ArticleCNS neuroscience & therapeutics2025
High Shear Stress-Induced Endothelial Piezo1 Downregulation Promotes Intracranial Aneurysm Formation via the PDGF-BB/PDGFRβ Paracrine Signaling Pathway.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The Influence of M1 and DLPFC iTBS on BCI Performance: A TMS and fNIRS Study.Translational stroke research · 2026Article
- Exercise-altered fluid shear stress regulates vascular endothelial inflammation via Piezo1.Frontiers in physiology · 2026Review
- From hemodynamic stress to inflammatory wall remodeling in intracranial aneurysms.Frontiers in molecular biosciences · 2026Review
- High Shear Stress-Induced Endothelial Piezo1 Downregulation Promotes Intracranial Aneurysm Formation via the PDGF-BB/PDGFRβ Paracrine Signaling Pathway.CNS neuroscience & therapeutics · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundAbnormally high shear stress (HSS) is strongly associated with intracranial aneurysm (IA) formation. Endothelial Piezo1 is sensitive to shear stress stimulation, but the mechanism by which it mediates this mechanobiological coupling process is unclear.
methodsThe correlation between shear stress and the Piezo1 expression was investigated using human IA samples and a parallel-plate flow chamber system. To determine the effects of endothelial Piezo1 on the phenotype of neighboring vascular smooth muscle cells (VSMCs) and IA formation, the CRISPR/Cas9 system was used to inhibit endothelial Piezo1 gene expression in vitro. Piezo1
resultPiezo1 expression correlated negatively with the shear stress in human IA. HSS reduced EC Piezo1 expression and promoted VSMC phenotypic transformation compared with physiological shear stress. Depletion of EC Piezo1 resulted in the VSMC phenotypic transformation and, more importantly, promoted aneurysmal vascular remodeling in the mouse IA model. The platelet-derived growth factor subunit B (PDGFB)_Platelet-derived growth factor receptor β (PDGFRβ) was identified as being involved in this process. Moreover, the PDGFRβ antagonist reversed the VSMC phenotypic transformation and attenuated IA progression. Mechanistically, Piezo1 depletion promoted PDGFB expression via YAP/β-catenin pathway.
conclusionHSS downregulates Piezo1 expression in ECs, which subsequently enhances PDGF-BB expression through the YAP/β-catenin signaling pathway. The elevated PDGF-BB facilitates phenotypic transition of VSMCs via PDGFRβ binding, ultimately contributing to IA formation.
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