PIEZO1 mediates a mechanothrombotic pathway in diabetes
Wandi Zhu, Shihui Guo, Max Homilius, Cissy Nsubuga, Shane H. Wright, Dajun Quan, Ashmita KC, Samuel S. Eddy, Rachelle A. Victorio, Manu Beerens, Robert Flaumenhaft, Rahul C. Deo, Calum A. MacRae
Abstract
transcription in mature blood cells and selected high Piezo1–expressing hematopoietic stem cell clones. Elevated Piezo1 activity in platelets, red blood cells, and neutrophils in T2DM triggered discrete prothrombotic cellular responses. Inhibition of Piezo1 protected against thrombosis both in human blood and in zebrafish genetic models, particularly in hyperglycemia. Our findings identify a candidate target to precisely modulate mechanically induced thrombosis in T2DM and a potential screening method to predict patient-specific risk. Ongoing remodeling of cell lineages in hematopoiesis is an integral component of thrombotic risk in T2DM, and related mechanisms may have a broader role in chronic disease.