Wang Dong, Wang Qingjie, Yan Gaoliang, Qiao Yong, Tang Chengchun
Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Nanjing, China.
J Cardiovasc Pharmacol. 2015 May;65(5):444-55. doi: 10.1097/FJC.0000000000000213.
Abnormal vascular smooth muscle cell proliferation and migration are key factors in many cardiovascular diseases. Here, we investigated the effects of phloretin on platelet-derived growth factor homodimer (PDGF-BB)-induced rat aortic smooth muscle cell (RASMC) proliferation, migration, and neointimal formation after carotid injury. Phloretin significantly inhibited the PDGF-BB-stimulated RASMC proliferation in a concentration-dependent manner (10-100 μM). Also, PDGF-BB-stimulated RASMC migration was inhibited by phloretin at 50 μM. Pretreating RASMC with phloretin dose-dependently inhibited PDGF-BB-induced Akt and p38 mitogen-activated protein kinases activation. Furthermore, phloretin increased p27 and decreased cyclin-dependent kinase 2, CDK4 expression, and p-Rb activation in PDGF-BB-stimulated RASMC in a concentration-dependent manner (10-50 μM). PDGF-BB-induced cell adhesion molecules and matrix metalloproteinase-9 expression were blocked by phloretin at 50 μM. Preincubation with phloretin dose-dependently reduced the intracellular reactive oxygen species production. In vivo study showed that phloretin (20 mg/kg) significantly reduced neointimal formation 14 days after carotid injury in rats. Thus, phloretin may have potential as a treatment against atherosclerosis and restenosis after vascular injury.
血管平滑肌细胞异常增殖和迁移是多种心血管疾病的关键因素。在此，我们研究了根皮素对血小板衍生生长因子同二聚体（PDGF-BB）诱导的大鼠主动脉平滑肌细胞（RASMC）增殖、迁移以及颈动脉损伤后新生内膜形成的影响。根皮素以浓度依赖性方式（10 - 100 μM）显著抑制PDGF-BB刺激的RASMC增殖。此外，50 μM的根皮素可抑制PDGF-BB刺激的RASMC迁移。用根皮素预处理RASMC可剂量依赖性地抑制PDGF-BB诱导的Akt和p38丝裂原活化蛋白激酶激活。此外，根皮素以浓度依赖性方式（10 - 50 μM）增加PDGF-BB刺激的RASMC中p27的表达，降低细胞周期蛋白依赖性激酶2（CDK4）的表达以及p-Rb的激活。50 μM的根皮素可阻断PDGF-BB诱导的细胞黏附分子和基质金属蛋白酶-9的表达。用根皮素预孵育可剂量依赖性地减少细胞内活性氧的产生。体内研究表明，根皮素（20 mg/kg）可显著减少大鼠颈动脉损伤14天后的新生内膜形成。因此，根皮素可能具有治疗动脉粥样硬化和血管损伤后再狭窄的潜力。
