Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning

Abstract Extracellular vesicles (EVs) such as exosomes are nano-sized vesicles that carry proteins and miRNAs and can transmit signals between cells. We hypothesized that exosomes from endothelial cells can transmit protective signals to cardiomyocytes. Co-culture of primary adult rat cardiomyocytes...

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Autores principales: Sean M. Davidson, Jaime A. Riquelme, Ying Zheng, Jose M. Vicencio, Sergio Lavandero, Derek M. Yellon
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/0e2d4a96a5c74a57b33fabee88b3c25c
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spelling oai:doaj.org-article:0e2d4a96a5c74a57b33fabee88b3c25c2021-12-02T11:40:46ZEndothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning10.1038/s41598-018-34357-z2045-2322https://doaj.org/article/0e2d4a96a5c74a57b33fabee88b3c25c2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34357-zhttps://doaj.org/toc/2045-2322Abstract Extracellular vesicles (EVs) such as exosomes are nano-sized vesicles that carry proteins and miRNAs and can transmit signals between cells. We hypothesized that exosomes from endothelial cells can transmit protective signals to cardiomyocytes. Co-culture of primary adult rat cardiomyocytes with normoxic HUVEC cells separated by a cell-impermeable membrane reduced the percentage of cardiomyocyte death following simulated ischaemia and reperfusion (sIR) from 80 ± 11% to 51 ± 4% (P < 0.05; N = 5). When EVs were removed from the HUVEC-conditioned medium it was no longer protective. Exosomes were purified from HUVEC-conditioned medium using differential centrifugation and characterized by nanoparticle tracking analysis, electron microscopy, and flow cytometry. Pre-incubation of cardiomyocytes with HUVEC exosomes reduced the percentage of cell death after sIR from 88 ± 4% to 55 ± 3% (P < 0.05; N = 3). This protection required ERK1/2 activity as it was prevented by inhibitors PD98059 and U0126. Ischaemic preconditioning caused about ~3-fold higher rate of exosome production from HUVEC and from isolated, perfused rat hearts. This increase resulted in significantly greater protection against sIR in cardiomyocytes. In conclusion, exosomes released from endothelial cells can confer resistance to sIR injury in cardiomyocytes via the activation of the ERK1/2 MAPK signalling pathway, and may contribute to IPC.Sean M. DavidsonJaime A. RiquelmeYing ZhengJose M. VicencioSergio LavanderoDerek M. YellonNature PortfolioarticleIschaemic Preconditioning (IPC)Human Umbilical Vein Endothelial Cells (HUVEC)Nanoparticle Tracking Analysis (NTA)Exosome ReleaseHUVEC CellsMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution DOAJ
collection DOAJ
language EN
topic Ischaemic Preconditioning (IPC)
Human Umbilical Vein Endothelial Cells (HUVEC)
Nanoparticle Tracking Analysis (NTA)
Exosome Release
HUVEC Cells
Medicine
R
Science
Q
spellingShingle Ischaemic Preconditioning (IPC)
Human Umbilical Vein Endothelial Cells (HUVEC)
Nanoparticle Tracking Analysis (NTA)
Exosome Release
HUVEC Cells
Medicine
R
Science
Q
Sean M. Davidson
Jaime A. Riquelme
Ying Zheng
Jose M. Vicencio
Sergio Lavandero
Derek M. Yellon
Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
description Abstract Extracellular vesicles (EVs) such as exosomes are nano-sized vesicles that carry proteins and miRNAs and can transmit signals between cells. We hypothesized that exosomes from endothelial cells can transmit protective signals to cardiomyocytes. Co-culture of primary adult rat cardiomyocytes with normoxic HUVEC cells separated by a cell-impermeable membrane reduced the percentage of cardiomyocyte death following simulated ischaemia and reperfusion (sIR) from 80 ± 11% to 51 ± 4% (P < 0.05; N = 5). When EVs were removed from the HUVEC-conditioned medium it was no longer protective. Exosomes were purified from HUVEC-conditioned medium using differential centrifugation and characterized by nanoparticle tracking analysis, electron microscopy, and flow cytometry. Pre-incubation of cardiomyocytes with HUVEC exosomes reduced the percentage of cell death after sIR from 88 ± 4% to 55 ± 3% (P < 0.05; N = 3). This protection required ERK1/2 activity as it was prevented by inhibitors PD98059 and U0126. Ischaemic preconditioning caused about ~3-fold higher rate of exosome production from HUVEC and from isolated, perfused rat hearts. This increase resulted in significantly greater protection against sIR in cardiomyocytes. In conclusion, exosomes released from endothelial cells can confer resistance to sIR injury in cardiomyocytes via the activation of the ERK1/2 MAPK signalling pathway, and may contribute to IPC.
format article
author Sean M. Davidson
Jaime A. Riquelme
Ying Zheng
Jose M. Vicencio
Sergio Lavandero
Derek M. Yellon
author_facet Sean M. Davidson
Jaime A. Riquelme
Ying Zheng
Jose M. Vicencio
Sergio Lavandero
Derek M. Yellon
author_sort Sean M. Davidson
title Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
title_short Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
title_full Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
title_fullStr Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
title_full_unstemmed Endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
title_sort endothelial cells release cardioprotective exosomes that may contribute to ischaemic preconditioning
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/0e2d4a96a5c74a57b33fabee88b3c25c
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AT yingzheng endothelialcellsreleasecardioprotectiveexosomesthatmaycontributetoischaemicpreconditioning
AT josemvicencio endothelialcellsreleasecardioprotectiveexosomesthatmaycontributetoischaemicpreconditioning
AT sergiolavandero endothelialcellsreleasecardioprotectiveexosomesthatmaycontributetoischaemicpreconditioning
AT derekmyellon endothelialcellsreleasecardioprotectiveexosomesthatmaycontributetoischaemicpreconditioning
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