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 Tania Martins-Marques
A1 Teresa Ribeiro-Rodrigues
A1 Saskia C de Jager
A1 Monica Zuzarte
A1 Cátia Ferreira
A1 Pedro Cruz
A1 Liliana Reis
A1 Rui Baptista
A1 Lino Gonçalves
A1 Joost PG Sluijter
A1 Henrique Girao
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.