Development of the coronary blood supply: changing concepts and current ideas

Earlier views of the development of the coronary vasculature included angiogenic budding and growth of arteries from the aortic sinuses and veins from the coronary sinus. The current concept begins with the establishment of the epicardium from the proepicardial organ, an outgrowth of the dorsal wall of the pericardial cavity. Capillaries form in a subepicardial mesenchymal population, extending as a plexus toward the truncus arteriosus and the atria. Multiple vessels grow from a peritruncal ring of capillaries, preferentially invading the newly formed aorta. In a process involving apoptotic changes of both the aortic wall and the invading capillaries, orifices open at the level of the aortic sinuses. Smooth muscle cells and pericytes, recruited from the surrounding mesenchyme, contribute to the vessel walls, and the definitive coronary artery pattern is established. Similar events are occurring on the venous side of the coronary circulation, following a slightly earlier time course. Multiple factors govern this process, including VEGF and FGF-1 stimulating vasculogenesis and angiogenesis, and the angiopoietins and their tyrosine kinase receptors modulating interactions between endothelial cells and the mural components. As remodeling of the capillary plexus and the coronary orifices progresses, TGF beta released by apoptotic cells or from other sources likely modulates VEGF and FGF-1, and also contributes to further apoptotic changes. A better appreciation of the controls of the mechanisms of coronary vessel development may direct further research in the prevention of arteriosclerosis and ischemic tissue injuries.