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Thromb Haemost 2002; 87(01): 134-140
DOI: 10.1055/s-0037-1612956
Review Article
Schattauer GmbH

Catalytic Antisense DNA Molecules Targeting Egr-1 Inhibit Neointima Formation following Permanent Ligation of Rat Common Carotid Arteries

Harry C. Lowe
1   Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia
,
Colin N. Chesterman
1   Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia
,
Levon M. Khachigian
1   Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia
› Institutsangaben
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Publikationsverlauf

Received 23. Juli 2001

Accepted after revision 10. September 2001

Publikationsdatum:
13. Dezember 2017 (online)

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Summary

Animal models of neointima (NI) formation have proven useful in gaining insights into the mechanisms of restenosis after coronary angioplasty and stenting, but the events at a molecular level remain incompletely understood. Here, we describe a technically straightforward, rat model of NI formation, involving complete ligation of the common carotid artery and demonstrate the importance of the immediate-early gene and zinc finger transcription factor Egr-1 in this process. Acute cessation of common carotid blood flow by vessel ligation, was followed by the expression of Egr-1 in the arterial media within 3 h and NI formation proximal to the point of ligation at 18 days. Local delivery of catalytic oligodeoxynucleotides (ODN) targeting rat Egr-1 mRNA at the time of ligation reduced both Egr-1 expression and NI formation in this model. In contrast, a scrambled version of this ODN had no inhibitory effect. These studies demonstrate for the first time that arterial intimal thickening following artery ligation is critically-dependent on the activation of Egr-1.

Keywords

Neointima - Egr-1 - oligonucleotide
 

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