The deubiquitinase USP17 was previously shown to regulate KLF4 expression in hepatocellular carcinomas. The KLF4 transcription factor is a major regulator of the phenotypic response of vascular smooth muscle cells, enabling their polarization toward a synthetic phenotype observed in several aortic remodeling diseases, including aneurysms and atherosclerosis. The aim here was therefore to reduce USP17 expression in primary-cultured human aortic smooth muscle cells and to verify their fate (contractile or synthetic phenotype) through proteomic analysis.