The Epicardium and the Formation of the Coronary Vasculature

In early development the epicardium as an extracardiac organ envelops the initially bare myocardial surface. In this way, a three-layered organ is formed consisting of an inner endocardium, the muscular myocardium, and the covering epicardium (Manasek, 1969; Ho and Shimada, 1978; Viragh and Challice, 1981; Hiruma and Hirakow, 1988). The epicardium proved to be the source for novel cell populations migrating into the myocardial wall, which play major, but not yet fully comprehended, roles in heart development. It has been shown in a number of studies, using knockout mice, that when the epicardium is missing, the coronary vessels fail to develop properly (Kwee et al, 1995; Yang et al, 1995), usually leading to embryonic death at a very specific point in development. It must be concluded that the formation of the coronary vasculature is one of the features of heart development depending on epicardial differentiation. Therefore, we describe and discuss first the differentiation of the epicardial-derived cells (EPDCs), followed by the development of the endothelium that does not derive from the epicardial organ proper, and the smooth muscle cells and adventitial fibroblasts of the coronary vessel wall. Finally, we discuss the differentiation of the vascular tree, starting with a plexiform system of sinusoidal vessels, developing into arteries and veins, interconnected by a capillary network.