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

被引：45

作者：

Bhindi, R.

Khachigian, L. M.

Lowe, H. C. ^{[1
]}

机构：

[1] Univ New S Wales, Ctr Vasc Res, Sch Med Sci, Sydney, NSW 2052, Australia

[2] Univ Sydney, Fac Med, Concord Repatriat Gen Hosp, Dept Cardiol, Sydney, NSW 2006, Australia

来源：

JOURNAL OF THROMBOSIS AND HAEMOSTASIS | 2006年 / 4卷 / 07期

关键词：

Egr-1; gene targeting; ICAM-1; ischemia-reperfusion; myocardial;

D O I：

10.1111/j.1538-7836.2006.02022.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 I 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.

引用

页码：1479 / 1483

页数：5

共 20 条

[1] Helicobacter pylori activates the early growth response 1 protein in gastric epithelial cells [J].