Myocardial hypertrophy, an inflammatory condition of cardiac muscles is a maladaptive response of the heart to biomechanical stress, hemodynamic or neurohormonal stimuli. Previous studies indicated that knockout of Arginyltransferase (ATE1) gene in mice and embryos leads to contractile dysfunction, defective cardiovascular development, and impaired angiogenesis. Here we found that in adult rat model, downregulation of ATE1 mitigates cardiac hypertrophic, cardiac fibrosis as well as apoptosis responses in the presence of cardiac stress i.e. renal artery ligation. On contrary, in wild type cells responding to renal artery ligation, there is an increase of cellular ATE1 protein level. Further, we have shown the cardioprotective role of ATE1 silencing is mediated by the interruption of TAK1 activity-dependent JNK1/2 signaling pathway. We propose that ATE1 knockdown in presence of cardiac stress performs a cardioprotective action and the inhibition of its activity may provide a novel approach for the treatment of cardiac hypertrophy.

中文翻译：

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精氨酸转移酶敲低可通过TAK1-JNK1 / 2途径减轻心脏肥大和纤维化。

心肌肥大是心肌炎性反应，是心脏对生物力学应力，血液动力学或神经激素刺激的适应不良反应。先前的研究表明，敲除小鼠和胚胎中的精氨酸转移酶（ATE1）基因会导致收缩功能障碍，心血管发育不良和血管生成受损。在这里，我们发现在成年大鼠模型中，ATE1的下调可减轻心脏肥大，心脏纤维化以及存在心脏应激（即肾动脉结扎）时的细胞凋亡反应。相反，在响应肾动脉结扎的野生型细胞中，细胞ATE1蛋白水平增加。此外，我们已经表明，ATE1沉默的心脏保护作用是由TAK1活性依赖性JNK1 / 2信号传导途径的中断介导的。