A novel role for the plasma membrane calcium pump (PMCA1) in cardiomyopathy and blood pressure control

在英国，大约有100万人受到心力衰竭的影响，患者数量正在迅速上升，患者的存活率与一些癌症相似。众所周知，心力衰竭患者死于两个主要原因，要么是泵衰竭，要么是心跳异常(心律失常)。此外，高血压还会极大地加重心力衰竭。改善心力衰竭的治疗目前非常不令人满意，这是我们研究的主要动机。我们已经证明，一种称为质膜钙泵亚型1(PMCA1)的基因对心力衰竭的所有三个关键特征都是关键的。泵衰竭、心律失常和高血压。PMCA1通过将钙转运出细胞，帮助心肌放松，降低血压。最近对人类的遗传学研究有力地支持了我们的方法，表明PMCA1是人类疾病的关键。我们的计划将把这些调查结果带到下一个基本水平，即了解PMCA1的功能。为此，我们将研究心脏和血管中PMCA1水平已被转基因的小鼠模型。这项计划对了解心力衰竭和高血压至关重要，并将为开发新的治疗方法提供必要的信息。

Heart failure affects around 1 million people in the UK, patient numbers are rising rapidly and survival is similar to that of some cancers. Heart failure patients are known to die from two main causes, either pump failure or heartbeat abnormalities (arrhythmias). In addition, high blood pressure (hypertension) greatly aggravates heart failure. Improving treatment of heart failure, which currently is highly unsatisfactory, is the main motivation for our research. We have shown that a gene called the plasma membrane calcium pump isoform 1 (PMCA1) is central to all three key features of heart failure ? pump failure, arrhythmias and hypertension. By transporting calcium out of the cell PMCA1 helps the heart muscle to relax and blood pressure to fall. Strongly supporting our approach, recent genetic studies in humans have shown that PMCA1 is key to human disease. Our programme will take these findings to the next essential level, i.e. understanding the function of PMCA1. To this end we will study mouse models in which the level of PMCA1 in the heart and vessels has been genetically modified. This programme is pivotal for understanding heart failure and hypertension and will provide information essential to the development of new treatments.