What Is the Role of Endothelial Cells in Cerebral Blood Flow Dysregulation in Small Vessel Disease?

Endothelial cells are a critical component of the neurovascular unit (NVU). They express ion channels and receptors that sense multiple signals, including shear stress and increased extracellular potassium (K⁺) resulting from neuronal activity. They release several mediators that regulate cerebral blood flow and promote vasodilation, particularly nitric oxide, thereby contributing to neurovascular coupling (functional hyperemia). Endothelial cells are connected through tight junctions and are crucial for the formation and maintenance of the blood-brain barrier. They are particularly susceptible to senescence, and their dysfunction has a key role in NVU dysregulation in cerebral small vessel disease.