Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , |
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. |
id |
RCAP_4e3acf09d9fdfa0505683dedee038117 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/101258 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 |
dc.date.none.fl_str_mv |
2020 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/101258 http://hdl.handle.net/10316/101258 https://doi.org/10.26508/lsa.202000821 |
url |
http://hdl.handle.net/10316/101258 https://doi.org/10.26508/lsa.202000821 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2575-1077 33097557 2575-1077 33097557 2575-1077 2575-1077 33097557 33097557 2575-1077 33097557 2575-1077 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134079683133440 |