Inhibition of neointimal hyperplasia after balloon injury by cis-element ‘decoy’ of early growth response gene-1 in hypercholesterolemic rabbits

被引：0
作者：
K Ohtani
K Egashira
M Usui
M Ishibashi
K-I Hiasa
Q Zhao
M Aoki
Y Kaneda
R Morishita
A Takeshita
机构：
[1] Graduate School of Medical Sciences,Department of Cardiovascular Medicine
[2] Kyushu University,Division of Gene Therapy Science
[3] Osaka University Medical School,undefined
来源：
Gene Therapy | 2004年 / 11卷
关键词：
neointimal hyperplasia; inflammation; growth factor;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Early growth response factor-1 (Egr-1) is a transcription factor that is rapidly activated after vascular injury and thus might contribute to vascular proliferation and inflammation. We hypothesized that Egr-1 might therefore be a therapeutic target against restenosis. Hypercholesterolemic rabbits were intraluminally administered synthetic DNA as a ‘decoy’ against Egr-1 immediately after carotid artery balloon injury. Efficient transfection was confirmed by the delivery of a fluorescence-labeled decoy. Gel mobility-shift assay showed increased Egr-1 activity after balloon injury and its prevention by Egr-1 decoy transfection in vivo. Egr-1 decoy transfection attenuated early inflammation and proliferation and later neointimal hyperplasia. In addition, Egr-1 decoy transfection reduced gene expression and protein production of Egr-1-dependent genes such as platelet-derived growth factor-B, transforming growth factor-β1, and monocyte chemoattractant protein-1. The Egr-1 pathway has an essential role in the pathogenesis of neointimal hyperplasia after balloon injury in hypercholesterolemic rabbits. This decoy strategy is a potential practical form of therapy for human restenosis.
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页码：126 / 132
页数：6
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