Bhindi R, Khachigian L M, Lowe H C
Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
J Thromb Haemost. 2006 Jul;4(7):1479-83. doi: 10.1111/j.1538-7836.2006.02022.x.
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.
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.
转录因子及即早基因Egr-1在心血管病理生物学的多种情况下被广泛视为关键的上游激活因子。Egr-1在心肌缺血再灌注（IR）损伤中所起的作用尚不清楚。我们推测Egr-1的上调在心肌IR损伤中具有病理生理重要性。
首先，在大鼠心肌细胞体外模型中证实了使用靶向Egr-1的脱氧核酶消除Egr-1 mRNA上调。然后，通过局部递送脱氧核酶选择性抑制大鼠心肌IR后Egr-1 mRNA和蛋白的上调。此外，在脱氧核酶处理的动物中，心肌中性粒细胞浸润、细胞间黏附分子1 mRNA和蛋白表达以及心肌梗死面积均减小。
这些数据支持以下假设，即Egr-1是心肌IR损伤的关键促成因素，并且在这种情况下靶向Egr-1的策略具有治疗潜力。
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