RESUMO
The present study investigated the effects of formononetin (FMN) against balloon injuryinduced neointima formation in vivo and plateletderived growth factor (PDGF)BBinduced proliferation and migration of vascular smooth muscle cells (VSMCs) in vitro, and explored the underlying mechanisms. A rat model of carotid artery injury was established, in order to examine the effects of FMN on balloon injuryinduced neointima formation. Histological observation of the carotid artery tissues was conducted by hematoxylin and eosin staining. VSMC proliferation during neointima formation was observed by proliferating cell nuclear antigen staining. Subsequently, rat aortic VSMCs were isolated, and the effects of FMN on PDGFBBinduced VSMC proliferation and migration were determined using Cell Counting Kit8 and Transwell/wound healing assays, respectively. Immunohistochemical and immunocytochemical staining was applied to measure the expression of transforming growth factor (TGF)ß in carotid artery tissues and VSMCs, respectively. SMAD family member 3 (Smad3)/phosphorylated (p)Smad3 expression was examined by western blotting. FMN treatment significantly inhibited the abnormal proliferation of smooth muscle cells in neointima, and alterations to the vascular structure were attenuated. In addition, pretreatment with FMN effectively inhibited the proliferation of PDGFBBstimulated VSMCs (P<0.05). FMN also reduced the number of cells that migrated to the lower surface of the Transwell chamber and decreased woundhealing percentage (P<0.05). The expression levels of TGFß were decreased by FMN treatment in vivo and in vitro, and Smad3/pSmad3 expression was also markedly inhibited. In conclusion, FMN significantly protected against balloon injuryinduced neointima formation in the carotid artery of a rat model; this effect may be associated with the regulation of VSMC proliferation and migration through altered TGFß1/Smad3 signaling.