摘要：SummaryBlood and lymphatic vessels surrounding the heart develop through orchestrated processes from cells of different origins. In particular, cells around the outflow tract which constitute a primordial transient vasculature, referred to as aortic subepicardial vessels, are crucial for the establishment of coronary artery stems and cardiac lymphatic vessels. Here, we revealed that the epicardium and pericardium-derived Semaphorin 3E (Sema3E) and its receptor, PlexinD1, play a role in the development of the coronary stem, as well as cardiac lymphatic vessels.In vitroanalyses demonstrated that Sema3E may demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells, resulting in proper coronary and lymphatic vessel formation. Furthermore, inactivation of Sema3E-PlexinD1 signaling improved the recovery of cardiac function by increasing reactive lymphangiogenesis in an adult mouse model of myocardial infarction. These findings may lead to therapeutic strategies that target Sema3E-PlexinD1 signaling in coronary artery diseases.Graphical abstractDisplay OmittedHighlights•Sema3E-PlexinD1 signaling regulates coronary and cardiac lymphatic vessel development•Sema3E demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells•Inhibition of Sema3E-PlexinD1 signaling improves the recovery after myocardial injuryBiological Sciences; Cell Biology; Developmental Biology
