The epicardium is a very dynamic cardiac layer with pivotal contributions during cardiogenesis,
acting in the postnatal period as an apparently dormant single-cell layer. In mammalian
embryos, the epicardium, which originates form the proepicardium, translocates into the pericardial
cavity and subsequently rests on the surface of the myocardium. Later, it gives rise to the epicardiumderived
cells, which migrate into subepicardial space, invade the developing myocardium, promoting
its growth, and contribute to different cell types. Anomalies in the process of epicardial development,
the generation of epicardium-derived cells and their signaling mechanisms in different experimental
models lead to defective cardiac development, reminiscent of human congenital heart diseases.
Furthermore, recent studies have reported that epicardial derivates in adults, i.e., epicardial adipose
tissue, are associated with electrophysiological cardiovascular anomalies. Herein, we provide a
state-of-the-art review focusing on both congenital and adult heart diseases associated with epicardial
development.
