PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations

BACKGROUND: variations remains unknown, and more effective and specific inhibitors to combat AVM formation in patients are needed. METHODS: knockout mice, along with downstream PIEZO1 signaling. RESULTS: overexpression enhanced AVM formation induced by ALK1 ligand blockade. Mechanistically, PIEZO1 inhibition reduced elevated vascular endothelial growth factor receptor 2/AKT, ERK5-p62-KLF4, endothelial nitric oxide synthase, hypoxia, proliferation, and inflammation in ALK1-deficient endothelium. CONCLUSIONS: PIEZO1 expression and signaling are elevated in type 2 hereditary hemorrhagic telangiectasia. PIEZO1 blockade reduces AVM formation and alleviates cellular and molecular hallmarks of ALK1-deficient cells. This finding provides new insights into the mechanistic underpinnings of ALK1-related vascular diseases and identifies potential therapeutic targets to prevent AVMs.