Formation and Growth of Cardiac Lymphatics during Embryonic Development, Heart Regeneration, and Disease

The lymphatic system plays crucial roles in regulating fluid homeostasis, immune surveillance, and lipid transport. As is in most of the body's organs, the heart possesses an extensive lymphatic network. Moreover, a robust lymphangiogenic response has been shown to take place following myocardial infarction, highlighting cardiac lymphatics as potential targets for therapeutic intervention. Yet, the unique molecular properties and functions of the heart's lymphatic system have only recently begun to be addressed. In this review, we discuss the mechanisms underlying the formation and growth of cardiac lymphatics during embryonic development and describe their characteristics across species. We further summarize recent findings highlighting diverse cellular origins for cardiac lymphatic endothelial cells and how they integrate to form a single functional lymphatic network. Finally, we outline novel therapeutic avenues aimed at enhancing lymphatic vessel formation and integrity following cardiac injury, which hold great promise for promoting healing of the infarcted heart.