Basic Research Local Delivery of Pravastatin Inhibits Intimal Formation in a Mouse Vein Graft Model

Background: 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. Methods: Vein grafting was performed between C57BL/6J mice. Immediately after operation, pravastatin (30 M) or phosphate-buffered saline in 50 L 20% pluronic F-127 gel was delivered to the adventitia of grafted vessels. Results: 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.