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Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice

The release of extracellular vesicles (EVs) is increased under cellular stress and cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs eventually reach the systemic circulation and whether their number in the bloodstream reflects cardiac injury, remains unknown. Wild ty...

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Autores principales: Hegyesi, Hargita, Pallinger, Éva, Mecsei, Szabina, Hornyák, Balázs, Kovácsházi, Csenger, Brenner, Gábor B., Giricz, Zoltán, Pálóczi, Krisztina, Kittel, Ágnes, Tóvári, József, Turiak, Lilla, Khamari, Delaram, Ferdinandy, Péter, Buzás, Edit I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776681/
https://www.ncbi.nlm.nih.gov/pubmed/35059851
http://dx.doi.org/10.1007/s00018-021-04125-w
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author Hegyesi, Hargita
Pallinger, Éva
Mecsei, Szabina
Hornyák, Balázs
Kovácsházi, Csenger
Brenner, Gábor B.
Giricz, Zoltán
Pálóczi, Krisztina
Kittel, Ágnes
Tóvári, József
Turiak, Lilla
Khamari, Delaram
Ferdinandy, Péter
Buzás, Edit I.
author_facet Hegyesi, Hargita
Pallinger, Éva
Mecsei, Szabina
Hornyák, Balázs
Kovácsházi, Csenger
Brenner, Gábor B.
Giricz, Zoltán
Pálóczi, Krisztina
Kittel, Ágnes
Tóvári, József
Turiak, Lilla
Khamari, Delaram
Ferdinandy, Péter
Buzás, Edit I.
author_sort Hegyesi, Hargita
collection PubMed
description The release of extracellular vesicles (EVs) is increased under cellular stress and cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs eventually reach the systemic circulation and whether their number in the bloodstream reflects cardiac injury, remains unknown. Wild type C57B/6 and conditional transgenic mice expressing green fluorescent protein (GFP) by cardiomyocytes were studied in lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome (SIRS). EVs were separated both from platelet-free plasma and from the conditioned medium of isolated cardiomyocytes of the left ventricular wall. Size distribution and concentration of the released particles were determined by Nanoparticle Tracking Analysis. The presence of GFP + cardiomyocyte-derived circulating EVs was monitored by flow cytometry and cardiac function was assessed by echocardiography. In LPS-treated mice, systemic inflammation and the consequent cardiomyopathy were verified by elevated plasma levels of TNFα, GDF-15, and cardiac troponin I, and by a decrease in the ejection fraction. Furthermore, we demonstrated elevated levels of circulating small- and medium-sized EVs in the LPS-injected mice. Importantly, we detected GFP(+) cardiomyocyte-derived EVs in the circulation of control mice, and the number of these circulating GFP(+) vesicles increased significantly upon intraperitoneal LPS administration (P = 0.029). The cardiomyocyte-derived GFP(+) EVs were also positive for intravesicular troponin I (cTnI) and muscle-associated glycogen phosphorylase (PYGM). This is the first direct demonstration that cardiomyocyte-derived EVs are present in the circulation and that the increased number of cardiac-derived EVs in the blood reflects cardiac injury in LPS-induced systemic inflammation (SIRS). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-04125-w.
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spelling pubmed-87766812022-02-02 Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice Hegyesi, Hargita Pallinger, Éva Mecsei, Szabina Hornyák, Balázs Kovácsházi, Csenger Brenner, Gábor B. Giricz, Zoltán Pálóczi, Krisztina Kittel, Ágnes Tóvári, József Turiak, Lilla Khamari, Delaram Ferdinandy, Péter Buzás, Edit I. Cell Mol Life Sci Original Article The release of extracellular vesicles (EVs) is increased under cellular stress and cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs eventually reach the systemic circulation and whether their number in the bloodstream reflects cardiac injury, remains unknown. Wild type C57B/6 and conditional transgenic mice expressing green fluorescent protein (GFP) by cardiomyocytes were studied in lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome (SIRS). EVs were separated both from platelet-free plasma and from the conditioned medium of isolated cardiomyocytes of the left ventricular wall. Size distribution and concentration of the released particles were determined by Nanoparticle Tracking Analysis. The presence of GFP + cardiomyocyte-derived circulating EVs was monitored by flow cytometry and cardiac function was assessed by echocardiography. In LPS-treated mice, systemic inflammation and the consequent cardiomyopathy were verified by elevated plasma levels of TNFα, GDF-15, and cardiac troponin I, and by a decrease in the ejection fraction. Furthermore, we demonstrated elevated levels of circulating small- and medium-sized EVs in the LPS-injected mice. Importantly, we detected GFP(+) cardiomyocyte-derived EVs in the circulation of control mice, and the number of these circulating GFP(+) vesicles increased significantly upon intraperitoneal LPS administration (P = 0.029). The cardiomyocyte-derived GFP(+) EVs were also positive for intravesicular troponin I (cTnI) and muscle-associated glycogen phosphorylase (PYGM). This is the first direct demonstration that cardiomyocyte-derived EVs are present in the circulation and that the increased number of cardiac-derived EVs in the blood reflects cardiac injury in LPS-induced systemic inflammation (SIRS). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-04125-w. Springer International Publishing 2022-01-20 2022 /pmc/articles/PMC8776681/ /pubmed/35059851 http://dx.doi.org/10.1007/s00018-021-04125-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Hegyesi, Hargita
Pallinger, Éva
Mecsei, Szabina
Hornyák, Balázs
Kovácsházi, Csenger
Brenner, Gábor B.
Giricz, Zoltán
Pálóczi, Krisztina
Kittel, Ágnes
Tóvári, József
Turiak, Lilla
Khamari, Delaram
Ferdinandy, Péter
Buzás, Edit I.
Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
title Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
title_full Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
title_fullStr Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
title_full_unstemmed Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
title_short Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
title_sort circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776681/
https://www.ncbi.nlm.nih.gov/pubmed/35059851
http://dx.doi.org/10.1007/s00018-021-04125-w
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