Beyond immunity: macrophage plasticity in vascular regeneration

Abstract Macrophages drive microvascular development, repair, and remodeling in addition to their roles in immunity. Single-cell transcriptomics reveals macrophage subpopulations whose vascular functions exceed the M1/M2 framework. Here we review four mechanisms of macrophage-driven angiogenesis—paracrine secretion, endothelial contact, matrix remodeling, and mural cell crosstalk—and their temporal ordering across development, injury, and disease. Finally, we examine translational strategies and propose a stage-resolved framework for driving revascularization or suppressing tumor angiogenesis.