Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
PLoS One. 2011;6(10):e26744. doi: 10.1371/journal.pone.0026744. Epub 2011 Oct 28.
Activating transcription factor 3 (ATF3), which is encoded by an adaptive-response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways.
激活转录因子 3（ATF3）是一种由各种刺激诱导的适应性反应基因编码的蛋白，在心血管系统中发挥着重要作用。然而，ATF3 对病理性刺激引起的心肌肥厚的影响尚未确定。在这里，我们使用体外和体内模型研究了 ATF3 缺失对心肌肥厚的影响。通过主动脉缩窄（AB）术诱导小鼠心肌肥厚。通过超声心动图和血流动力学测量以及病理和分子分析来评估心肌肥厚。与野生型（WT）小鼠相比，ATF3 缺失的小鼠在 AB 后 4 周时表现出心肌肥厚、功能障碍和纤维化加剧。此外，与 WT 小鼠相比，ATF3 敲除（KO）小鼠中 MEK-ERK1/2 和 JNK 通路的激活增强。在体外培养的新生小鼠心肌细胞中的研究证实，ATF3 缺失促进了血管紧张素 II 诱导的心肌细胞肥大，这与 MEK-ERK1/2 和 JNK 信号的放大有关。我们的结果表明，ATF3 通过负向调节 MEK-ERK1/2 和 JNK 信号通路，在心肌肥厚的发展中发挥着关键作用。
