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Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis
As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510661/ https://www.ncbi.nlm.nih.gov/pubmed/36172581 http://dx.doi.org/10.3389/fcvm.2022.1003282 |
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author | Man, Wanrong Song, Xinglong Xiong, Zhenyu Gu, Jing Lin, Jie Gu, Xiaoming Yu, Duan Li, Congye Jiang, Mengyuan Zhang, Xuebin Yang, Zhi Cao, Yang Zhang, Yan Shu, Xiaofei Wu, Dexi Wang, Haichang Ji, Gang Sun, Dongdong |
author_facet | Man, Wanrong Song, Xinglong Xiong, Zhenyu Gu, Jing Lin, Jie Gu, Xiaoming Yu, Duan Li, Congye Jiang, Mengyuan Zhang, Xuebin Yang, Zhi Cao, Yang Zhang, Yan Shu, Xiaofei Wu, Dexi Wang, Haichang Ji, Gang Sun, Dongdong |
author_sort | Man, Wanrong |
collection | PubMed |
description | As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury. In vitro experiments were conducted to evaluate the effects of Adipsin on cardiomyocyte function in the face of hypoxic challenge and the mechanisms involved. Our results showed that Adipsin dramatically altered expression of proteins associated with iron metabolism and ferroptosis. In vivo results demonstrated that Adipsin upregulated levels of Ferritin Heavy Chain (FTH) while downregulating that of Transferrin Receptor (TFRC) in peri-infarct regions 1 month following MI. Adipsin also relieved post-MI-associated lipid oxidative stress as evidenced by decreased expression of COX2 and increased GPX4 level. Co-immunoprecipitation and immunofluorescence imaging prove a direct interaction between Adipsin and IRP2. As expected, cardioprotection provided by Adipsin depends on the key molecule of IRP2. These findings revealed that Adipsin could be efficiently delivered to the heart by exosomes derived from pericardial adipose tissues. In addition, Adipsin interacted with IRP2 to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. Therefore, Adipsin-overexpressed exosomes derived from pericardial adipose tissues may be a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury. |
format | Online Article Text |
id | pubmed-9510661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95106612022-09-27 Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis Man, Wanrong Song, Xinglong Xiong, Zhenyu Gu, Jing Lin, Jie Gu, Xiaoming Yu, Duan Li, Congye Jiang, Mengyuan Zhang, Xuebin Yang, Zhi Cao, Yang Zhang, Yan Shu, Xiaofei Wu, Dexi Wang, Haichang Ji, Gang Sun, Dongdong Front Cardiovasc Med Cardiovascular Medicine As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury. In vitro experiments were conducted to evaluate the effects of Adipsin on cardiomyocyte function in the face of hypoxic challenge and the mechanisms involved. Our results showed that Adipsin dramatically altered expression of proteins associated with iron metabolism and ferroptosis. In vivo results demonstrated that Adipsin upregulated levels of Ferritin Heavy Chain (FTH) while downregulating that of Transferrin Receptor (TFRC) in peri-infarct regions 1 month following MI. Adipsin also relieved post-MI-associated lipid oxidative stress as evidenced by decreased expression of COX2 and increased GPX4 level. Co-immunoprecipitation and immunofluorescence imaging prove a direct interaction between Adipsin and IRP2. As expected, cardioprotection provided by Adipsin depends on the key molecule of IRP2. These findings revealed that Adipsin could be efficiently delivered to the heart by exosomes derived from pericardial adipose tissues. In addition, Adipsin interacted with IRP2 to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. Therefore, Adipsin-overexpressed exosomes derived from pericardial adipose tissues may be a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury. Frontiers Media S.A. 2022-09-12 /pmc/articles/PMC9510661/ /pubmed/36172581 http://dx.doi.org/10.3389/fcvm.2022.1003282 Text en Copyright © 2022 Man, Song, Xiong, Gu, Lin, Gu, Yu, Li, Jiang, Zhang, Yang, Cao, Zhang, Shu, Wu, Wang, Ji and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Man, Wanrong Song, Xinglong Xiong, Zhenyu Gu, Jing Lin, Jie Gu, Xiaoming Yu, Duan Li, Congye Jiang, Mengyuan Zhang, Xuebin Yang, Zhi Cao, Yang Zhang, Yan Shu, Xiaofei Wu, Dexi Wang, Haichang Ji, Gang Sun, Dongdong Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis |
title | Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis |
title_full | Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis |
title_fullStr | Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis |
title_full_unstemmed | Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis |
title_short | Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis |
title_sort | exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by adipsin-regulated iron homeostasis |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510661/ https://www.ncbi.nlm.nih.gov/pubmed/36172581 http://dx.doi.org/10.3389/fcvm.2022.1003282 |
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