Extracellular Vesicles Secreted by Hypoxic AC10 Cardiomyocytes Modulate Fibroblast Cell Motility

Autores de CIPF

• Imelda Ontoria Oviedo

  Autor

• Akaitz Dorronsoro González

  Autor

• Rafael Sánchez Sánchez

  Autor

• Maria Ciria Calduch

  Autor

• Marta Gómez Ferrer

  Autor

• Sandra Tejedor Gascón

  Autor

• 

  Francisco García García

  Autor

• Hernán González-King

  Autor

• Pilar Sepulveda Sanchis

  Autor

Participantes ajenos a CIPF

• Buigues M
• Grueso E
• Garcia NA
• Peiró-Molina E

Grupos de Investigación

• Unidad de Bioinformática y Bioestadística

  

  Jefe/a de Grupo

  Francisco García García

Abstract

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 cardiornyocyte 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.

Keywords

• cardiomyocytes; fibroblasts; endothelial cells; extracellular vesicles; hypoxia; cellular communication