Myocardial regeneration: role of epicardium and implicated genes

Lower invertebrates' hearts such as those of zebrafish have the capacity for scarless myocardial regeneration which is lost by mammalian hearts as they form a fibrotic scar tissue instead of regenerating the injured area. However, neonatal mammalian hearts have a remarkable capacity for regeneration highlighting conserved evolutionary mechanisms underlying such a process. Studies investigated the underlying mechanism of myocardial regeneration in species capable to do so, to see its applicability on mammals. The epicardium, the mesothelial outer layer of the vertebrate heart, has proven to play an important role in the process of repair and regeneration. It serves as an important source of smooth muscle cells, cardiac fibroblasts, endothelial cells, stem cells, and signaling molecules that are involved in this process. Here we review the role of the epicardium in myocardial regeneration focusing on the different involved; Activation, epithelial to mesenchymal transition, and differentiation. In addition, we will discuss its contributory role to different aspects that support myocardial regeneration. Of these we will discuss angiogenesis and the formation of a regenerate extracellular matrix. Moreover, we will discuss several factors that act on the epicardium to affect regeneration. Finally, we will highlight the utility of the epicardium as a mode of cell therapy in the treatment of myocardial injury.