DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia-reperfusion in rats.
OBJECTIVE
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.
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.
Bhindi
R
R
Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Khachigian
L M
LM
Lowe
H C
HC
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D021881:DNA, Catalytic / Q000008:administration & dosage / Q000627:therapeutic use*; D051766:Early Growth Response Protein 1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000473:pathology; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D021881:DNA, Catalytic; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1