Signalling pathways activated by atrial dilatation and their relationship to atrial fibrillation

心房颤动（AF）是一种心律异常，影响很大比例的人群，特别是老龄化人群，并导致发病率和死亡率增加。房颤与结构性心脏病有关，尤其是与心房扩张有关。目前的治疗方法是针对症状而不是根本原因，而且大多数都有不良的副作用。我们的长期目标是研究钙释放信使肌醇（1,4,5）三磷酸（Ins(1,4,5)P3）及其直接前体磷脂酰肌醇（4,5）二磷酸（PIP2）在房颤中的作用，以期提供耐受性良好的治疗靶点。最近有证据表明Ins(1,4,5)P3和PIP2参与房颤的发生。在接下来的3年里，我们将研究急性和慢性心房扩张的细胞信号反应，并研究这些发现与临床心房颤动的关系。我们将确定参与拉伸反应的G蛋白和磷脂酶C亚型，并在房颤模型实验中使用这些研究中开发的工具。

Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and its immediate precursor phosphatidylinositol(4,5)bisphosphate (PIP2) in atrial fibrillation with a view to providing targets for therapy that are well tolerated. There is recent evidence that Ins(1,4,5)P3 and PIP2 can contribute to atrial fibrillation. Over the next 3 years we will study cellular signalling responses to acute and chronic dilatation of the atria and examine the relationship of these findings to clinical atrial fibrillation. We will identify the G protein and phospholipase C subtypes involved in responses to stretch and use tools developed in these studies in experiments with atrial fibrillation models.