Development of novel zebrafish models to analyse endogenous extracellular vesicle trafficking during the cardiac injury response and subsequent regeneration
Extracellular vesicles, including exosomes (30 - 120 nm) and microvesicles (>120 nm), are released from the plasma membrane of cells and can contain nucleic acids (particularly microRNAs), proteins and lipids. EVs can induce short and long-range/systemic functional responses in targeted recipient cells. In humans, exosomes containing cardiovascular microRNAs populate the pericardial fluid and heart injury increases exosome number in the peripheral blood. EVs are vital cell-cell communication mediators and may be valuable as novel therapeutic delivery vehicles, but our knowledge of in vivo EV trafficking in homeostasis and during cardiovascular disease remains poor. This project helped establish techniques to visualise endogenous EVs in vivo in the pericardial space and peripheral blood using transgenic zebrafish lines to stably label cardiomyocyte- and endothelial-cell derived EVs. We can extract these different populations of EVs and we have obtained a studentship to determine the functional effects of these EVs following cardiac injury.