Center for translational Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330002, China.
Department of Physiology and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA19140, USA.
Sci Rep. 2018 May 15;8(1):7595. doi: 10.1038/s41598-018-25874-y.
Restenosis caused by neointimal hyperplasia significantly decreases long-term efficacy of percutaneous transluminal angioplasty (PTA), stenting, and by-pass surgery for managing coronary and peripheral arterial diseases. A major cause of pathological neointima formation is abnormal vascular smooth muscle cell (VSMC) proliferation and migration. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and has reported cardioprotective, neuroprotective and anti-inflammatory effects. However, its role in modulating VSMC neointima formation remains unexplored. Herein, we report that NGR1 inhibits serum-induced VSMC proliferation and migration by regulating VSMC actin cytoskeleton dynamics. Using a mouse femoral artery endothelium denudation model, we further demonstrate that systemic administration of NGR1 had a potent therapeutic effect in mice, significantly reducing neointimal hyperplasia following acute vessel injury. Mechanistically, we show that NGR1's mode of action is through inhibiting the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Taken together, this study identified NGR1 as a potential therapeutic agent for combating restenosis after PTA in cardiovascular diseases.
新生内膜增生引起的再狭窄显著降低了经皮腔内血管成形术（PTA）、支架置入和旁路手术治疗冠状动脉和外周动脉疾病的长期疗效。病理性新生内膜形成的一个主要原因是血管平滑肌细胞（VSMC）的异常增殖和迁移。三七总皂苷 R1（NGR1）是一种从三七中提取的新型皂苷，具有心脏保护、神经保护和抗炎作用。然而，它在调节 VSMC 新生内膜形成中的作用仍未被探索。在此，我们报告 NGR1 通过调节 VSMC 肌动蛋白细胞骨架动力学抑制血清诱导的 VSMC 增殖和迁移。使用小鼠股动脉内皮剥脱模型，我们进一步证明，NGR1 的全身给药在小鼠中具有强大的治疗效果，显著减少急性血管损伤后的新生内膜增生。从机制上讲，我们表明 NGR1 的作用模式是通过抑制磷脂酰肌醇 3-激酶（PI3K）/Akt 信号通路的激活。综上所述，这项研究确定 NGR1 是一种有潜力的治疗药物，可用于对抗心血管疾病 PTA 后的再狭窄。
