Development of Coronary Vessels

Coronary vessels are patterned by cells arising from multiple developmental origins during heart development. An early subepicardial plexus of coronary endothelial cells (CoECs) originates from sinus venosus endothelium at the inflow tract of the looped heart tube together with a subpopulation of CoECs arising from the proepicardium (PE). Around embryonic day E11.5, a second plexus forms around the base of the outflow tract, invades the wall of the aortic root, and forms the coronary stems. Precise positioning of right and left coronary stems depends on signaling by VEGF‐C and second heart field‐derived cardiac myocytes that form within the wall of the aortic root. Shortly after initiation of coronary blood flow at E13.5, smooth muscle cells (CoSMCs) begin to form the medial layer and express early differentiation markers. CoSMCs immediately surrounding the coronary stems arise from the aortic wall itself, while the vast majority of remaining CoSMCs are PE‐derived. By E17.5, differentiation of most CoSMCs is complete and the adventitial layer begins to form. Shortly after birth compaction of the trabeculated inner myocardium results in appearance of a late set of CoECs arising from endocardium. Hedgehog, Wnt and FGF signaling play important roles in physiological maintenance of postnatal coronary vessels. Restoration of coronary vasculature after cardiac injury is characterized by surprising plasticity of interstitial and adventitial fibroblasts and their conversion to endothelial and mural cells during coronary repair. [Support by NIH‐HL123650].