Pericytes as key mediators of microenvironmental signaling crosstalk: implications in vascular diseases and cancer

Pericytes are important components of microenvironmental signaling interactions within the microvascular wall and participate in maintaining vascular stability and regulating endothelial function. They are increasingly recognized as important components of the vascular microenvironment rather than isolated structural cells. Under physiological conditions, they integrate biochemical, mechanical, and immune signals to preserve vascular barrier integrity and support vessel remodeling, functioning as one component of a broader multicellular network that includes endothelial cells, astrocytes, smooth muscle cells, immune cells, and extracellular matrix components. Pathological stimuli including metabolic stress, ischemia, or oncogenic signaling disrupt these regulatory networks. As a result, pericy-mediated interactions undergo adaptive remodeling, contributing to diverse vascular phenotypes. These range from hyperpermeability in retinal and neurovascular disorders to structurally and functionally abnormal tumor vasculature. In this review, we explore the mechanisms by which pericytes participate in signaling crosstalk in health and disease, emphasizing their interactions with endothelial cells, immune cells, and extracellular matrix components. Additionally, we provide an overview of the potential therapeutic implications of targeting pericyte-mediated signaling to restore crosstalk balance and achieve vascular normalization. These approaches position pericytes as important signaling nodes within microenvironmental signaling networks and provide a conceptual foundation for more effective interventions in vascular diseases and cancer.