Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty‐induced neointimal hyperplasia

Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell‐cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound‐healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty‐induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell‐cycle arrest at the G0/G1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3‐kinase, v‐akt murine thymoma viral oncogene homolog 1, and extracellular signal‐regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase‐2 and matrix metalloproteinase‐9. In vivo data indicated that ugonin J prevented balloon angioplasty‐induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury‐induced neointimal formation.

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