Showing papers by "Colin N. Chesterman published in 2002"

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

Abstract: 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.