The origin of the epicardium and the embryonic myocardial circulation in the mouse

Abstract

The origin of the epicardium and the formation of the early blood vessels of the heart prior to the opening of the coronary arteries from the aorta have been studied in the 9-13.5 day post coitum (dpc) mouse embryo heart. The epicardium begins to appear by 9 dpc. The majority of the epicardial cells derive from the somatopleural investment of the septum transversum, from where they migrate, associated to form vesicles, to the dorsal aspect of the ventricles and atria. The epicardial cells then migrate over the lateral surfaces and the AV sulcus to the ventral aspect of the heart. In the subepicardial space around the sulci, the proliferating epithelial tissue is found, also in vesicular form, for a time. The ventrally migrating primordial epicardial tissue ensheaths lastly the truncus arteriosus, while the sinus venosus is coated with epicardium ab initio, where (and also in the SA sulcus) the epicardial cells derive in part from the cuboidal cells of the pleuroperitoneal canal and in part from the somatopleural cells. The early blood vessel formation follows in space and time the development of the epicardium. The first blood vessels appear by dpc by the invagination of the endocardium into the early sinus muscle, and at the same time in the ventricular chamber by the encasing of the endocardium, as the trabeculae become consolidated into the myocardial walls. By this process sinusoids are formed, some of which penetrate through the myocardium and which, by rapid proliferation, form an interconnected subepicardial plexus. These capillaries proliferate ventrally in the wide subepicardial space, reaching the septating truncus, in which the aorta and pulmonary artery are developing. The definitive coronary artery openings appear by 13 dpc, allowing the high pressure blood from the aorta to flow into a preexisting vascular bed.

Vasculogenesis of the embryonic heart: Origin of blood island‐like structures

“…When the tissue attaches to the heart, it is no longer considered to be the proepicardium but the epicardium and its derivative, subendocardial mesenchyme. Thus, the presence of hematoblasts or NRBCs detected by Virá gh et al referred to their location in the subepicardium at the onset of heart vascularization (Virá gh and Challice, 1981;Virá gh et al, 1993), which has been consistent with our observation.…”

“…These structures assemble in clusters prior to their presumed coalescence and differentiation into vascular channels (Tomanek et al, 1996). Blood island-like structures are located within the myocardial wall and the subepicardium of 10 and 11 dpc mice (Virá gh and Challice, 1981). They are encountered within 13 dpc rat hearts (Rongish et al, 1994;Ratajska and Fiejka, 1999).…”

“…Hearts devoid of the epicardium do not develop vascular channels (Kwee et al, 1995). The epicardium derives from an extracardiac source (Kurkiewicz, 1909): proepicardial villi, which form on the ventral surface of the sinus venous horns as cellular protrusions growing toward the pericardial cavity and reaching the opposite surface of the looping heart (dorsal atrioventricular sulcus) (Ho and Shimada, 1978;Virá gh and Challice, 1981;Kuhn and Liebherr, 1988;Hiruma and Hirakow, 1989;Mä nner, 1992;Virá gh et al, 1993;Mä nner et al, 2001). The proepicardium subsequently spreads over the surface of bare myocardium, giving rise to the epicardium and the subepicardial mesenchyme.…”

PDGF‐A as an epicardial mitogen during heart development

“…In response to factors secreted by the myocardium, cells in the epicardium then undergo an epithelial-mesenchymal transformation (EMT) to create subepicardial mesenchyme from which ventricular fibroblasts and cells of the coronary vasculature (endothelium and smooth muscle) are derived. These cells invade the thickening ventricular wall and organize into a coherent arterial network that becomes connected to systemic circulation around E14 (Viragh and Challice, 1981). It is widely assumed that the imposition of coronary circulation is required for continuing heart and embryonic growth once the thickness of the ventricular wall becomes diffusion-limited.…”

Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos

“…Morphologic and experimental studies point to a transitory structure, the proepicardium (PE), a grape-like cluster of mesothelial cells derived from the pericardial serosa that extends to and migrates over the myocardial surface during the looping, tubular stage of heart development (Manasek, 1969;Ho and Shimada, 1978;Viragh and Challice, 1981;Komiyama et al, 1987;Kuhn and Liebherr, 1988;Fransen and Lemanski, 1990;Manner, 1992;Mikawa and Fischman, 1992;Viragh et al, 1993;Munoz-Chapuli et al, 1994;Mikawa and Gourdie, 1996).…”