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

Gene Therapy volume 11, pages 126–132 (2004)Cite this article

Abstract

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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Acknowledgements

This study was supported by Grants-in-Aid for Scientific Research (14657172, 14207036) from the Ministry of Education, Science, and Culture, Tokyo, Japan, by Health Science Research Grants (Comprehensive Research on Aging and Health, and Research on Translational Research) from the Ministry of Health Labor and Welfare, Tokyo, Japan, and by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research, Tokyo, Japan.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    K Ohtani, K Egashira, M Usui, M Ishibashi, K-I Hiasa, Q Zhao & A Takeshita

  2. Division of Gene Therapy Science, Osaka University Medical School, Osaka, Japan

    M Aoki, Y Kaneda & R Morishita

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  1. K Ohtani
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  2. K Egashira
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Ohtani, K., Egashira, K., Usui, M. et al. Inhibition of neointimal hyperplasia after balloon injury by cis-element ‘decoy’ of early growth response gene-1 in hypercholesterolemic rabbits. Gene Ther 11, 126–132 (2004). https://doi.org/10.1038/sj.gt.3302153

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  • DOI: https://doi.org/10.1038/sj.gt.3302153

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