Myocardial infarction (MI) or heart attack is a deadly event with high prevalence. In the present study, we investigated the effects of the polypeptide copolymer glatiramer acetate (GA) in H9c2 rat cardiomyocytes exposed to oxygen-glucose deprivation/reperfusion injury. Immediately following MI, an acute inflammatory response is triggered that causes activation of various proinflammatory cytokines, infiltration of immune cells, and neovascularization. This response is largely mediated by some genes such as TNF-α, IL-6, ICAM-1, and VEGF. Additionally, the rapid influx of oxidants, such as reactive oxygen species (ROS), leads to a harmful state of oxidative stress. Here, we found that GA could reduce OGD/R-induced inflammation and oxidative stress by inhibiting the expression of TNF-α, IL-6, ICAM-1, and VEGF, and suppressing the production of ROS via reduced NADPH oxidase 1 (NOX1) expression. To elucidate the pathways involved in these promising results, we took a close look at the impact of the endothelial growth response-1 (Egr-1), a transcriptional factor recognized as a mediator of MI-related inflammation and cellular injury. Using siRNA for Egr-1, we found that GA could reduce the expression of ICAM-1 and VEGF by inhibiting Egr-1 expression. Together, our findings indicate a novel therapeutic potential of GA in the treatment of MI.

中文翻译：

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醋酸格拉替雷可通过抑制H9c2细胞中的Egr-1来防止氧葡萄糖剥夺/再灌注引起的损伤。

心肌梗塞（MI）或心脏病发作是高发生率的致命事件。在本研究中，我们调查了多肽共聚物醋酸格拉替雷（GA）在暴露于氧-葡萄糖剥夺/再灌注损伤的H9c2大鼠心肌细胞中的作用。MI后立即引发急性炎症反应，引起各种促炎细胞因子激活，免疫细胞浸润和新血管形成。这种反应很大程度上由某些基因介导，例如TNF-α，IL-6，ICAM-1和VEGF。另外，氧化剂的大量涌入，例如活性氧（ROS），导致氧化应激的有害状态。在这里，我们发现GA可以通过抑制TNF-α，IL-6，ICAM-1和VEGF的表达来减少OGD / R引起的炎症和氧化应激，并通过减少NADPH氧化酶1（NOX1）的表达来抑制ROS的产生。为了阐明涉及这些有希望的结果的途径，我们仔细研究了内皮生长反应-1（Egr-1）的作用，该转录因子被认为是MI相关炎症和细胞损伤的介质。使用针对Egr-1的siRNA，我们发现GA可以通过抑制Egr-1的表达来降低ICAM-1和VEGF的表达。总之，我们的发现表明GA在MI的治疗中具有新的治疗潜力。我们发现GA可以通过抑制Egr-1的表达来降低ICAM-1和VEGF的表达。总之，我们的发现表明GA在MI的治疗中具有新的治疗潜力。我们发现GA可以通过抑制Egr-1的表达来降低ICAM-1和VEGF的表达。总之，我们的发现表明GA在MI的治疗中具有新的治疗潜力。