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Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction
Mounting evidence suggests that extracellular vesicles (EVs) are effective communicators in biological signalling in cardiac physiology and pathology. However, the role of EVs in cardiac injury, particularly in ischemic myocardial scenarios, has not been fully elucidated. Here, we report that acute...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028097/ https://www.ncbi.nlm.nih.gov/pubmed/35452193 http://dx.doi.org/10.1002/ctm2.779 |
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author | Sun, Ping Wang, Chao Mang, Ge Xu, Xiangli Fu, Shuai Chen, Jianfeng Wang, Xiaoqi Wang, Weiwei Li, Hairu Zhao, Peng Li, Yifei Chen, Qi Wang, Naixin Tong, Zhonghua Fu, Xin Lang, Ying Duan, Shasha Liu, Dongmei Zhang, Maomao Tian, Jiawei |
author_facet | Sun, Ping Wang, Chao Mang, Ge Xu, Xiangli Fu, Shuai Chen, Jianfeng Wang, Xiaoqi Wang, Weiwei Li, Hairu Zhao, Peng Li, Yifei Chen, Qi Wang, Naixin Tong, Zhonghua Fu, Xin Lang, Ying Duan, Shasha Liu, Dongmei Zhang, Maomao Tian, Jiawei |
author_sort | Sun, Ping |
collection | PubMed |
description | Mounting evidence suggests that extracellular vesicles (EVs) are effective communicators in biological signalling in cardiac physiology and pathology. However, the role of EVs in cardiac injury, particularly in ischemic myocardial scenarios, has not been fully elucidated. Here, we report that acute myocardial infarction (AMI)‐induced EVs can impair cardiomyocyte survival and exacerbate cardiac injury. EV‐encapsulated miR‐503, which is enriched during the early phase of AMI, is a critical molecule that mediates myocardial injury. Functional studies revealed that miR‐503 promoted cardiomyocyte death by directly binding to peroxisome proliferator‐activated receptor gamma coactivator‐1β (PGC‐1β) and a mitochondrial deacetylase, sirtuin 3 (SIRT3), thereby triggering mitochondrial metabolic dysfunction and cardiomyocyte death. Mechanistically, we identified endothelial cells as the primary source of miR‐503 in EVs after AMI. Hypoxia induced rapid H3K4 methylation of the promoter of the methyltransferase‐like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6‐methyladenosine (m(6)A)‐dependent miR‐503 biogenesis in endothelial cells. In summary, this study highlights a novel endogenous mechanism wherein EVs aggravate myocardial injury during the onset of AMI via endothelial cell‐secreted miR‐503 shuttling. |
format | Online Article Text |
id | pubmed-9028097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90280972022-05-24 Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction Sun, Ping Wang, Chao Mang, Ge Xu, Xiangli Fu, Shuai Chen, Jianfeng Wang, Xiaoqi Wang, Weiwei Li, Hairu Zhao, Peng Li, Yifei Chen, Qi Wang, Naixin Tong, Zhonghua Fu, Xin Lang, Ying Duan, Shasha Liu, Dongmei Zhang, Maomao Tian, Jiawei Clin Transl Med Research Articles Mounting evidence suggests that extracellular vesicles (EVs) are effective communicators in biological signalling in cardiac physiology and pathology. However, the role of EVs in cardiac injury, particularly in ischemic myocardial scenarios, has not been fully elucidated. Here, we report that acute myocardial infarction (AMI)‐induced EVs can impair cardiomyocyte survival and exacerbate cardiac injury. EV‐encapsulated miR‐503, which is enriched during the early phase of AMI, is a critical molecule that mediates myocardial injury. Functional studies revealed that miR‐503 promoted cardiomyocyte death by directly binding to peroxisome proliferator‐activated receptor gamma coactivator‐1β (PGC‐1β) and a mitochondrial deacetylase, sirtuin 3 (SIRT3), thereby triggering mitochondrial metabolic dysfunction and cardiomyocyte death. Mechanistically, we identified endothelial cells as the primary source of miR‐503 in EVs after AMI. Hypoxia induced rapid H3K4 methylation of the promoter of the methyltransferase‐like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6‐methyladenosine (m(6)A)‐dependent miR‐503 biogenesis in endothelial cells. In summary, this study highlights a novel endogenous mechanism wherein EVs aggravate myocardial injury during the onset of AMI via endothelial cell‐secreted miR‐503 shuttling. John Wiley and Sons Inc. 2022-04-22 /pmc/articles/PMC9028097/ /pubmed/35452193 http://dx.doi.org/10.1002/ctm2.779 Text en © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Sun, Ping Wang, Chao Mang, Ge Xu, Xiangli Fu, Shuai Chen, Jianfeng Wang, Xiaoqi Wang, Weiwei Li, Hairu Zhao, Peng Li, Yifei Chen, Qi Wang, Naixin Tong, Zhonghua Fu, Xin Lang, Ying Duan, Shasha Liu, Dongmei Zhang, Maomao Tian, Jiawei Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction |
title | Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction |
title_full | Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction |
title_fullStr | Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction |
title_full_unstemmed | Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction |
title_short | Extracellular vesicle‐packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction |
title_sort | extracellular vesicle‐packaged mitochondrial disturbing mirna exacerbates cardiac injury during acute myocardial infarction |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028097/ https://www.ncbi.nlm.nih.gov/pubmed/35452193 http://dx.doi.org/10.1002/ctm2.779 |
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