Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
Institute of Biology, National Engineering and Research Center for Natural Medicines, Chinese Academy of Sciences, Chengdu, People's Republic of China.
Eur J Pharmacol. 2019 Jul 5;854:213-223. doi: 10.1016/j.ejphar.2019.03.050. Epub 2019 Mar 30.
Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events in the pathological course of atherosclerosis and restenosis after percutaneous coronary intervention (PCI). Dioscin has been shown to exhibit powerful cardiovascular protective effects and potent therapeutic potential in cancer owing to the inhibition of cell proliferation and migration. However, its effects on arterial wall hypertrophy-related diseases caused by VSMC proliferation and migration remain unclear. In this study, we investigated the effects of dioscin on intimal hyperplasia after balloon injury in vivo, its effects on VSMC proliferation and migration in vitro, and the mechanisms underlying these effects. Results showed that dioscin treatment significantly inhibited VSMC proliferation and intimal thickening after balloon injury. In cultured VSMCs, treatment with dioscin significantly decreased fetal bovine serum or platelet-derived growth factor-induced cell proliferation and migration. Moreover, dioscin inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and expression of Forkhead box M1 (FoxM1) and its downstream target genes. FoxM1 knockdown with shRNA partially counteracted the inhibitory effects of dioscin on cell proliferation and migration. In conclusion, we demonstrated that dioscin attenuated neointima formation in response to balloon injury by suppressing VSMC proliferation and migration through MAPK-FoxM1 pathway. Our data suggested that dioscin might be a potential therapeutic agent for atherosclerosis and restenosis after PCI.
血管平滑肌细胞 (VSMC) 增殖和迁移是动脉粥样硬化病理过程和经皮冠状动脉介入治疗 (PCI) 后再狭窄的关键事件。薯蓣皂苷已被证明由于抑制细胞增殖和迁移，在癌症中具有强大的心血管保护作用和潜在的治疗潜力。然而，其对由 VSMC 增殖和迁移引起的动脉壁肥厚相关疾病的影响尚不清楚。在本研究中，我们研究了薯蓣皂苷在体内球囊损伤后内膜增生中的作用、在体外对 VSMC 增殖和迁移的作用及其作用机制。结果表明，薯蓣皂苷治疗可显著抑制球囊损伤后 VSMC 增殖和内膜增厚。在培养的 VSMCs 中，薯蓣皂苷处理显著降低了胎牛血清或血小板衍生生长因子诱导的细胞增殖和迁移。此外，薯蓣皂苷抑制细胞外信号调节激酶 1/2 (ERK1/2) 的磷酸化和叉头框 M1 (FoxM1) 的表达及其下游靶基因。FoxM1 的 shRNA 敲低部分抵消了薯蓣皂苷对细胞增殖和迁移的抑制作用。总之，我们证明薯蓣皂苷通过 MAPK-FoxM1 通路抑制 VSMC 增殖和迁移来减轻球囊损伤后的新生内膜形成。我们的数据表明，薯蓣皂苷可能是 PCI 后动脉粥样硬化和再狭窄的潜在治疗剂。
