Innate immune cells such as macrophages and neutrophils have special abilities that enable them to rapidly gather in large numbers at the site of infection or injury. A recent study shows that in adult ischemic muscle, macrophages trigger a change in phenotype in mural cells, which helps restore functional blood flow and promote healing. This discovery highlights macrophages as a potential target for enhancing vascular integrity and healing of ischemic injuries.Masses of cells congregate at the location of infection or injury. According to a new study by researchers at Uppsala University, macrophages in the adult ischemic muscle undergo a change in phenotype to support the restoration of functional blood flow and promote healing. This discovery identifies macrophages as a potential target for enhancing vascular integrity and healing of ischemic injuries. Manifestations of cardiovascular diseases are a result of impaired tissue perfusion, leading to injury and loss of tissue function. The rapid restoration of functional blood flow is crucial for these conditions.Ischemic injury occurs following a lack of blood flow to a certain area, causing damage to the tissues. It is important to limit this damage and allow for healing and the restoration of function. When an ischemic event occurs, immune cells, such as macrophages, quickly gather at the affected site to aid in tissue regeneration and restructuring.
In cases of injured muscle, such as the human infarcted myocardium, macrophages have been observed to gather in perivascular locations, where they take on a more elongated shape and support the newly formed vasculature. This change in cellular morphology is similar to that of mural cells, which play a crucial role in maintaining blood flow by reducing vascular leakage.The article discusses the potential role of macrophages in promoting vessel maturation in injured muscle. The study, published in Nature Cardiovascular Research, found that macrophages in ischemic muscle upregulated proteins associated with mural cells and downregulated those associated with immune cell functions. Single-cell RNA-sequencing of fate-mapped macrophages identified a subpopulation that shifted their gene expression from macrophage markers to mural cell markers like PDGFRβ. This suggests that macrophages may take on mural cell functions to improve healing in injured muscle.In injured tissues, macrophages were found to undergo a transformation into cells with a similar appearance, genetic profile, and function as mural cells. This change was shown to be functionally relevant, as blocking the macrophage-specific PDGFRβ gene prevented them from taking on their perivascular macrophage role. This led to impaired vessel maturation, increased vessel leakiness, and ultimately reduced limb function. Therefore, in addition to their morphological and genetic changes, macrophages in injured tissues also take on important functions of mural cells in the healing process of ischemic injuries. the study demonstrated that macrophages in adult ischemic tissue undergo a cellular program to become more like mural cells while weakening the tissue.The change in macrophage identity is important for restoring tissue function, as it shows that immune cells in adult tissue can take on the roles of other cell types to help repair tissue. This discovery could be a potential target for immunotherapies to improve healing.
