Persistent cardiac hypertrophy eventually leads to deterioration of heart function and changes to normal morphology. Decreased nitric oxide (NO) production plays a critical role in modulating cardiac hypertrophy. Interleukin enhancement binding factor 3 (ILF3), a member of the double-stranded RNA-binding protein family, is known to regulate the transcription and stability of mRNA. Therefore, the major aim of the present study was to determine the role of ILF3 in reduction of NO production in cardiac hypertrophy. Cardiac hypertrophy models of neonatal rat cardiomyocytes (NRCMs) and adult rats were induced by angiotensin II (Ang II) in this study. First, it was found that ILF3 expression, NO production, and nitric oxide synthase (NOS) activity was decreased in cultured cardiomyocytes and adult rats treated with Ang II, compared with NRCMs treated with vehicle and rats treated with saline infusion, respectively. These effects induced by Ang II were significantly exacerbated by specific ILF3 knockdown. Moreover, the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, was increased significantly in the Ang II-induced hypertrophic NRCMs and adult rats. Additionally, decreased protein expression and mRNA level of dimethylarginine dimethylaminohydrolases 1 (DDAH1, which degrades ADMA) were observed. Furthermore, specific ILF3 knockdown further aggravated these effects, but didn't reduce the expression level of NOS isoforms. In conclusion, our data show that ADMA accumulation-mediated decrease in NO production plays an important role in cardiomyocyte remodeling, which may be associated with ILF3-mediated DDAH1 reduction.

中文翻译：

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白介素增强结合因子3通过靶向不对称二甲基精氨酸一氧化氮抑制心脏肥大。

持续性心肌肥大最终会导致心脏功能恶化并改变为正常形态。一氧化氮（NO）产量减少在调节心脏肥大中起关键作用。白介素增强结合因子3（ILF3），双链RNA结合蛋白家族的成员，已知调节mRNA的转录和稳定性。因此，本研究的主要目的是确定ILF3在减少心肌肥大中NO生成中的作用。在这项研究中，血管紧张素II（Ang II）诱导了新生大鼠心肌细胞（NRCM）和成年大鼠的心脏肥大模型。首先，我们发现培养的心肌细胞和接受Ang II处理的成年大鼠中ILF3表达，NO生成和一氧化氮合酶（NOS）活性降低，与分别用赋形剂治疗的NRCM和用盐水输注的大鼠进行比较。特异性ILF3敲低显着加剧了Ang II诱导的这些作用。此外，在Ang II诱导的肥大性NRCM和成年大鼠中，NOS的内源性抑制剂非对称二甲基精氨酸（ADMA）的水平显着增加。此外，观察到二甲基精氨酸二甲基氨基水解酶1（DDAH1，降解ADMA）的蛋白质表达和mRNA水平降低。此外，特异性的ILF3敲低进一步加重了这些影响，但并未降低NOS亚型的表达水平。总之，我们的数据表明，ADMA积累介导的NO生成减少在心肌细胞重构中起重要作用，这可能与ILF3介导的DDAH1减少有关。