Nitazoxanide activates BMP9-ALK1-SMAD signaling cascade and improves HHT vascular pathology

Objective: Hereditary hemorrhagic telangiectasia (HHT) is a vascular genetic disorder caused by endothelial cell dysfunction and characterized by telangiectasias and arteriovenous malformations (AVMs). HHT results primarily from loss-of-function mutations affecting components of the BMP9-ALK1-ENG-SMAD signaling cascade, a pathway essential for endothelial quiescence and vascular homeostasis, and currently lacks a cure. Here, we investigated whether nitazoxanide, an orally bioavailable drug with extensive clinical use, can modulate endothelial signaling relevant to HHT. Approach and Results: Nitazoxanide treatment activated SMAD1/5/8 signaling and increased expression of the downstream target