Colchicine Inhibits Smooth Muscle Cell Phenotypic Switch and Aortic Dissection in Mice—Brief Report

BACKGROUND: Aortic dissection (AD) is a severe cardiovascular disorder characterized by intimal tearing and subsequent delamination of the aortic wall. The pathogenesis of AD primarily involves the phenotypic switch of vascular smooth muscle cells (VSMCs), degradation of the extracellular matrix, and chronic vascular inflammation. Colchicine, an alkaloid derived from Colchicum autumnale L , is a Food and Drug Administration–approved anti-inflammatory drug with established therapeutic applications in cardiovascular diseases. However, its potential role in modulating the development or progression of AD remains largely unexplored. METHODS: To investigate the effects of colchicine on AD, a β-aminopropionitrile–induced AD mouse model was used. Colchicine was administered via oral gavage over a 3-week period to evaluate its impact on the incidence and mortality of AD in male C57BL/6J mice. Transcriptome sequencing was performed to identify genes and signaling pathways regulated by colchicine. Additionally, in vitro experiments using primary rat VSMCs were conducted to elucidate the mechanisms underlying colchicine-mediated regulation of VSMC phenotypic switch. RESULTS: Colchicine demonstrated a protective effect against AD by attenuating vascular inflammation and suppressing VSMC phenotypic switch. Mechanistically, colchicine reverses VSMC phenotypic switch at least partially by modulating the expression of myocardin, a key regulator of VSMC contractile phenotype. Transcriptomic analysis further revealed specific genes and pathways influenced by colchicine, providing insights into its molecular mechanisms of action. CONCLUSIONS: This study identifies colchicine as a potential therapeutic drug for AD, highlighting its ability to mitigate hallmark pathological processes such as vascular inflammation and VSMC phenotypic switch. These findings offer a foundation base for the repurposed clinical application of colchicine in AD, which warrants further clinical investigation.