Vascularizing the heart.

As the developing heart grows and the chamber walls thicken, passive diffusion of oxygen and nutrients is replaced by a vascular plexus which remodels and expands to form a mature coronary vascular system. The coronary arteries and veins ensure the continued development of the heart and facilitate cardiac output with progression towards birth. Many aspects of coronary vessel development are surprisingly not well understood and recently there has been much debate surrounding both the developmental origin and tissue contribution of cardiovascular cells alongside the specific signals that determine their fate and function. What is clear is that an understanding of the cellular and molecular cues to vascularize the heart of the embryo has significant implications for adult heart disease and regeneration, as we move towards targeted cell-based therapies for neovascularization and coronary bypass engraftment. This review will focus on the proposed cellular origins for the coronary endothelium with due consideration to the pro-epicardial organ/epicardium, sinus venosus and endocardium as potential sources, and we will explore the outstanding questions and technical limitations with respect to accurate labelling and lineage tracing of the developing coronaries. We will briefly document canonical vascular signalling that induces vessels in the heart alongside a focus on the potential for developmental reprogramming and putative mechanisms underpinning venous vs. arterial cell fate. Finally, we will extrapolate directly from development to address adult maintenance of the coronaries, vascular homeostasis and remodelling in response to pathology, aligned with the potential for revascularizing the injured adult heart.