Background: An intricate network of cardiac blood and lymphatic vessels provide cardiac tissue with oxygen and nutrients while eliminating excess fluid from the interstitium. These functions are indispensable for heart function and so identifying factors that can encourage the formation of coronary and cardiac lymphatic vessels is of critical therapeutic importance.
Purpose and Methods: We wish to understand how to encourage the formation of coronary vasculature by understanding how it developments and regenerates. By observing these processes in the zebrafish we can identify the key contributing cells types and their interactions, and ultimately what factors guide them. In this study, using our imaging technology and available genetic mutant and transgenic lines, we have established the zebrafish as a developmental model of coronary vessel formation and find that this is concomitant with that of the cortical myocardium, and later cardiac lymphatic system, development.
Results and Conclusion: The heart becomes vascularized in two post-embryonic waves. First, coronary endothelial cells migrate over the ventricle as the outer cortical layer of the myocardium is forming. These endothelial cells then organize to form a network of vessels intertwined within this cortical layer. Second, lymphatic endothelial cells use this coronary network as a scaffold to migrate down over the ventricle to form lymphatic vessels in close proximity to the coronary arteries. Both these processes temporally utilize CXC-chemokine signaling to guide them, providing a promising insight into how this might be encouraged therapeutically.