Extracellular vesicles as cardiac immunomodulators

Extracellular vesicles (EVs) are nanoparticles released by cells in the body, carrying proteins, genetic material, and other signals that allow cells and organs to communicate. In the heart, EVs help coordinate this communication under normal conditions and during disease, such as a heart attack. Despite their recognized importance, much remains unknown about how EV production is regulated and how EVs influence cardiac disease. EVs released by stem and progenitor cells have also emerged as promising tools for cardiac repair, though how exactly they protect the heart is not yet fully understood.
In this thesis, we showed that EV production by human heart muscle cells is highly sensitive to the surrounding environment. Low oxygen levels and inflammatory signals each triggered EV release through distinct molecular pathways. We also identified three subtypes of these vesicles with different protein compositions, and found that one subtype released under low-oxygen conditions could drive immune cells toward a more inflammatory state, which could have potential consequences for healing after a heart attack. We also showed that certain viral infections can hijack EV production, leading to the release of virus-containing vesicles that may facilitate viral spread within the heart.
In the second part of this thesis, we studied EVs derived from cardiac progenitor cells as a potential therapy following a heart attack. We found that these vesicles influenced immune cell behavior, suggesting that further investigation is needed before such therapies can be effectively developed.
Together, these findings deepen our understanding of how stress, injury, and infection shape EV release, content, and function in the heart, and highlight the importance of thorough EV characterization before EV-based therapies can reach the clinic.