Endothelial-Mesenchymal transition in cerebrovascular diseases: molecular mechanisms and promising pharmacological strategies.
Endothelial-mesenchymal transition (EndMT) is a critical process in cerebrovascular diseases, contributing to vascular instability, fibrosis, and inflammation. This review summarizes the molecular mechanisms driving EndMT-including TGF-β, Wnt, Notch pathways, inflammation, oxidative stress, and hemodynamics-and its role in specific conditions such as cerebral cavernous malformations, brain arteriovenous malformations, and moyamoya disease. We also evaluate promising pharmacological strategies, including statins, antihypertensives, antidiabetic drugs, and anti-inflammatory agents, that show efficacy in preclinical models. However, clinical translation remains challenging due to issues of specificity, drug delivery across the blood-brain barrier, and disease heterogeneity. Future directions emphasize biomarker-driven approaches and endothelial-specific therapies to bridge mechanistic insights into clinical applications.