As the study of coronary morphogenesis enters the era of molecular biology, there are 3 major questions that at present dominate the field: What determines the pattern by which the branches of the coronaries emerge normally from the aorta? What are the antecedents of the coronary vasculature and the molecular mechanisms by which they are formed? What is the nature of the inductive interactions between cellular precursors of the developing coronary vasculature and those associated with development of the myocardium? For example, a question that has recently emerged is whether the spatial relationship between developing coronary arterioles and developing myocardial tissues serves to direct myocardial differentiation into the peripheral conduction system.
These questions and others are considered in the following 4 papers, which constitute a synthesis of the basic structural and molecular elements of coronary morphogenesis. What emerges from these papers is a consensus that the epicardium and its progenitor, the proepicardial organ, play a major but not necessarily exclusive role in forming the mesenchymal precursors that assemble and differentiate into vascular tissues. In reviewing how this occurs at a molecular level and what morphogens (for example, VEGF, FGF, TGF, and endothelin) and extracellular ligands (VCAM, fibulin) drive coronary vasculogenesis, our contributors do so with the understanding that the assembly of coronary vessels is a vasculogenic (and not an angiogenic) process. By this it is meant that the coronaries are assembled from free mesenchymal cells rather than by branching from existing vessels.
Clearly much has been learned; but the information provided by our authors holds perhaps even more significance for the future, because the fundamental steps in the process of coronary vasculogenesis that they identify can now be further explored using gene chips and microarrays, combined with laser capture and conditional gene knockouts and knockins. These technologies hold the potential to reveal a characteristic gene profile that will define the cascade of genetic and protein expressions that occurs during the epithelial-to-mesenchymal transformation and the subsequent migratory cell:cell adhesions and differentiation pathways that underlie the coronary morphogenetic process. These baseline principles of coronary morphogenesis will also naturally extend into gene and tissue engineering with the goal of replacing or repairing diseased coronary structures or the tissues that they vascularize. The authors of this series of papers will undoubtedly be looked upon as the pioneers of coronary vasculogenesis, whose current work continues to lead the field.