Flow induced-endothelial phenotypic transition contributes to Intracranial Aneurysm

Elucidating the pathological mechanisms driving IA initiation and progression is critical for developing an effective therapeutic strategy. Endothelial cell (EC) dysfunction is known to contribute to IA pathogenesis.

Hemodynamic force— particularly fluid shear stress (FSS) are well-established mediators of IA pathogenesis, yet the mechanisms by which FSS triggers endothelial injury remain incompletely understood. In this study, single-cell sequencing of human revealed that endothelial-to-mesenchymal transition (EndMT) as a hallmark feature of early-stage IA formation, whereas EndMT was markedly attenuated in ruptured aneurysms. Using a mouse IA model and an in vitro parallel-plate flow chamber system, we demonstrated that exposure to high laminar FSS (HSS) promotes EndMT in endothelial cells, concomitant with actin cytoskeletal reorganization and nuclear translocation of Yes-associated protein (YAP).