CDYL-mediated H3K18 crotonylation upregulates SGK1 to promote vascular smooth muscle cell phenotypic switching

Objective Aortic dissection and aortic aneurysm pose severe threats to patient life and health, with vascular smooth muscle cell (VSMC) phenotypic switching serving as a critical pathological event. Histone modifications have been demonstrated to regulate VSMC phenotypic plasticity. This study aims to investigate the role and underlying mechanism of histone crotonylation in VSMC phenotypic switching.Methods Comprehensive analyses were performed using Western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR), gene knockdown/overexpression, and chromatin immunoprecipitation (ChIP) assays.Results During VSMC phenotypic switching, chromatin-bound protein Y (CDYL) was significantly downregulated, while histone H3 lysine 18 crotonylation (H3K18cr) modification and serum/glucocorticoid-regulated kinase 1 (SGK1) expression were upregulated and negatively regulated by CDYL.Conclusion This study demonstrates that CDYL downregulation promotes H3K18cr-mediated epigenetic activation of SGK1, thereby driving VSMC phenotypic switching. These findings provide novel therapeutic targets and conceptual frameworks for the clinical prevention and treatment of aortic dissection and aneurysm.