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Local Delivery of Pravastatin Inhibits Intimal Formation in a Mouse Vein Graft Model.
MedLine Citation:
PMID:  22809888     Owner:  NLM     Status:  Publisher    
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.
Li Zhang; Heng Jin; Jianfei Huang; Huihe Lu; Yunyuan Guan; Xiaolan Chen; Hua Sun
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-16
Journal Detail:
Title:  The Canadian journal of cardiology     Volume:  -     ISSN:  1916-7075     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8510280     Medline TA:  Can J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, People's Republic of China.
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