TY - JOUR T1 - Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000821 VL - 3 IS - 12 SP - e202000821 AU - Tania Martins-Marques AU - Teresa Ribeiro-Rodrigues AU - Saskia C de Jager AU - Monica Zuzarte AU - Cátia Ferreira AU - Pedro Cruz AU - Liliana Reis AU - Rui Baptista AU - Lino Gonçalves AU - Joost PG Sluijter AU - Henrique Girao Y1 - 2020/12/01 UR - https://www.life-science-alliance.org/content/3/12/e202000821.abstract N2 - 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. ER -