Fig. 5

The role of macrophages during cardiac development. Macrophages first appear during mouse embryo development around E10 near the outflow tract, sinus node, and endocardial cushions. As the heart matures, they are distributed beneath the epicardium, within the myocardial layer, and in the endocardial layer throughout the entire heart. Various macrophage subpopulations have been identified at different times and locations, with significant research focused on subepicardial space subpopulations (CX3CR1⁺ CD68⁺ F4/80⁺ Lyve-1^+/-; CX3CR1high CD64⁺ Lyve-1⁺ CCR2^-). These macrophages originate from the yolk sac and migrate to the epicardium under the influence of the transcription factor WT1, subsequently entering the subepicardial space. In the subepicardial space, these macrophages adhere to the endothelial cells of blood vessels, promoting the normal development of coronary arteries. Simultaneously, they adhere to the endothelial cells of lymphatic vessels and facilitate normal lymphatic development through direct interactions involving hyaluronic acid. Macrophages within endocardial cushions (Nfatc1⁺ CD45⁺ CD68⁺ F4/80⁺ CD206⁺), derived from endothelial cells, likely contribute to valve development through phagocytic activities. CCR2 C-C chemokine receptor type 2, CX3CR1 chemokine (C-X3-C motif) receptor 1, Lyve-1 lymphatic vessel endothelial hyaluronan receptor 1, Nfatc nuclear factor of activated T cells, cytoplasmic, WT1 Wilms tumor 1. This figure was created using Adobe Illustrator