Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, People's Republic of China.
Can J Cardiol. 2012 Nov-Dec;28(6):750-7. doi: 10.1016/j.cjca.2012.01.018. Epub 2012 Jul 17.
Pravastatin can reduce atherosclerotic progression in patients after coronary artery bypass graft. However, it is unknown whether pravastatin has a direct effect on intimal hyperplasia of grafted vessels in vivo or what the underlying mechanisms may be. In this study, a murine vein graft model was applied to deal with these issues.
Vein grafting was performed between C57BL/6J mice. Immediately after operation, pravastatin (30 μM) or phosphate-buffered saline in 50 μL 20% pluronic F-127 gel was delivered to the adventitia of grafted vessels.
Compared with the vehicle, pravastatin significantly reduced intimal hyperplasia 4 weeks after the surgical procedure. Immunohistochemical studies revealed that vascular smooth muscle cells (VSMCs) are a major component of the neointima. The percentage of cells positive for proliferating cell nuclear antigen and Mac-3-positive immunostaining intensity within the intima of vein grafts was significantly lower in the pravastatin-treated group than in the control group. We separated VSMCs from mouse inferior vena cava and collected peritoneal macrophage from mice injected intraperitoneally with 4% thioglycollate. Pravastatin significantly decreased VSMC proliferation and platelet-derived growth factor-induced VSMC migration and, in a dose-dependent manner, inhibited macrophage migration induced by monocyte chemotactic protein-1.
Local delivery of pravastatin at the time of vein-graft surgery directly suppresses subsequent neointimal formation of grafted vessels in a vein graft model of normocholesterolemic mice. These beneficial effects are associated with inhibitory actions on VSMC and macrophage functions.
普伐他汀可降低冠状动脉旁路移植术后患者的动脉粥样硬化进展。然而，尚不清楚普伐他汀是否对体内移植血管的内膜增生有直接作用，其潜在机制可能是什么。在这项研究中，应用了一种小鼠静脉移植模型来解决这些问题。
在 C57BL/6J 小鼠之间进行静脉移植。手术后立即，将普伐他汀（30 μM）或 50 μL 20% pluronic F-127 凝胶中的磷酸盐缓冲盐水施用于移植血管的外膜。
与载体相比，普伐他汀可显著减少术后 4 周的内膜增生。免疫组织化学研究表明血管平滑肌细胞（VSMCs）是新生内膜的主要成分。在普伐他汀治疗组中，内膜中增殖细胞核抗原阳性的细胞百分比和 Mac-3 阳性免疫染色强度明显低于对照组。我们从小鼠下腔静脉分离 VSMCs，并从注射 4%巯基乙醇酸盐的小鼠中收集腹腔巨噬细胞。普伐他汀可显著抑制 VSMC 增殖和血小板衍生生长因子诱导的 VSMC 迁移，并呈剂量依赖性抑制单核细胞趋化蛋白-1诱导的巨噬细胞迁移。
在静脉移植手术时局部给予普伐他汀可直接抑制载脂蛋白正常的小鼠静脉移植模型中移植血管的后续内膜增生。这些有益作用与对 VSMC 和巨噬细胞功能的抑制作用有关。
