Taken together, our results demonstrate that HFD+CKD upregulate the expression of 998 genes with upregulation of 5 TI genes, including IL1B, NLRP3, CLEC7A, mTOR, and NOS2, in the aorta; IL1B not only serves as a cytokine readout for CASP4/11 activation and the N-GSDMD protein pore-secretome but also acts as the second step for HFD+CKD-promoted TI to accelerate vascular inflammation. The gene discussed is NOS2; the disease is chronic kidney disease.