Characterisation of the pro-angiogenic properties of endogenous cardiac extracellular vesicle delivered microRNAs during heart injury and repair in zebrafish

Extracellular vesicles, including exosomes (30 - 120 nm) and microvesicles (microparticles, >120 nm), are released from the plasma membrane of cells and can contain nucleic acids (particularly microRNAs), proteins and lipids. EVs protect their molecular cargo from degradation so can induce short and long-range/systemic functional responses in targeted recipient cells. We have shown that human exosomes containing cardiovascular miRs populate the pericardial fluid and that heart ischaemia/reperfusion injury increases exosome number in the peripheral blood. Moreover, pericardial fluid exosomes are taken up by endothelial cells and induce vascular protection and angiogenesis via the transfer of miR let-7b-5p. EVs are emerging as vital cell-cell communication mediators and may be valuable as novel therapeutic delivery vehicles, however our knowledge of in vivo EV trafficking in homeostasis and during cardiovascular disease remains poor. This studentship will characterise zebrafish cardiovascular EV trafficking and determine pro-angiogenic miR transfer by EVs in vivo and in vitro.