Document Detail


Ginkgolide A-gold nanoparticles inhibit vascular smooth muscle proliferation and migration in vitro and reduce neointimal hyperplasia in a mouse model.
MedLine Citation:
PMID:  21571322     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Neointimal formation is mediated by phenotypic changes in vascular smooth muscle cells (SMC) and is an important mediator of restenosis following arterial reconstruction. We conjugated antioxidant ginkgolide A (GA) to gold nanoparticles (GNP) to determine the effect of GA delivery on neointimal formation.
MATERIALS AND METHODS: GA was conjugated to 80 nm GNP in an overnight incubation. Mouse P53LMAC01 vascular SMC were treated with various doses of GA-GNP, GA alone, GNP alone, and no treatment control. Cell proliferation and migration were analyzed, and superoxide anion levels and the phosphorylation status of ERK1/2 were determined. Mice underwent ligation of the common carotid artery along with local treatment with GNP (control) or GA-GNP. The carotid artery was harvested and subjected to immunohistochemical analysis.
RESULTS: GA-GNP treatment significantly inhibited SMC proliferation and migration in vitro in comparison to GNP treatment alone, and the effect persisted for up to 72 h after treatment. Treatment with GA-GNP also reduced superoxide anion levels in vitro. PDGF-BB substantially induced ERK1/2 phosphorylation in GNP control cells; this PDGE-BB induced ERK1/2 phosphorylation was significantly inhibited in GA-GNP-treated cells compared with GNP only. GA-GNP significantly reduced neointimal hyperplasia after injury in mice, and proliferating cell nuclear antigen (PCNA) staining was reduced substantially in the arteries of mice treated with GA-GNP.
CONCLUSIONS: GA-GNP reduce vascular SMC proliferation and migration in vitro through reduced activation of ERK1/2. Local treatment with GA-GNP in areas of arterial injury reduced neointimal hyperplasia and subsequent stenosis.
Authors:
Sarah M Weakley; Xinwen Wang; Hong Mu; Jianming Lü; Peter H Lin; Qizhi Yao; Changyi Chen
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-04-01
Journal Detail:
Title:  The Journal of surgical research     Volume:  171     ISSN:  1095-8673     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-17     Completed Date:  2012-01-09     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division / drug effects
Cell Line
Cell Movement / drug effects
Disease Models, Animal
Ginkgolides / pharmacology*
Gold / pharmacology*
Hyperplasia / drug therapy
Lactones / pharmacology*
Metal Nanoparticles / therapeutic use*
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Muscle, Smooth, Vascular / pathology*
Myocytes, Smooth Muscle / drug effects*,  pathology
Neointima / drug therapy*,  pathology
Platelet-Derived Growth Factor / pharmacology
Superoxides / antagonists & inhibitors
Grant Support
ID/Acronym/Agency:
T32 HL083774/HL/NHLBI NIH HHS; T32 HL083774-03/HL/NHLBI NIH HHS; T32 HL083774-04/HL/NHLBI NIH HHS; T32HL083774/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ginkgolides; 0/Lactones; 0/Platelet-Derived Growth Factor; 0/ginkgolide A; 11062-77-4/Superoxides; 7440-57-5/Gold; EC 2.7.11.24/Mapk1 protein, mouse; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3
Comments/Corrections

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