PIEZO1 and Hyperglycemia: After 6 months of hyperglycemia, HE staining showed a larger de-endothelialized region and thickened tunica media in the aortic endothelium of Piezo1flox/flox mice (Fig. 1I), accompanied by vacuolization of the vascular smooth muscle, indicating that Piezo1 activation could aggravate irreversible endothelial damage in prolonged hyperglycemia.