Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
Martins-Marques, Tania; Ribeiro-Rodrigues, Teresa; de Jager, Saskia C.; Zuzarte, Monica; Ferreira, Cátia; Cruz, Pedro; Reis, Liliana; Baptista, Rui; Gonçalves, Lino; Sluijter, Joost P.G.; Girao, Henrique
(2020) Life Science Alliance, volume 3, issue 12, pp. 1 - 16
(Article)
Abstract
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
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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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Keywords: Biochemistry, Genetics and Molecular Biology (miscellaneous), Health, Toxicology and Mutagenesis, Plant Science, Ecology, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2575-1077
Publisher: Rockefeller University Press
Note: Funding Information: This work was supported by the European Regional Development Fund through the Operational Program for Competitiveness Factors (COMPETE) (under the projects PAC “NETDIAMOND” POCI-01-0145-FEDER-016385; HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323; POCI-01-0145-FEDER-007440, CENTRO-01-0145-FEDER-032179, CENTRO-01-0145-FEDER-032414, POCI-01-0145-FEDER-022122, FCTUID/NEU/04539/2013, UID/NEU/04539/2019, UIDB/04539/2020, and UIDP/ 04539/2020). This work was supported by the Project EVICARE (No. 725229) of the European Research Council to JPG Sluijter. T Martins-Marques was supported by PD/BD/106043/2015 and T Ribeiro-Rodrigues by PD/BD/52294/2013 from Fundação para a Ciência e a Tecnologia (FCT). Funding Information: This work was supported by the European Regional Development Fund through the Operational Program for Competitiveness Factors (COMPETE) (under the projects PAC ?NETDIAMOND? POCI-01-0145-FEDER-016385; HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323; POCI-01-0145-FEDER-007440, CENTRO-01-0145-FEDER-032179, CENTRO-01-0145-FEDER-032414, POCI-01-0145-FEDER-022122, FCTUID/NEU/04539/2013, UID/NEU/04539/2019, UIDB/04539/2020, and UIDP/ 04539/2020). This work was supported by the Project EVICARE (No. 725229) of the European Research Council to JPG Sluijter. T Martins-Marques was supported by PD/BD/106043/2015 and T Ribeiro-Rodrigues by PD/BD/52294/2013 from Funda??o para a Ci?ncia e a Tecnologia (FCT). Publisher Copyright: © 2020 Martins-Marques et al.
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