Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial-mesenchymal transformation of the epicardium

Previous research has revealed that cells contributing to coronary vascular formation are derived from the dorsal mesocardium, however, the fate of th ese cells during consecutive stages of heart development is still unclear. We have conducted a study regarding the recruitment of vascular components and the subsequent differentiation into mature vessel wall structures with the aid of immunohistochemical markers directed against endothelium, smooth muscle cells, and fibroblasts. The proepicardial organ including an adheri ng piece of primordial liver of quail embryos (ranging from HH15 to HH18) w as transplanted into the pericardial cavity of chicken embryos (ranging fro m HH15 to HH18). The chicken-quail chimeras (n=16) were harvested from the early stage of endothelial tube formation (HH25) to the late stage of matur e vessel wall composition (HH43). Before HH32 endothelial cells have invade d the myocardium to give rise to yet undifferentiated coronary vessels. The se endothelial cells are not accompanied by other non-endothelial cells. Th e superficial epicardial layer changes from a squamous mesothelium into a c uboid epithelium preceding media and adventitia formation. Subsequently, a condensed area of mesenchymal cells delaminates from the cuboidal lining ex tending toward the vessel plexus. Around the coronary arteries, these mesen chymal cells differentiate into smooth muscle cells or fibroblasts as shown by immunohistochemical markers. We conclude that epithelial-mesenchymal tr ansformation of the epicardial lining delivers the smooth muscle cells and fibroblasts of the coronary arterial vessel wall. Molecules involved in epi thelial transformation processes elsewhere in the embryo are also expressed within the subepicardial layer, and are considered to participate in induc ing this process.