Mechanisms of infantile hemangioma involution (Review)

Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, characterized by a distinctive life cycle of rapid postnatal proliferation followed by spontaneous involution. However, the mechanisms underlying this regression process remain incompletely understood. In this narrative review, current IH-specific evidence was synthesized and candidate pathways were organized according to their relative strength. A total of three core mechanistic modules with moderate-to-high supporting evidence were identified: Endothelial proliferation restraint, immune microenvironment remodeling and adipogenic differentiation of hemangioma-derived progenitor cells. Additional pathways, including extracellular matrix remodeling, regulated cell death and endocrine signaling, were discussed as potential contributors but remain less validated. Overall, IH involution appears to represent an active and coordinated process of immunovascular remodeling rather than passive regression. Future studies should prioritize longitudinal human samples, single-cell and spatial profiling and functional validation in immune-competent models to clarify the temporal hierarchy and causal interactions among these pathways.