induced vascular inflammation. In vitro co‐culture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose‐dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell‐cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR‐126‐5p and miR‐212‐3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR‐126‐5p could be detected in the circulating endothelial EVs of radiation‐induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR‐126‐5p and miR‐212‐3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation‐induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.https://doi.org/10.1002/jev2.12325endotheliumextracellular vesiclemiRNAsmonocytesradiation exposure
spellingShingle You Yeon Choi
Areumnuri Kim
Younghyun Lee
Yang Hee Lee
Mineon Park
Eunguk Shin
Sunhoo Park
BuHyun Youn
Ki Moon Seong
The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis
Journal of Extracellular Vesicles
endothelium
extracellular vesicle
miRNAs
monocytes
radiation exposure
title The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis
title_full The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis
title_fullStr The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis
title_full_unstemmed The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis
title_short The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis
title_sort mir 126 5p and mir 212 3p in the extracellular vesicles activate monocytes in the early stage of radiation induced vascular inflammation implicated in atherosclerosis
topic endothelium
extracellular vesicle
miRNAs
monocytes
radiation exposure
url https://doi.org/10.1002/jev2.12325
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