Compared with the HC-vitD2 group, oral administration of Gbz for 18 weeks significantly increased ATF4 and Nox4 levels, reduced CHOP expression, mitigated calcium deposition as shown by Alizarin Red and OsteoSense staining, alleviated aortic stenosis as evidenced by decreased transvalvular peak and mean pressure gradient on echocardiography, and mitigated cardiac dysfunction. Here, NOX4 is linked to aortic stenosis.