Towards Consensus on Coronary Vessel Development

Coronary heart disease remains a leading cause of morbidity and mortality, and as such, there is a pressing need to develop efficacious therapies. Any future cell-based therapeutic interventions aimed at revascularization of an ischemic heart, or regeneration of damaged coronary vessels, require a clear understanding of the developmental programs that are in place in the embryo. This knowledge will also be necessary to provide the basis for biologically engineered heart tissues. Despite intensive investigation into the development of the coronary vasculature, the embryonic origin of these cell types has remained unclear. In the 1990s, pioneering experiments by Mikawa and others using the avian embryo demonstrated that coronary vascular smooth muscle cells are derived from the proepicardium, a transient embryonic structure that emanates from the pericardial serosa adjacent to the sinus venosus external to the linear heart tube that gives rise to the epicardium. Subsequently, the proepicardium was found to contribute interstitial cardiac fibroblasts, atrioventricular cushion cells, cardiac stem cells, and, at least in avian species, some coronary endothelial cells (ECs). The notion that some cardiomyocytes have an epicardial or proepicardial origin has diminishing support, and was likely to be caused by ectopic or misexpression of transgenic lineage tracing tools used, leading to incorrect conclusions.