Extracellular Vesicles Secreted by Hypoxic AC10 Cardiomyocytes Modulate Fibroblast Cell Motility

[EN] Extracellular vesicles (EVs) are small membrane vesicles secreted by most cell types with important roles in cell-to-cell communication. To assess their relevance in the context of heart ischemia, EVs isolated from the AC10 ventricular cardiomyocyte cell line (CM-EVs), exposed to normoxia (Nx) or hypoxia (Hx), were incubated with fibroblasts (Fb) and endothelial cells (EC). CM-EVs were studied using electron microscopy, nanoparticle tracking analysis (NTA), western blotting and proteomic analysis. Results showed that EVs had a strong preference to be internalized by EC over fibroblasts, suggesting an active exosome-based communication mechanism between CM and EC in the heart. In Matrigel tube-formation assays, Hx CM-EVs were inferior to Nx CM-EVs in angiogenesis. By contrast, in a wound-healing assay, wound closure was faster in fibroblasts treated with Hx CM-EVs than with Nx CM-EVs, supporting a pro-fibrotic effect of Hx CM-EVs. Overall, these observations were consistent with the different protein cargoes detected by proteomic analysis under Nx and Hx conditions and the biological pathways identified. The paracrine crosstalk between CM-EVs, Fb, and EC in different physiological conditions could account for the contribution of CM-EVs to cardiac remodeling after an ischemic insult. This work was supported by grants PI16/0107 and RETICS Program (RD16/0011/0004) from Instituto de Salud Carlos III cofunded by the European Regional Development Fund ERDF una manera de hacer Europa. The proteomic studies were carried out in the University of Valencia Proteomics Unit, a member of the ISCIII ProteoRed Proteomics Platform. The bioinformatics analysis was performed in the Bioinformatic and Biostatistics Unit of the Principe Felipe Research Center using the computational infrastructure supported by ERDF. Ontoria-Oviedo, I.; Dorronsoro, A.; Sánchez, R.; Ciria, M.; Gómez-Ferrer, M.; Buiges, M.; Grueso, E... (2018). Extracellular Vesicles Secreted by Hypoxic AC10 Cardiomyocytes Modulate Fibroblast Cell Motility. Frontiers in Cardiovascular Medicine. 5. https://doi.org/10.3389/fcvm.2018.00152