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Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro
Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes—nano‐sized, lipid vesicles released from cells—c...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742744/ https://www.ncbi.nlm.nih.gov/pubmed/28840975 http://dx.doi.org/10.1111/jcmm.13302 |
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author | Davidson, Sean M. Riquelme, Jaime A. Takov, Kaloyan Vicencio, Jose M. Boi‐Doku, Claire Khoo, Vanessa Doreth, Christian Radenkovic, Dina Lavandero, Sergio Yellon, Derek M. |
author_facet | Davidson, Sean M. Riquelme, Jaime A. Takov, Kaloyan Vicencio, Jose M. Boi‐Doku, Claire Khoo, Vanessa Doreth, Christian Radenkovic, Dina Lavandero, Sergio Yellon, Derek M. |
author_sort | Davidson, Sean M. |
collection | PubMed |
description | Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes—nano‐sized, lipid vesicles released from cells—can protect the hearts of non‐diabetic rats. We previously showed that exosomal HSP70 activates a cardioprotective signalling pathway in cardiomyocytes culminating in ERK1/2 and HSP27 phosphorylation. Here, we investigated whether the exosomal cardioprotective pathway remains intact in the setting of type II diabetes. Exosomes were isolated by differential centrifugation from non‐diabetic and type II diabetic patients, from non‐diabetic and Goto Kakizaki type II diabetic rats, and from normoglycaemic and hyperglycaemic endothelial cells. Exosome size and number were not significantly altered by diabetes. CD81 and HSP70 exosome markers were increased in diabetic rat exosomes. However, exosomes from diabetic rats no longer activated the ERK1/2 and HSP27 cardioprotective pathway and were no longer protective in a primary rat cardiomyocytes model of hypoxia and reoxygenation injury. Hyperglycaemic culture conditions were sufficient to impair protection by endothelial exosomes. Importantly, however, exosomes from non‐diabetic rats retained the ability to protect cardiomyocytes from diabetic rats. Exosomes from diabetic plasma have lost the ability to protect cardiomyocytes, but protection can be restored with exosomes from non‐diabetic plasma. These results support the concept that exosomes may be used to protect cardiomyocytes against ischaemia and reperfusion injury, even in the setting of type II diabetes. |
format | Online Article Text |
id | pubmed-5742744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57427442018-01-04 Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro Davidson, Sean M. Riquelme, Jaime A. Takov, Kaloyan Vicencio, Jose M. Boi‐Doku, Claire Khoo, Vanessa Doreth, Christian Radenkovic, Dina Lavandero, Sergio Yellon, Derek M. J Cell Mol Med Original Articles Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes—nano‐sized, lipid vesicles released from cells—can protect the hearts of non‐diabetic rats. We previously showed that exosomal HSP70 activates a cardioprotective signalling pathway in cardiomyocytes culminating in ERK1/2 and HSP27 phosphorylation. Here, we investigated whether the exosomal cardioprotective pathway remains intact in the setting of type II diabetes. Exosomes were isolated by differential centrifugation from non‐diabetic and type II diabetic patients, from non‐diabetic and Goto Kakizaki type II diabetic rats, and from normoglycaemic and hyperglycaemic endothelial cells. Exosome size and number were not significantly altered by diabetes. CD81 and HSP70 exosome markers were increased in diabetic rat exosomes. However, exosomes from diabetic rats no longer activated the ERK1/2 and HSP27 cardioprotective pathway and were no longer protective in a primary rat cardiomyocytes model of hypoxia and reoxygenation injury. Hyperglycaemic culture conditions were sufficient to impair protection by endothelial exosomes. Importantly, however, exosomes from non‐diabetic rats retained the ability to protect cardiomyocytes from diabetic rats. Exosomes from diabetic plasma have lost the ability to protect cardiomyocytes, but protection can be restored with exosomes from non‐diabetic plasma. These results support the concept that exosomes may be used to protect cardiomyocytes against ischaemia and reperfusion injury, even in the setting of type II diabetes. John Wiley and Sons Inc. 2017-08-25 2018-01 /pmc/articles/PMC5742744/ /pubmed/28840975 http://dx.doi.org/10.1111/jcmm.13302 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Davidson, Sean M. Riquelme, Jaime A. Takov, Kaloyan Vicencio, Jose M. Boi‐Doku, Claire Khoo, Vanessa Doreth, Christian Radenkovic, Dina Lavandero, Sergio Yellon, Derek M. Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro |
title | Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro
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title_full | Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro
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title_fullStr | Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro
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title_full_unstemmed | Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro
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title_short | Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non‐diabetic exosomes in vitro
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title_sort | cardioprotection mediated by exosomes is impaired in the setting of type ii diabetes but can be rescued by the use of non‐diabetic exosomes in vitro |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742744/ https://www.ncbi.nlm.nih.gov/pubmed/28840975 http://dx.doi.org/10.1111/jcmm.13302 |
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