Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, and the Howard Hughes Medical Institute, Cincinnati, Ohio 45229-3039, USA.
Ann N Y Acad Sci. 2010 Feb;1188:96-102. doi: 10.1111/j.1749-6632.2009.05088.x.
Cardiac hypertrophy results from increased mechanical load on the heart and through the action of neurohumoral mediators. ERK1/2 are known to be activated in response to almost every stress- and agonist-induced hypertrophic stimulus examined to date, suggesting the straightforward hypothesis that these kinases are required for promoting the cardiac growth response. However, recent data from genetically modified mouse models suggest a more complicated picture. For example, inducible expression of dual-specificity phosphatase 6, an ERK1/2-inactivating phosphatase, eliminated ERK1/2 phosphorylation in transgenic mice, but it did not diminish the hypertrophic response to pressure overload. Similarly, Erk1-/- and Erk2+/- mice showed no reduction in stimulus-induced cardiac growth in vivo. However, blockade or deletion of cardiac ERK1/2 did predispose the heart to decompensation and failure after long-term pressure overload. Thus, ERK1/2 signaling is not to be absolutely necessary for mediating cardiac hypertrophy, although it does appear to provide critical protective effects/signals during stress-stimulation.
心肌肥厚是由于心脏受到机械负荷增加和神经体液介质的作用所致。迄今为止，几乎所有研究过的应激和激动剂诱导的心肌肥厚刺激因素都能激活 ERK1/2，这表明这些激酶对于促进心脏生长反应是必需的，这一简单假设是合理的。然而，最近来自基因修饰小鼠模型的研究数据表明，情况更为复杂。例如，双特异性磷酸酶 6 的诱导表达，一种 ERK1/2 失活磷酸酶，消除了转基因小鼠中 ERK1/2 的磷酸化，但并未减少压力超负荷引起的心肌肥厚反应。同样，Erk1-/-和 Erk2+/-小鼠在体内刺激诱导的心肌生长没有减少。然而，心脏 ERK1/2 的阻断或缺失会使心脏在长期压力超负荷后更容易失代偿和衰竭。因此，ERK1/2 信号传导对于介导心肌肥厚并非绝对必要，尽管它在应激刺激期间确实提供了关键的保护作用/信号。
