The role of ERK MAPKs in compensated cardiac hypertrophy

根据最近的统计数据，澳大利亚每年有近300人死于心力衰竭。事实上，尽管其他形式的心脏和血管疾病的发病率有所下降，但心力衰竭现在是一个正在上升的主要健康问题。我们现在的情况是，治疗心力衰竭的费用超过了治疗所有癌症患者的费用，而且患有心力衰竭的患者住院的天数比任何其他心脏或血管疾病的患者都要多。大多数情况下，心脏在长期暴露于高血压后不能作为一个有效的泵。施加在心脏上的增加的工作负荷有效地迫使它在一个称为心脏肥厚的过程中增大体积。但这种对病人有益的初始补偿通常会恶化，许多心脏细胞会死亡。由此导致的心脏细胞死亡就是心脏的衰竭，病人的死亡是不可避免的。伴随心肌肥大和心力衰竭的心脏细胞功能蛋白分子的根本变化可能是极其复杂的。到目前为止，还没有一项研究对这种复杂性进行了全面而公正的研究。然而，有新技术可以让我们看到这样的景象。我们已经建立了一个合作研究小组来研究心脏肥厚的基本机制。我们正在开发一种新的模型，在这种模型中，肥大不会进展到失败。我们的综合专业知识使我们能够使用最新开发的科学方法来评估这些心脏事件的生化基础。我们选择重点记录伴随心肌肥厚的蛋白质变化，目的是建立重要的干预靶点，使心肌细胞在肥厚的情况下存活。这将对预防心力衰竭具有重要意义。

According to recent statistics, heart failure accounts for almost 300 deaths each year in Australia. In fact, heart failure is now a major health problem that is on the rise, despite the reduced incidence of other forms of heart and blood vessel disease. We are now in the situation where the cost of treatment of heart failure exceeds that of treating all cancer patients, and there are more patient days in hospital with heart failure than with any other heart or blood vessel disease. Most often, the heart fails to act as an effective pump following long-term exposure to high blood pressure. The increased work load placed on the heart effectively forces it to increase in size in a process called cardiac hypertrophy. But this initial compensation which is of benefit to the patient commonly deteriorates and many of the heart cells die. The resulting death of heart cells is the failure of the heart, and death of the patient is inevitable. The fundamental changes in the functional protein molecules of the heart cells that accompany hypertrophy and heart failure are likely to be extremely complex. As yet, no research has taken a global and unbiased look into this complexity. However, there are new technologies that allow us to take such a look. We have established a collaborative research team to investigate the fundamental mechanisms underlying cardiac hypertrophy. We are exploiting a novel model in which hypertrophy does not progress to failure. Our combined expertise allows us to use recently developed scientific methodologies to evaluate the biochemical basis for these events in the heart. We have chosen to focus on documenting the changes in proteins that accompany cardiac hypertrophy with the aim to establish important targets for interventions to permit cardiac cells to survive despite hypertrophy. This will have important implications for preventing cardiac failure.