Endocardial Cells Form the Coronary Arteries by Angiogenesis through Myocardial-Endocardial VEGF Signaling

Abstract

Summary The origins and developmental mechanisms of coronary arteries are incompletely understood. We showed here by fate mapping, clonal analysis and immunohistochemistry that endocardial cells generate the endothelium of coronary arteries. Dye tracking, live imaging, and tissue transplantation also revealed that ventricular endocardial cells are not terminally differentiated; instead, they are angiogenic and form coronary endothelial networks. Myocardial Vegf-a or endocardial Vegfr-2 deletion inhibited coronary angiogenesis and arterial formation by ventricular endocardial cells. In contrast, lineage and knockout studies showed that endocardial cells make a small contribution to the coronary veins, the formation of which is independent of myocardial-to-endocardial Vegf signaling. Thus, contrary to the current view of a common source for the coronary vessels, our findings indicate that the coronary arteries and veins have distinct origins and are formed by different mechanisms. This information may help develop better cell therapies for coronary artery disease.

Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

“…A careful analysis of this study suggests that the sinus venosus endocardium, which is able to vascularize subepicardial and myocardial heart layers, mainly provides a cellular scaffold for the development of coronary veins (CoV). Accordingly, a second source of coronary endothelium (CoE) has been identified in the ventricular endocardium (Nfatc1 + lineage), which contributes massively to coronary arterial (CoA) endothelium (3,6).…”

Probing chromatin landscape reveals roles of endocardial TBX20 in septation

“…Notably, we also observed these migratory defects by using a more endocardium-restricted Cre line, Nfatc1-Cre (16), to ablate Tbx20 (Supplemental Figure 3, A and B).…”

Revascularisation du cœur après un infarctus

“…Une prolifération importante des cellules endocardiques et des muscles lisses sous-jacents accompagne cette angiogenèse. Ces vaisseaux acquièrent spécifique de l'endocarde, et qui s'organise pour former des vaisseaux sous l'influence du facteur de croissance VEGF (vascular endothelial growth factor) et de l'expression de son récepteur VEGFR2 (vascular endothelial growth factor receptor 2) [8]. Enfin, une dernière étude montre que l'endocarde est la source majeure des vaisseaux coronaires qui se développent tardivement, juste après la naissance, lorsque les trabécules se compactent pour former un muscle cardiaque lisse et efficace [9].…”