DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia?reperfusion in rats - Other RNAi

DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia?reperfusion in rats
July 2006
R. BHINDI, L. M. KHACHIGIAN and H. C. LOWE
Blackwell Synergy
Summary. Background and Aim: The transcription factor and immediate-early gene Egr-1 is widely viewed as a key upstream activator in a variety of settings within cardiovascular pathobiology. The role that Egr-1 plays in myocardial ischemia?reperfusion (IR) injury is unknown. We hypothesized that Egr-1 upregulation is of pathophysiologic importance in myocardial IR injury. Methods and Resources: First, abrogation of Egr-1 mRNA upregulation using Egr-1 targeting DNAzymes in a rat cardiomyocyte in vitro model was demonstrated. Egr-1 mRNA and protein upregulation following myocardial IR in rats were then selectively suppressed by locally delivered DNAzyme. Furthermore, myocardial neutrophil infiltration, intercellular adhesion molecule 1 mRNA and protein expression, and myocardial infarct size were all attenuated in DNAzyme-treated animals. Conclusions: These data support the hypothesis that Egr-1 is a key contributor to myocardial IR injury, and that Egr-1 targeting strategies have therapeutic potential in this context.
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