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

肌膜钙信号蛋白 PMCA4 作为减少心脏肥大和衰竭的新靶点

• 批准号: G0802004/1
• 负责人: Ludwig Neyses
• 金额: $ 73.9万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802004%2F1
• 关键词: sarcolemmal; calcium; signalling; protein; PMCA4

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.

仅在英国就有近 100 万人受到心力衰竭的影响。心力衰竭是心脏无法再向身体组织提供足够的血液来满足其代谢需求的病症。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如何以及为何发生，以便制定更好的治疗策略。心力衰竭是在高血压或心脏病发作等心脏损伤后发生的，这会导致心肌肥大，称为肥大，然后再发展为心力衰竭。根据 MRC 之前的资助，我们确定，通过从小鼠模型的心脏细胞中删除质膜钙泵 (PMCA4) 基因，我们可以保护心脏免于肥大（肌肉肥大），并最终防止心脏肥大。 在拟议的工作计划中，我们的目标是确定 PMCA4 的删除如何以及为何能够保护心脏免受肥大和心力衰竭的影响。我们还将确定该基因是否参与心力衰竭患者疾病的发展。未来可能可以用药物来阻止 PMCA4 蛋白的作用来治疗心力衰竭患者，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能够产生这种预期效果的物质。