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
Author
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Davidson, Sean M.
Author
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Riquelme, Jaime A.
Author
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Takov, Kaloyan
Author
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Vicencio, José M.
Author
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Boi-Doku, Claire
Author
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Khoo, Vanessa
Author
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Doreth, Christian
Author
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Radenkovic, Dina
Author
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Lavandero González, Sergio
Author
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Yellon, Derek M.
Admission date
dc.date.accessioned
2019-03-18T11:59:43Z
Available date
dc.date.available
2019-03-18T11:59:43Z
Publication date
dc.date.issued
2018
Cita de ítem
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J. Cell. Mol. Med. Vol 22, No 1, 2018 pp. 141-151
Identifier
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15821838
Identifier
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10.1111/jcmm.13302
Identifier
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https://repositorio.uchile.cl/handle/2250/167244
Abstract
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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.