RT Journal Article
SR Electronic
T1 Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000821
DO 10.26508/lsa.202000821
VO 3
IS 12
A1 Martins-Marques, Tania
A1 Ribeiro-Rodrigues, Teresa
A1 de Jager, Saskia C
A1 Zuzarte, Monica
A1 Ferreira, Cátia
A1 Cruz, Pedro
A1 Reis, Liliana
A1 Baptista, Rui
A1 Gonçalves, Lino
A1 Sluijter, Joost PG
A1 Girao, Henrique
YR 2020
UL https://www.life-science-alliance.org/content/3/12/e202000821.abstract
AB 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.