Taken together, our results demonstrate that HFD+CKD upregulates ROS regulator gene expressions in the aorta via a CASP4/11-dependent manner and that LPS transfection induced mitoROS, inhibition of mitoROS decreased CASP4 activation, N-GSDMD membrane expression, and VCAM-1 upregulation, suggesting that mitoROS are functional upstream of CASP4/11 activation. This evidence concerns the gene CASP4 and chronic kidney disease.