Extracellular Vesicles and Intercellular Communication: Challenges for In Vivo Molecular Imaging and Tracking.

Extracellular vesicles (EVs) are a heterogeneous class of cell-derived membrane vesicles released by various cell types that serve as mediators of intercellular signaling. When released into circulation, EVs may convey their cargo and serve as intermediaries for intracellular communication, reaching nearby cells and possibly also distant organs. In cardiovascular biology, EVs released by activated or apoptotic endothelial cells (EC-EVs) disseminate biological information at short and long distances, contributing to the development and progression of cardiovascular disease and related disorders. The significance of EC-EVs as mediators of cell-cell communication has advanced, but a thorough knowledge of the role that intercommunication plays in healthy and vascular disease is still lacking. Most data on EVs derive from in vitro studies, but there are still little reliable data available on biodistribution and specific homing EVs in vivo tissues. Molecular imaging techniques for EVs are crucial to monitoring in vivo biodistribution and the homing of EVs and their communication networks both in basal and pathological circumstances. This narrative review provides an overview of EC-EVs, trying to highlight their role as messengers of cell-cell interaction in vascular homeostasis and disease, and describes emerging applications of various imaging modalities for EVs visualization in vivo.