Estradiol Inhibits Human Brain Vascular Pericyte Migration Activity: A Functional and Transcriptomic Analysis

Stroke is the third leading cause of mortality in women and it kills twice as many breast cancer. A key role pathophysiology stroke plays disruption blood–brain barrier (BBB) within neurovascular unit. While estrogen induces vascular protective actions, its influence on remains unclear. Moreover, experiments assessing impact endothelial cells to induce integrity are non-conclusive. Since pericytes play an active regulating BBB function, we hypothesize that estradiol may by their activity. In this study using human brain (HBVPs) investigated pericyte functions known integrity. HBVPs expressed receptors (ER-α, ER-β GPER) treatment with (10 nM) inhibited basal cell migration but not proliferation. a hallmark for following injury, infection inflammation, effects TNFα-induced PC migration. Importantly, prevented effect was mimicked PPT (ER-α agonist) DPN (ER-β agonist), G1 (GPR30 agonist). The modulatory were abrogated MPP PHTPP, selective ER-α antagonists, respectively, confirming mediating anti-migratory actions estrogen. To delineate intracellular mechanisms inhibitory migration, AKT MAPK activation. consistently reduced Akt phosphorylation, only inhibition MAPK, Akt, significantly migratory TNFα. transendothelial electrical resistance measurements, induced function (TEER) microvascular co-cultured pericytes, HBMECs cultured alone. transcriptomics analysis genes modulated showed downregulation increase upregulation inhibit Taken together, our findings provide first evidence modulates activity thereby improves