S-(-)-equol alleviates stenosis of the injured carotid artery in Sprague Dawley rats by preventing the vascular smooth muscle cell phenotypic switch via inhibition of the MAPK(p38)-NF kappa B-p65 signaling

Phenotypic switching of the vascular smooth muscle cells (VSMCs) is closely related to an in-stent restenosis (ISR). This study aimed to investigate whether S-(-)-equol prevented the phenotypic switch of the VSMCs as a potential treatment of an ISR. The carotid arteries of female Sprague Dawley (SD) rats with or without a carotid injury and ovariectomy were harvested after 4 weeks of treatment with S-(-)-equol. Stenosis of the carotid artery and two phenotype-related proteins-alpha smooth muscle actin (alpha SMA) and osteopontin (OPN)-were determined. The proliferation and migration capacities of VSMCs were determined by the CCK-8 and transwell assays, respectively. The expressions of alpha SMA, OPN, MAPK(p38), p-MAPK(p38), NF-kappa B-p85, and p-NF-kappa B-p88 were detected by a western blot. S-(-)-equol alleviated carotid stenosis and prevented the VSMC phenotypic switch in female SD rats with a carotid artery injury and a bilateral ovariectomy. S-(-)-equol inhibited the phenotypic switch of VSMCs, which was induced by PDGF-BB, and enhanced the proliferation and migration of VSMCs. The effects of S-(-)-equol on VSMCs were confirmed to be related to the inactivation of the GPER-MAPK(p38)-NF-kappa B-p88 signaling in vitro and in vivo. Our results indicate that S-(-)-equol affects carotid stenosis by preventing the phenotypic switch of VSMCs via the GPER-MAPK(p38)-NF-kappa B-p88 signaling pathway.