Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes

Detalhes bibliográficos
Autor(a) principal: Martins-Marques, Tânia
Data de Publicação: 2020
Outros Autores: Rodrigues, Teresa Ribeiro, de Jager, Saskia C, Zuzarte, Mónica, Ferreira, Cátia, Cruz, Pedro, Reis, Liliana, Baptista, Rui, Gonçalves, Lino, Sluijter, Joost Pg, Girão, Henrique
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/101258
https://doi.org/10.26508/lsa.202000821
Resumo: Ischemic heart disease has been associated with an impairment on intercellular communication mediated by both gap junctions and extracellular vesicles. We have previously shown that connexin 43 (Cx43), the main ventricular gap junction protein, assembles into channels at the extracellular vesicle surface, mediating the release of vesicle content into target cells. Here, using a comprehensive strategy that included cell-based approaches, animal models and human patients, we demonstrate that myocardial ischemia impairs the secretion of Cx43 into circulating, intracardiac and cardiomyocyte-derived vesicles. In addition, we show that ubiquitin signals Cx43 release in basal conditions but appears to be dispensable during ischemia, suggesting an interplay between ischemia-induced Cx43 degradation and secretion. Overall, this study constitutes a step forward for the characterization of the signals and molecular players underlying vesicle protein sorting, with strong implications on long-range intercellular communication, paving the way towards the development of innovative diagnostic and therapeutic strategies for cardiovascular disorders.
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spelling Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytesIschemic heart disease has been associated with an impairment on intercellular communication mediated by both gap junctions and extracellular vesicles. We have previously shown that connexin 43 (Cx43), the main ventricular gap junction protein, assembles into channels at the extracellular vesicle surface, mediating the release of vesicle content into target cells. Here, using a comprehensive strategy that included cell-based approaches, animal models and human patients, we demonstrate that myocardial ischemia impairs the secretion of Cx43 into circulating, intracardiac and cardiomyocyte-derived vesicles. In addition, we show that ubiquitin signals Cx43 release in basal conditions but appears to be dispensable during ischemia, suggesting an interplay between ischemia-induced Cx43 degradation and secretion. Overall, this study constitutes a step forward for the characterization of the signals and molecular players underlying vesicle protein sorting, with strong implications on long-range intercellular communication, paving the way towards the development of innovative diagnostic and therapeutic strategies for cardiovascular disorders.2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/101258http://hdl.handle.net/10316/101258https://doi.org/10.26508/lsa.202000821eng2575-1077330975572575-1077330975572575-10772575-107733097557330975572575-1077330975572575-1077Martins-Marques, TâniaRodrigues, Teresa Ribeirode Jager, Saskia CZuzarte, MónicaFerreira, CátiaCruz, PedroReis, LilianaBaptista, RuiGonçalves, LinoSluijter, Joost PgGirão, Henriqueinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-08-18T20:43:47Zoai:estudogeral.uc.pt:10316/101258Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:18:29.482173Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
title Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
spellingShingle Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
Martins-Marques, Tânia
title_short Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
title_full Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
title_fullStr Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
title_full_unstemmed Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
title_sort Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
author Martins-Marques, Tânia
author_facet Martins-Marques, Tânia
Rodrigues, Teresa Ribeiro
de Jager, Saskia C
Zuzarte, Mónica
Ferreira, Cátia
Cruz, Pedro
Reis, Liliana
Baptista, Rui
Gonçalves, Lino
Sluijter, Joost Pg
Girão, Henrique
author_role author
author2 Rodrigues, Teresa Ribeiro
de Jager, Saskia C
Zuzarte, Mónica
Ferreira, Cátia
Cruz, Pedro
Reis, Liliana
Baptista, Rui
Gonçalves, Lino
Sluijter, Joost Pg
Girão, Henrique
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Martins-Marques, Tânia
Rodrigues, Teresa Ribeiro
de Jager, Saskia C
Zuzarte, Mónica
Ferreira, Cátia
Cruz, Pedro
Reis, Liliana
Baptista, Rui
Gonçalves, Lino
Sluijter, Joost Pg
Girão, Henrique
description Ischemic heart disease has been associated with an impairment on intercellular communication mediated by both gap junctions and extracellular vesicles. We have previously shown that connexin 43 (Cx43), the main ventricular gap junction protein, assembles into channels at the extracellular vesicle surface, mediating the release of vesicle content into target cells. Here, using a comprehensive strategy that included cell-based approaches, animal models and human patients, we demonstrate that myocardial ischemia impairs the secretion of Cx43 into circulating, intracardiac and cardiomyocyte-derived vesicles. In addition, we show that ubiquitin signals Cx43 release in basal conditions but appears to be dispensable during ischemia, suggesting an interplay between ischemia-induced Cx43 degradation and secretion. Overall, this study constitutes a step forward for the characterization of the signals and molecular players underlying vesicle protein sorting, with strong implications on long-range intercellular communication, paving the way towards the development of innovative diagnostic and therapeutic strategies for cardiovascular disorders.
publishDate 2020
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https://doi.org/10.26508/lsa.202000821
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https://doi.org/10.26508/lsa.202000821
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