The sarcolemmal calcium signalling protein PMCA4 as a novel target to reduce cardiac hypertrophy and failure

心力衰竭仅在英国就影响了近100万人。心力衰竭是一种心脏无法再为身体组织提供足够血液以满足其代谢需求的疾病。尽管最近在治疗这种疾病方面取得了进展，但预后仍然很差，2-5%的人口可能死于心力衰竭。因此，我们必须了解这种情况是如何以及为什么发展的，以便制定更好的治疗策略。心力衰竭是在心脏受到诸如高血压或心脏病发作等损害后发展的，这将导致心肌增大，称为肥大，由于MRC先前的资助，我们已经确定，通过删除质膜钙泵（PMCA 4），从小鼠模型的心脏细胞中提取的基因，我们可以保护心脏免于肥大（肌肉增大）在拟议的工作计划中，我们的目标是确定PMCA 4的缺失如何以及为什么保护心脏免受肥大，心衰我们还将确定该基因是否参与心力衰竭患者的疾病发展。在未来，有可能用一种药物来治疗心力衰竭患者，以阻止PMCA 4蛋白的作用，从而保护这些患者免受心力衰竭的影响;在这个项目中，我们将采取第一步来确定一种具有这种预期效果的物质。

Heart failure affects nearly 1 million people in the UK alone. Heart failure is a condition in which the heart can no longer supply the tissues of the body with enough blood to meet its metabolic demands. Despite recent progress in the treatment of this condition prognosis remains very poor, with 2-5% of the population likely to die from heart failure. It is therefore essential that we understand how and why this condition develops in order to develop better treatment strategies. Heart failure develops following an insult to the heart such as high blood pressure or a heart attack, this will lead to enlargement of the heart muscle, known as hypertrophy, before progressing to heart failure.As a result of previous funding from the MRC we have determined that by deleting the plasma membrane calcium pump (PMCA4) gene from the cells of the heart in a mouse model that we can protect the heart from developing hypertrophy (muscle enlargement) and ultimately heart failure.In the proposed programme of work we aim to determine how and why deletion of PMCA4 protects the heart from hypertrophy and heart failure. We will also determine whether this gene is involved in the development of disease in heart failure patients. In the future it may be possible to treat heart failure patients with a drug to stop the action of the PMCA4 protein and therefore protect these patients from heart failure; in this project we will take the first steps to identify a substance which would have this desired effect.