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Endothelial activation impairs the function of small extracellular vesicles

Small extracellular vesicles are nanosized vesicles (30–200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-re...

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Autores principales: Herrera-Zelada, Nicolas, Zúñiga-Cuevas, Úrsula, Ramírez-Reyes, Andrés, Norambuena-Soto, Ignacio, Venegas-Zamora, Leslye, Troncoso, Mayarling F., Hernández, Alejandra, Sánchez, Gina, Pedrozo, Zully, Lavandero, Sergio, Riquelme, Jaime A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083389/
https://www.ncbi.nlm.nih.gov/pubmed/37050899
http://dx.doi.org/10.3389/fphar.2023.1143888
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author Herrera-Zelada, Nicolas
Zúñiga-Cuevas, Úrsula
Ramírez-Reyes, Andrés
Norambuena-Soto, Ignacio
Venegas-Zamora, Leslye
Troncoso, Mayarling F.
Hernández, Alejandra
Sánchez, Gina
Pedrozo, Zully
Lavandero, Sergio
Riquelme, Jaime A.
author_facet Herrera-Zelada, Nicolas
Zúñiga-Cuevas, Úrsula
Ramírez-Reyes, Andrés
Norambuena-Soto, Ignacio
Venegas-Zamora, Leslye
Troncoso, Mayarling F.
Hernández, Alejandra
Sánchez, Gina
Pedrozo, Zully
Lavandero, Sergio
Riquelme, Jaime A.
author_sort Herrera-Zelada, Nicolas
collection PubMed
description Small extracellular vesicles are nanosized vesicles (30–200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were isolated from endothelial cells treated with or without TNF-α 10 ng/mL using size exclusion chromatography. The size and concentration of SEVs was measured by Nanoparticle Tracking Analysis. The expression of the surface marker CD81 was determined by immunoassay, whereas their morphology was assessed by electron microscopy. The function of endothelial SEVs was assessed by evaluating their cardioprotective effect in an ex vivo model of global I/R using isolated hearts from adult C57BL/6 mice. Treatment of HUVECs with TNF-α induced the expression of VCAM-1 and ICAM-1, whereas eNOS levels were decreased. TNF-α did not affect the production, size, morphology, or expression of CD81. SEVs significantly reduced the infarct size as compared with untreated mice hearts, but SEVs isolated from TNF-α treated cells were unable to achieve this effect. Therefore, a pro-inflammatory state induced by TNF-α does not alter the production of endothelial SEVs but impairs their function in the setting of I/R injury.
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spelling pubmed-100833892023-04-11 Endothelial activation impairs the function of small extracellular vesicles Herrera-Zelada, Nicolas Zúñiga-Cuevas, Úrsula Ramírez-Reyes, Andrés Norambuena-Soto, Ignacio Venegas-Zamora, Leslye Troncoso, Mayarling F. Hernández, Alejandra Sánchez, Gina Pedrozo, Zully Lavandero, Sergio Riquelme, Jaime A. Front Pharmacol Pharmacology Small extracellular vesicles are nanosized vesicles (30–200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were isolated from endothelial cells treated with or without TNF-α 10 ng/mL using size exclusion chromatography. The size and concentration of SEVs was measured by Nanoparticle Tracking Analysis. The expression of the surface marker CD81 was determined by immunoassay, whereas their morphology was assessed by electron microscopy. The function of endothelial SEVs was assessed by evaluating their cardioprotective effect in an ex vivo model of global I/R using isolated hearts from adult C57BL/6 mice. Treatment of HUVECs with TNF-α induced the expression of VCAM-1 and ICAM-1, whereas eNOS levels were decreased. TNF-α did not affect the production, size, morphology, or expression of CD81. SEVs significantly reduced the infarct size as compared with untreated mice hearts, but SEVs isolated from TNF-α treated cells were unable to achieve this effect. Therefore, a pro-inflammatory state induced by TNF-α does not alter the production of endothelial SEVs but impairs their function in the setting of I/R injury. Frontiers Media S.A. 2023-03-27 /pmc/articles/PMC10083389/ /pubmed/37050899 http://dx.doi.org/10.3389/fphar.2023.1143888 Text en Copyright © 2023 Herrera-Zelada, Zúñiga-Cuevas, Ramírez-Reyes, Norambuena-Soto, Venegas-Zamora, Troncoso, Hernández, Sánchez, Pedrozo, Lavandero and Riquelme. 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 Pharmacology
Herrera-Zelada, Nicolas
Zúñiga-Cuevas, Úrsula
Ramírez-Reyes, Andrés
Norambuena-Soto, Ignacio
Venegas-Zamora, Leslye
Troncoso, Mayarling F.
Hernández, Alejandra
Sánchez, Gina
Pedrozo, Zully
Lavandero, Sergio
Riquelme, Jaime A.
Endothelial activation impairs the function of small extracellular vesicles
title Endothelial activation impairs the function of small extracellular vesicles
title_full Endothelial activation impairs the function of small extracellular vesicles
title_fullStr Endothelial activation impairs the function of small extracellular vesicles
title_full_unstemmed Endothelial activation impairs the function of small extracellular vesicles
title_short Endothelial activation impairs the function of small extracellular vesicles
title_sort endothelial activation impairs the function of small extracellular vesicles
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083389/
https://www.ncbi.nlm.nih.gov/pubmed/37050899
http://dx.doi.org/10.3389/fphar.2023.1143888
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