Abstract
Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43–56 days) were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin), CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.
Highlights
The growth of the vascular system during development involves sprouting, migration and proliferation of endothelial cells (ECs) [1]
Sprouting angiogenesis is guided by a distinctive celltype, the endothelial tip cell (ETC) [1,2,3,4,5,6,7] and is promoted by pro-angiogenic signals such as vascular endothelial growth factor (VEGF), that controls whether specific ECs become ETCs or trailing stalk cells [8, 9]
Mostly on the ventral surface and distally, towards the apex cordis, we found large successive vascular canals covered by epicardial mesothelium; the walls of these canals that appeared to be blood islands, were strongly vimentin-positive and were apparently involved in processes of sprouting angiogenesis (Fig. 1)
Summary
The growth of the vascular system during development involves sprouting, migration and proliferation of endothelial cells (ECs) [1]. Sprouting angiogenesis is guided by a distinctive celltype, the endothelial tip cell (ETC) [1,2,3,4,5,6,7] and is promoted by pro-angiogenic signals such as vascular endothelial growth factor (VEGF), that controls whether specific ECs become ETCs or trailing stalk cells [8, 9]. It was considered that endocardial ECs form a large sheet without angiogenic sprouting into the myocardium [15]. The endocardial cells are not terminally differentiated, but are angiogenic capable and able to form coronary endothelial networks [16]. The valuable contribution of these authors was analyzed and was considered that further work is needed in order to evaluate the contributions to the coronary tree brought by the endocardium, the proepicardium and the sinus venosus [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
