Endothelial Cell-Pericyte Crosstalk in the Brain Balances Microvascular Stability and Plasticity.

Pericytes are mural cells that broadly support microvascular integrity and are essential contributors to the neurovascular unit in the brain. They contribute to blood-brain barrier function, endothelial behavior, and microvascular tone, and their dysfunction is implicated in cardiometabolic and neurovascular disease. However, pericytes remain difficult to directly manipulate due to heterogeneous identity, overlapping marker expression with other mural and stromal cells, and context-dependent functional behaviors. Here, we propose that pericytes are best understood as dynamic regulators of microvascular state rather than a static cell type. Pericyte behaviors span a spectrum of functional states associated with vascular stability, angiogenesis, contractility, and fibrosis, and transitions between these functions shape microvascular remodeling in development, homeostasis, and disease. In their stabilization state, pericytes support blood-brain barrier integrity and microvascular stability, and when disrupted, can contribute to small vessel disease and neurodegeneration. Conversely, a plastic pericyte state is often associated with angiogenesis and ischemia-reperfusion responses, but can also contribute to fibrotic remodeling. Finally, we discuss how experimental systems, including in vitro and in vivo models, inform the interpretation of pericyte function and state. This perspective provides a framework for interpreting pericyte biology in the context of endothelial cell function and suggests that targeting pericyte state dynamics may offer new opportunities to protect the microvasculature in response to cardiometabolic and neurovascular disease.