Figure 3.

The phases of zebrafish cardiac regeneration. The uninjured heart contains a quiescent endocardium and epicardium, and a healthy myocardial layer. Following cardiac injury, the inflammatory phase takes place. Leucocytes are recruited to the injured area to remove necrotic and apoptotic cells and debris. Additionally, the endocardium and epicardium become activated and the first neovessels infiltrate the injury at the injury border zone (the interface between the injured myocardium and healthy myocardium). During the reparative phase, EPDC, synthetic mural cells and fibroblasts produce an extra-cellular matrix scaffold consisting of a collagen rich core and a fibrin cap. The dynamic signalling and activity of the epicardium and endocardium help coordinate the growth of new blood vessels and support the proliferation of existing cardiomyocytes at the injury border. Next, during the regenerative phase, proliferating cardiomyocytes repopulate the injured area and the fibrotic deposits are gradually removed. Finally, the endocardium and epicardium return to a quiescent state and the final maturation ensures the complete removal of scar tissue, restoration of cardiac function, and synchronicity. Figure created with BioRender.com.