Collectively, we identified the key signaling pathways and hub genes (CD74, COL1A1, TXNRD1, CCND1, COL5A1, SERPINH1, BCL6, ITGA10, FOS, and JUNB) in AS and AI pathological processes, which may become the potential indicative biomarkers or important regulatory targets in AS and AI pathogenesis. This evidence concerns the gene SERPINH1 and aortic stenosis.