Integrative Physiology of the Plasma Membrane Calcium Pump Isoform 4 in the Healthy and Failing Heart

心力衰竭是指心脏不能向全身输送足够的血液，它的早期症状是导致残疾的主要原因，降低了我们老龄化人口的生活质量和死亡。为了开发更好的治疗方法，我们必须增加对导致心力衰竭的基因和分子变化的了解。钙对心脏的正常功能非常重要，众所周知，钙水平的破坏会导致心血管并发症。参与钙从心脏细胞中移动的蛋白质之一是质膜钙泵（PMCA）；在这个项目中，我们的目标是找出PMCA如何调节心脏的工作。具体来说，我们将产生PMCA表达修饰的小鼠，并确定这是否会导致心脏结构和/或功能的变化。我们使用老鼠作为模型系统，因为它反映了人类的心脏，我们能够使用类似于临床医生使用的工具来确定心脏的工作情况。这项研究将提高我们对心力衰竭的理解，并可能导致潜在的新治疗策略。

Heart failure, which is a condition in which the heart is unable to pump sufficient blood throughout the body, and its early signs are a major cause of disability, reduced quality of life and death in our aging population. In order to develop better treatments we must increase our understanding of the genetic and molecular changes which lead to heart failure. Calcium is very important for the correct functioning of the heart and it is well know that disruption of calcium levels leads to cardiovascular complications. One of the proteins involved in the movement of calcium from heart cells is the plasma membrane calcium pump (PMCA); in this project we aim to find out how PMCA regulates the working of the heart. Specifically we will generate mice with modified expression of PMCA and determine whether this leads to changes in the structure and/or function of the heart. We use the mouse as a model system as it reflects the human heart and we are able to use tools similar to those used by clinicians to determine how well the heart is working.This research will improve our understanding of heart failure and may lead to potential new treatment strategies.