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 μM) or phosphate-buffered saline in 50 μL 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.


CONCLUSIONS
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.
Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, People's Republic of China.
Li
L
Zhang
Heng
H
Jin
Jianfei
J
Huang
Huihe
H
Lu
Yunyuan
Y
Guan
Xiaolan
X
Chen
Hua
H
Sun
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D017035:Pravastatin / Q000008:administration & dosage*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*; D014680:Veins / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin