Resident cells of the myocardium: more than spectators in cardiac injury, repair and regeneration

Figures

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  Figure 1. New blood vessel formation and maturation requires communication between endothelial cells (ECs) and pericytes (PCs) through paracrine factors. (a) A quiescent capillary: cell–cell contact between ECs (in white) and PCs (in yellow) maintains capillaries in a quiescent state, in part through the actions of pericyte derived angiopoetin 1 (Ang 1) on EC Tie 2 receptors. (b) Cardiac injury (MI) triggers neovascularisation (from pre-existing adult ECs — in pink) and ECs release Ang 2 that prevents access of Ang 1 to EC Tie 2 receptors and allows EC sprouting and pericyte detachment. Sprouting ECs also release MMPs that promote pericyte detachment and EC migration. (c) PDGFB is released by ECs during the elongation process. Pericytes expressing the PDGFRβ are recruited to stabilize and mature the new vessels (d). Maturation is also promoted by the binding of Ang 1 to pericyte Tie 2 receptors.

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  Figure 2. Roles of resident macrophages in physiology and in pathophysiology following MI. Yolk-sac and fetal liver (YS/FL) derived macrophages that predominate in the neonatal mouse heart are gradually replaced over the lifetime by bone-marrow (BM) derived macrophages that may provoke a greater inflammatory response to injury. Macrophages have a phagocytic role in the healthy mouse heart and in the atrio-ventricular conducting system are required for electrical signaling. Following MI, macrophages are required for angiogenesis in neonatal and adult mice, and may have a role in regulating cardiomyocyte proliferation under hypoxic conditions, at least in neonates. Macrophages are important for scar removal in neonatal mice to ensure scar free regeneration, but influence fibroblast activation in the adult to ensure formation of a replacement scar in the absence of efficient regeneration.