DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia-reperfusion in rats
DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia-reperfusion in rats
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DOI：
10.1111/j.1538-7836.2006.02022.x
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发表时间：
2006-07-01
影响因子：
10.4
通讯作者：
Lowe, H. C.
中科院分区：
文献类型：
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作者：
Bhindi, R.;Khachigian, L. M.;Lowe, H. C.
背景和目的：转录因子和即早基因 Egr-1 被广泛视为心血管病理学中多种环境中的关键上游激活剂。 Egr-1 在心肌缺血再灌注 (IR) 损伤中的作用尚不清楚。我们假设 Egr-1 上调在心肌 IR 损伤中具有重要的病理生理学意义。方法和资源：首先，在大鼠心肌细胞体外模型中证明了使用 Egr-1 靶向 DNAzyme 可以消除 Egr-1 mRNA 上调。大鼠心肌 IR 后 Egr-1 mRNA 和蛋白质的上调被局部递送的 DNAzyme 选择性抑制。此外，在 DNAzyme 处理的动物中，心肌中性粒细胞浸润、细胞间粘附分子 I mRNA 和蛋白质表达以及心肌梗塞面积均减弱。结论：这些数据支持这样的假设：Egr-1 是心肌 IR 损伤的关键因素，并且 Egr-1 靶向策略在此背景下具有治疗潜力。
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.